ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Greg Guthrie: Hi everyone, I'm Greg Guthrie, a member of ASCO's patient education content team, and I'll be your host for today's podcast. ASCO is the American Society of Clinical Oncology, and we're the world's leading professional organization for physicians and oncology professionals caring for people with cancer. Today we're going to be talking about what patients should know about cannabis, cannabinoids, and cancer. ASCO recently published a clinical practice guideline on cannabis and cannabinoids for adults with cancer.

I'm happy to have 2 of the co-chairs from the committee that developed this guideline as our guests today. Dr. Ilana Braun is an associate professor at Harvard Medical School. Thanks for joining us, Dr. Braun.

Dr. Ilana Braun: Thanks so much for having me.

Greg Guthrie: It's a pleasure to have you here today. And Dr. Eric Roeland is an associate professor of medicine at Oregon Health and Science University. Welcome Dr. Roeland.

Dr. Eric Roeland: Thanks, Greg.

Greg Guthrie

Great. So before we begin, I want to note that neither Dr. Braun nor Dr. Roeland have any relationships to disclose related to this podcast, but you can find their full disclosures in this podcast's show notes.

So let's start with the fundamental question about this discussion, and that is what is a clinical practice guideline and how does it help guide cancer care? Dr. Roeland, can you start with this?

Dr. Eric Roeland: Of course, yeah. A clinical practice guideline describes the best practices or what clinicians call the "standard of care" with regard to a specific topic. So this is kind of the blueprint that clinicians use to guide their practice when taking care of people with cancer. And the American Society of Clinical Oncology clinical practice guideline on the use of cannabis and/or cannabinoids summarizes the best available data collected specifically from humans in clinical trials, and we combined that with a multi-disciplinary panel of expert opinion.

Greg Guthrie: Yeah, I think it's really important to always remember that best evidence comes from research in humans as well as from clinical expertise. So it's the best recommendations that we can have to support cancer care.

Dr. Eric Roeland: Greg, I also think it's very important to understand that there are different places that we gain knowledge in research. One is specifically when we are trying to figure out how a drug works, and we will test that in what we call "preclinical models," which is usually within animals. And then, once we've determined safety and efficacy, then we start taking that information and approach studies in humans. And so when our listeners are learning about new data in the use of cannabis or cannabinoids, I encourage everyone to always stop and ask, is this data coming from the animals or is this from humans?

Greg Guthrie: That's such an important point. And I think it's so essential to always look for that piece of evidence whenever you're reading about scientific advances. Alright, so let's take a moment to talk about what it means when we say cannabis and cannabinoids. Dr. Braun?

Dr. Ilana Braun: Cannabis, which is better known as marijuana, is a plant that humans have turned to for thousands of years as a medicine, in manufacturing—for instance, in the making of rope­—and for enjoyment.

It's often mistakenly viewed as having one main ingredient, tetrahydrocannabinol, or THC, but it actually has more than 300 ingredients that act in the body. Some of those ingredients are referred to as cannabinoids. There are 2 cannabinoids of greatest interest, THC, which I just mentioned, and CBD, cannabidiol. THC is responsible for the high feeling some people experience with cannabis. CBD is not.

Currently in the U.S., some cannabis products containing these cannabinoids can be sourced at the pharmacy, others at cannabis dispensaries, and some through more informal means.

Greg Guthrie: That's great. Thank you for that definition here as we continue this discussion. So what do people with cancer typically think cannabis and cannabinoids will do to help them? Dr. Roeland?

Dr. Eric Roeland: Well, it's a great question, Greg, because in clinic, when patients and their loved ones express interest in either starting cannabis or cannabinoids or are currently using them, I always want to explore what their goal of use is. And interestingly, the goals of use are far-reaching. And I have heard everything from, to help with everything, to cure my cancer. And so it's incredibly important to understand why people are reaching towards these products, to understand what their goals are. If they're focused on using this to treat the underlying cancer, or instead of standard cancer therapies, we have grave concerns about this approach. And it may lead to worse outcomes of your cancer.

However, if cannabis or cannabinoids are being used to help with controlling some symptoms during their cancer treatment, it may be helpful. And especially in one particular case where people have really bad nausea and vomiting that persists despite our best medicines to prevent it.

Greg Guthrie: Thank you for that, Dr. Roeland. Dr. Braun, did you have anything to add?

Dr. Ilana Braun: Maybe I will just point out that decisions on what to target with cannabis are often made through trial and error or in consultation with dispensaries, but not as much as I would prefer in consultation with clinical teams.

Dr. Eric Roeland: So I would also add that it's incredibly important to bring these topics up with your clinical team because although cannabis and cannabinoids are considered safe by many because they're quote "natural," it's important to recognize that they actually can interact with many of the other medications that you're already taking.

For example, patients with cancer might be experiencing really bad pain or anxiety and taking things like opioids or benzodiazepines. And when you combine that with cannabis, it can prolong some of the effects of sedation or confusion. I'd also like to point out that this is not a time where people want to try cannabis for the first time, when they are weak and/or experiencing poor appetite and higher risk of falls. This is not the best time to be trying cannabis or cannabinoids without clear guidance from the clinical care team.

Greg Guthrie: Do you find in writing this guideline and through your clinical experience that most people who are asking about cannabis and cannabinoids, that they already have been trying to use it or are considering it? Because there's a difference there, right? What goal are they looking for, and do they already have a predetermined assumption about what's going to happen with these?

Dr. Eric Roeland: You know, Greg, as clinicians, we talk about a lot of hard stuff. We talk about challenges in terms of health care, access to care, cultural differences, financial toxicity. And it's so fascinating to me that we don't talk about something as simple as whether or not patients are using cannabis. And the reality is that when patients actually bring it up in clinic, I would say that most times they're already using it and are just simply asking for some advice on how to use it safely and effectively. So once I decided to lean in on this topic and create a space for patients and their loved ones to bring it up in clinic, I have found that it's brought up during most clinical encounters.

Greg Guthrie: Fascinating. And so that's likely why the first recommendation of this guideline addresses the importance of communication between doctors and patients on this topic, correct?

Dr. Eric Roeland: Yes, absolutely. I think that doctors are reticent to talk about this topic because of concerns around legal issues, which can be highly varied across the country. And Dr. Braun can speak to this more.

Dr. Ilana Braun: Yeah, so in order to offer the very best care possible, I think that medical teams should know about all the medicines and supplements a person is taking. And this includes cannabis and cannabinoid products. Why? Well, because, as Dr. Roeland mentioned, cannabis and cannabinoids can sometimes decrease the effectiveness of some therapies that a person is on, likely including some cancer treatments, and they can also worsen side effects of other therapies. And then at the same time, cannabis and cannabinoids can be helpful in managing some symptoms of cancer and side effects of cancer treatment. So using them involves a careful weighing of risks and benefits.

So for these reasons, oncology teams really do want to be part of the conversation as someone thinks through decisions around cannabis and cannabinoids. The ASCO guidelines encourage clinicians to be open and non-judgmental and welcome transparent discussions with patients about cannabis and cannabinoids. From there, clinicians should either assist personally if they feel qualified to do so, or refer a patient to high-quality information or an advisor with greater expertise.

As for the types of information that might be helpful to share with the clinical team, a person with cancer who consumes cannabis or cannabinoids might wish to share why they're turning to cannabis, where they get their products, the active ingredients in them—so is it mainly THC or is it mainly CBD­—how they consume them, are they smoking, are they vaporizing, are they taking them by mouth, how often they consume them, what do they experience as the benefits and risks of using cannabis and cannabinoid products? Their clinicians may wish to know whether or not the cannabis products are being used as an add-on to standard treatments or whether they're being used in the place of standard treatments. And as Dr. Roeland suggested, they probably will want to know how much this practice is costing the patient each month and whether it is affordable.

I think it's especially important to speak with your clinical team if you are considering using high-potency cannabis paste in an attempt to treat cancer itself. So not just manage symptoms, but actually treat cancer itself. The reason I think it's so important to share with your cancer team is that these cannabis pastes tend to have very, very high concentrations of THC and sometimes even CBD. And I think your cancer team can be helpful in thinking through the risks and benefits of that, helping to monitor side effects that might arise.

It is commonly the case that people feel a little bit of confusion with very high doses of oral THC.

Dr. Eric Roeland: I absolutely agree. And I think these high doses of cannabis products, they're often a tincture and delivered in a syringe. And it might look like black tar. And people are told to start off with the dosing of a grain of rice. But then they're told that the dose to treat their underlying cancer can be higher than a gram of cannabis a day. In some places it's a gram and a half. This is very high dosing, and it's going to cause people to feel extremely fatigued and increase the risk of falls and being sent to the emergency department. So I want to warn people about this practice in particular, because it can cause harm. We have no evidence that it actually works.

Greg Guthrie: Thanks for that information there. I was wondering, is there a certain person on the health care team that patients should consider talking to, or anyone?

Dr. Ilana Braun: I think anyone. Health care teams keep in close contact with each other. And so this kind of information would be shared amongst the team. So lots of cancer patients begin by sharing with their infusion nurse or their nurse practitioner. They don't even need to share necessarily with their oncologist as a first step. And anyone on the team should, after these guidelines, be able to access high-quality information through their institutions.

Dr. Eric Roeland: And for those patients who might be in a location where they don't have access to an expert or don't have access to educational resources, I think one of the strengths of this current guideline is that we include an appendix, which clinicians can actually use as a 1-page handout for patients and caregivers to answer some of these most basic questions.

For example, I think there's a lot of misunderstanding about how to take cannabis or cannabinoids. And what we do see is there's a big difference between ingesting orally an edible versus smoking or inhaling cannabis. And so, for example, cannabis when eaten by mouth can take up to 2 hours to have its peak effect. And unfortunately, what happens is that patients won't feel anything after several minutes to a half hour and then stack doses to the point that they get a much higher dose than they really need. And so we really encourage people to be aware of, if it's an edible, that it can take up to 2 hours. Whereas with your breathing it in or vaping, the effects can happen almost right away.

But again, it's important to recognize that cannabis, whether it's smoked, vaped, or ingested, can be in your body for up to 12 hours and may even impact your ability to drive. So it's important that if you are going to use these tools in combination with the rest of your medicines, it's important to do it in a safe way.

Another product that is now available, even over the counter at many grocery stores, is cannabidiol, or CBD. CBD in its pure form doesn't have the euphoria associated with products that contain more THC. Most people are using this as an anti-inflammatory, or targeting sleep.

I would like to recognize that in our review of the literature, we discovered that high doses, meaning more than 300 milligrams of cannabidiol a day, actually changed the measurable enzyme levels of the liver. These enzyme levels in the liver are the same levels that we use to determine whether or not you can get your chemotherapy. So you want to make sure that you're not taking excessive doses of cannabidiol, meaning more than 300 milligrams a day, because you don't want your chemotherapy delayed because your liver enzymes might be elevated falsely from the use of high doses of cannabidiol.

Greg Guthrie: That's great, Dr. Roeland. Thanks for adding that. As an additive or part of the cancer care plan, like with all medications, we need to be aware of what we're taking and report to our health care team so we can watch for interactions and potential side effects, right?

So what are the rest of ASCO's guideline recommendations when it comes to this guideline for cannabis and cannabinoids?

Dr. Ilana Braun: So as a committee, we submitted cannabis and cannabinoids to the same level of rigorous scrutiny that we would any other aspect of oncologic care.

I can think of few other ways to validate this area of oncology science than to do so. And after an in-depth evaluation, the ASCO committee concluded that of all the reasons that a cancer patient might medicate with cannabis, the best scientific evidence supports using cannabis or cannabinoids to help with nausea and vomiting caused by cancer drugs when standard medications for nausea and vomiting don't work well enough.

Of note, ASCO guidelines make clear that there isn't evidence to hang our hats on that cannabis and cannabinoids can treat cancer itself. What's more, early evidence suggests that cannabis and cannabinoids may actually worsen outcomes for people taking a cancer treatment called "immunotherapy." Gold-standard clinical trials are necessary to confirm these worrisome findings, but for the time being, people on immunotherapy should probably best avoid cannabis and cannabinoids. I think Dr. Roeland and I and the rest of the committee have hope that more scientifically proven indications will emerge as cannabis research progresses.

Dr. Eric Roeland: Dr. Braun has also pointed out to me that there's literature and evidence supporting the use of cannabis and/or cannabinoids for the management of chronic pain not related to cancer. And this has been actually described in other guidelines, and we need to recognize that our patients living with cancer often have chronic pain that may even predate their cancer experience. However, we do not have strong evidence to support that the use of cannabis and/or cannabinoids helps with cancer pain, which is a common reason that people are reaching for these medicines.

Greg Guthrie: Great, thank you, Dr. Roeland. Thank you, Dr. Braun. So this guideline also recommends the use of cannabis or cannabinoids mainly within the setting of a clinical trial, and why is that?

Dr. Eric Roeland: Well, Greg, I think it's incredibly important for people living with cancer and their loved ones to recognize that access to cannabis has far outpaced our ability to validate and study the best methods of using cannabis and cannabinoids in people living with cancer. Meaning access has far outpaced the science that supports its use. We also recognize that just because something is quote, "natural," doesn't necessarily mean it is also safe, especially in combination with many of the drugs and cancer therapies that patients must receive while they're on treatment.

Therefore, for those of you very frustrated by the lack of evidence to support the use of these medicines in people living with cancer, you should be the first in line to volunteer for any studies that help us collect prospective evidence to demonstrate not only safety but efficacy.

I would also like to recognize how challenging it can be to perform these types of clinical trials based off of the formal designation by the federal government classifying this—cannabis and/or cannabinoids—as a Schedule 1 medicine, which creates multiple barriers for those clinical researchers who want to fully describe the safety and efficacy of these drugs. Therefore, if there is someone near you who is doing clinical research in this space, we greatly would appreciate your involvement in those clinical trials.

Dr. Ilana Braun: I agree with Eric. By participating in clinical trials, a person is doing a very kind thing for others, helping to advance the science behind cannabis and cannabinoids. Only through this controlled, systematic testing will the medical community understand whether cannabis and cannabinoids can be helpful for indications beyond the chemotherapy-related nausea and vomiting.

And we as a society need to understand whether cannabis or cannabinoids can be helpful for cancer pain, for cancer-related poor appetite, to name just a few. These clinical trials will help us move the field forward. And in terms of personal benefit, I could imagine that clinical trials might offer someone more quality-assured cannabis products, more scientifically based dosing guidelines, careful clinical observation should side effects present, and potentially efficacy. But of course there are no guarantees. That's why we're doing the trial.

Greg Guthrie: Thanks, Dr. Braun. Yeah, clinical trials are a safe way to grow our knowledge in cancer care and treatment. And definitely, as Dr. Roeland said, if we don't have evidence, the evidence in this current guideline to support recommendations, then the only way we can truly find that is by participating in clinical trials. And so I would just note that if you're interested in participating in a clinical trial, talk to a member of your health care team. And there are a number of online resources, such as ClinicalTrials.gov, where people can look for research. That's how we advance the science. So is there anything else people with cancer should know about using cannabis or cannabinoids during cancer treatment?

Dr. Eric Roeland: One key message I think for our listeners is to recognize that people have varying tolerances to this class of medicines. And what I frequently observe is that an older patient is offered an edible by their well-intentioned children who want their mom or dad to start eating more in the setting of their cancer. Unfortunately, I've experienced taking care of people that have had side effects associated with the use of cannabis or cannabinoids leading to even emergency department visits and hospitalizations.

And although these products are overall very safe and you cannot quote "overdose" on them or stop breathing because you're taking too much cannabis, it can be very uncomfortable to feel very confused and unable to stand or walk. That can be prolonged for many people, especially those who feel especially weak during their cancer therapy.

And our loved ones mean well, but sometimes the advice that they're providing could actually cause harm. And sadly, I've had many children of patients who have felt incredibly awful after their loved one had a side effect from these medicines, which actually delayed their cancer care.

Greg Guthrie: Excellent point, Dr. Roeland, thank you for that. Dr. Braun, any final notes?

Dr. Ilana Braun: Yeah, so following on Dr. Roeland's thoughts, I would also add that it's important to think about safe storage for such products, particularly if there are children or pets in the home. Cannabis products sometimes look like medicine and sometimes look like candy or baked goods. And so it's important to store them out of the reach of minors and pets.

And the last thing I'll emphasize is this: if you are living with cancer and medicating or thinking of medicating with cannabis or cannabinoids, please consider sharing this information with your clinicians so that they can help you strategize about an optimal course.

Dr. Eric Roeland: I would like to take a moment to thank the American Society of Clinical Oncology for recognizing that we need to address this important need for people living with cancer. And rather than ignore something that's happening every day in the clinic, ASCO chose to convene a panel of experts and coalesce the data and try to figure out what best practices are in this space.

And to that, I am very proud to be a member of ASCO who chooses to lean into these difficult topics rather than run away. I would also say this is a keen opportunity for everyone to advocate for more research in this space. Because talented folks like Dr. Braun, who want to do research in this space, need advocates, need participants, and need funding to fund this type of research. So again, kudos to ASCO, the members of the panel, and, of course, our patients.

Dr. Ilana Braun: Thank you, Eric, for saying that. I am so grateful to have been a part of this really cutting-edge process. And I think that clinical guidelines will help to de-stigmatize cannabis care in a meaningful way in the oncology clinic.

Greg Guthrie: This has been great. Thanks, Dr. Braun. Thanks, Dr. Roeland. If I can interject, I think one of my biggest takeaways here is every patient, caregiver, if they are or are considering cannabis or cannabinoids, the biggest question is to ask, why am I choosing this? And then to find a member of their health care team and talk to them about that. And that's how we protect each other's health and we ensure the best results possible for everyone. So I want to thank you both so much for this engaging discussion. Dr. Braun, Dr. Roeland, thanks for joining us today. And our listeners, if you'd like to learn more about this guideline, please visit www.asco.org/guidelines. Thanks so much for joining us today, and be well.

ASCO: Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

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The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this Meaningful Conversations podcast, Dr. Karan Jatwani talks to Dr. Amy Case about what people with cancer should know about hospice care, including the difference between palliative and supportive care and hospice care, who is eligible to enroll in hospice care, and the types of support available for people receiving hospice care and their family and caregivers.

Meaningful Conversations is a Cancer.Net blog and podcast series that describes the important discussions people may need to have with their providers, caregivers, and loved ones during cancer and offers ways to help navigate these conversations.

Dr. Jatwani is a Medical Oncology Fellow at Roswell Park Comprehensive Cancer Center.

Dr. Case is the Lee Foundation Endowed Chair of the Department of Palliative and Supportive Care at Roswell Park Comprehensive Cancer Center, and Professor of Medicine at the Jacobs School of Medicine and Biomedical Sciences of the University at Buffalo.

View disclosures for Dr. Jatwani and Dr. Case at Cancer.Net.

Dr. Jatwani: Hi, everyone. My name is Karan Jatwani. I'm one of the 3-year fellows at Roswell Park Comprehensive Cancer Center. I have finished my palliative care fellowship from Memorial Sloan Kettering Cancer Center. And I am interested in the integration of oncology as well as palliative care, and that is where I envision my future career to be. And it's my pleasure to be involved in a podcast with Cancer.Net and looking forward to it.

Dr. Case: Hello. My name is Amy Case, and I'm the chair of the Department of Supportive and Palliative Care here at Roswell Park Comprehensive Cancer Center, and we're in Buffalo, New York. So I appreciate being invited to speak today. And we also have a fellowship that we run here and a pretty comprehensive department with 8 divisions that include palliative, social work, psychiatry, psychology, spiritual care, bioethics, and geriatrics, and also employee resilience. So we have a lot of kind of passion projects we work on in our supportive care department.

Dr. Jatwani: Thank you so much, Dr. Case, for joining us today. I think I've always admired your work. And just to start off, just for our listeners and our audience, if you can just give us a brief idea of what palliative care is, I think that would be the best segue to enhance the discussion.

Dr. Jatwani: So "to palliate" means to make feel better. And when I talk to patients about what it is that we do, I talk about how we take care of the whole person, which includes the physical symptom management, the emotional support, which could include psychiatry, psychology, or social work support of the emotional piece. And then also the spiritual support, which often we work as a team. In order to be palliative care, you actually need to be a team. It can't just be one physician, for example, doing palliative. You need to work as a team. So generally, a core team consists of a physician, a nurse, a chaplain, a spiritual care professional, and a social worker at its core. But sometimes it can be a nurse practitioner providing that or other specialists helping on that team.

Dr. Jatwani: I think one of the key questions that always arise with the patients is, as soon as you talk about palliative care, patients start equating it to death. How do you make sure that the patients you're interacting with, how do you differentiate it with them, and how do you relieve that anxiety whenever the patient hears "palliative care"?

Dr. Case: So no matter what you call the work that we do, there will always be a stigma. So if we change the name to yellow banana, people would be afraid of yellow bananas, right? So I think that the word hospice has-- I joke that it's kind of like a 4-letter word type of situation. We call it "the H word." Sometimes patients are really fearful to hear that word. And even now, palliative has adopted this stigma. So generally, what I do is I kind of say that it's focused on quality of life. The main goal is to help people feel better, live a better quality of life, to get through their cancer treatments. And I also educate them that people who receive palliative care tend to have better outcomes. Patient-reported outcome metrics are better. So patients often have a prolonged survival. They may be able to tolerate their cancer treatment better and get through those treatments. And that generally, I would say, is something that they're happy to hear.

That's something that they're usually, "Yeah, sign me up for that." When we start with somebody-- we spend an hour with every patient for a new visit. When I start with them, they're really skeptical. Oftentimes, they're looking at me mistrustfully, like, "What is this?" And by the end of the visit, they say, "Where has this been from the beginning of my cancer journey? And why am I only getting this now? This was the best interaction I've had at this organization." And it's because we give them kind of what we call a "wrap-around care," which is almost like a big hug. We use a lot of skills that include empathy. And with our communication, we often spend a lot of time listening. And I think people really walk out feeling heard. Even if you can't solve it or cure it, you can discuss things that can just make them feel that you were there for them and you listened. And that is very powerful.

Dr. Jatwani: I 100% agree. I mean, that has been my sort of experience as well during my fellowship. I took a lot of those learnings with me when I see my patients. But also, I think coming from an oncology standpoint, I can definitely now understand that I have been at fault when I have not given that palliative blanket that you were talking about at different times. And so my question is, when can patients ask for palliative care? And we'll discuss "the H word," as you mentioned at the beginning. So we'll discuss with that as well. But when should patients undergoing cancer treatment, when should they ask for involvement of palliative care, or they should advocate for themselves or even the caregivers should advocate?

Dr. Case: Yeah. So I think that generally, palliative care, the beauty of palliative care is that it doesn't really have a time limit. Someone can ask for it anytime. And often, we encourage people right from the beginning. So there's people who may be looking for that extra added support right from the beginning. And so we usually encourage oncologists and the oncology teams to start those discussions themselves.

Dr. Jatwani: And I think at this point of time, I would like to definitely ask you. I think you mentioned "the H word" in the beginning. So can we discuss a little bit more about what is hospice care?

Dr. Case: So palliative care is provided on a trajectory. So it can be provided anytime, even for survivors, for people who are earlier in their diagnosis. But hospice has a timeline on it because it's actually a Medicare benefit that it's like almost like an insurance benefit that kicks in, but the government pays for the patient's care. And so in order to enroll or sign up for hospice, a patient has to have certain criteria in order to meet that. In order to get those things paid for. And so hospices have to—generally, it's when a patient has a life expectancy of 6 months or less, and they have decided that the cancer treatment, meaning chemotherapy, radiation in most cases, immunotherapy, the burden of that is higher than the benefit.

Most of the patients who see us in palliative are still getting their cancer treatment, and we're helping them walk the journey with them through their treatment, helping them feel better, starting those conversations. And then we do something called a transition to hospice. So many of the patients we see in palliative end up transitioning to hospice. How is palliative care different than hospice? How is hospice different than palliative care? They're very similar. The philosophy of care and the way it's provided is almost exact, meaning that it's a team-based approach made up of physical, emotional, and spiritual support for the patient provided by a team. Although in palliative care, many times that's done in a clinic or an inpatient setting. There are home palliative programs that exist. We have one here at Roswell as well. But hospice, 80% of the time, is done at home. Because generally, when people prefer to pass away and we talk to them, where do they want to be at the end of their life? I'd say 95% of people do want to be at home if that's feasible. The biggest barrier that they are worried about dying at home is that they worry about being a burden on their loved ones.

And so that's the way I frame those discussions, is that I ask them about what are the things that they're hoping for. What are the things that they're worried about? And when I find out, inevitably, like I said, it's probably the number 1 fear of people to be a burden on their loved ones. It's this wonderful thing that can reduce burden on family to help care for you and have you be at peace in the place that you wish to be.

Dr. Jatwani: I 100% agree. I think you framed it perfectly that if the discussions-- I think, as you said, they should happen at the right time point. And the other thing is I think they should happen often. They should not happen only once. They should happen at every juncture of time when the cancer care has sort of transitioned into going into the more risk and less benefit window. And that's a spectrum, as you mentioned. It does not have to happen only once, and the provider feels, "OK, I've done that discussion. Now I don't have to do it again."

Dr. Case: It's a journey.

Dr. Jatwani: It's a journey, yes.

Dr. Case: I think we always talk about a journey and that advanced care planning does not happen, excuse me, just once in the trajectory. It happens over multiple time points. And I call it "loosening the lid," where the lid is often on really tight. There's maybe often mistrust of the health care system. People are really scared. And you really need to give them that emotional support. And that's why palliative is so beautiful because we provide them that wrap-around hug when they're feeling at their most vulnerable. And then when they have comfort with us, then it's much easier to discuss these really tough topics. And I think establishing rapport, getting to know them as a human being and who they are is extremely important. So, for example, my style is to start any medical visit with a social interaction and asking them about themselves socially. I say, "Let's put the cancer aside. I want you to tell me about you. Tell me about your family. Tell me about the things that you enjoy doing for fun." And they often laugh because they want to talk just about the cancer, right? They say, "I don't have fun anymore." And then I try to ask them about the things they did before they had cancer. And you see them light up, and you see the rapport being built, and you see the trust. And once you have those types of relationships, these discussions become much easier.

Dr. Jatwani: I agree. So just to transition a little bit more about hospice care, I think you talked about that this hospice care is a Medicare benefit. Can you tell our audience, is it only at home or is it available inpatient as well? And can you speak a little bit about that?

Dr. Case:  Sure. So I mentioned before that generally, the majority of hospice care is preferred to be in the home, and really taking care of someone at the end of life actually can be less scary when you have the support of hospice. And so anyone who's in the hospital where a discussion is had and then advanced care planning is done, and they say, "You know what? I don't want to end up being on a ventilator. I'm going to elect to be a, "do not resuscitate or allow natural death.'" If that happens, I actually think it's almost imperative for hospice to also be consulted and offered. Because if you send someone home that is a "do not resuscitate" without those family support in place, the family will struggle. And so I think that it goes hand in hand. So dying at home goes hand in hand with having hospice in place. End of story. You need to have those supports in place. I do not think it will work out well for the family if you do not. And so there are rare circumstances where some physicians provide that support or home palliative can provide that support. But hospice really is the gold standard. So I'd say most of it is in the home.

But once someone enrolls in hospice, there is caveats where if a patient is having uncontrolled symptoms that are not managed by the nurses in the home and the physicians by phone or by home visit, that the patient may be able to be brought in to an inpatient hospice unit or a hospital. They can unelect—to come off of, or unenroll—in hospice. For example, they change their mind. They decide, oh, they fall they break a hip, OK? And hospice is not going to fund a non-cancer-related hip fracture repair. So they would have to unenroll from that Medicare benefit, hospice Medicare benefit, and enroll in a different part of their insurance. And it's very easy to enroll and unenroll. And so there are different parts of that Medicare benefit that pay for different things. And so if somebody gets a hip fracture, it doesn't mean they have to not have it repaired. I mean, so you adjust and unenroll them from hospice, get the hip repaired, and then enroll them back in the hospice. And so those types of things can totally be done. It doesn't mean the patient can never come back to the hospital. It doesn't mean they can't change their mind. It doesn't mean that if, say, they get pneumonia, that they can't have their pneumonia treated. So simple infections, like Clostridium difficile (C. diff), pneumonia, the hospice actually gives antibiotics.

They manage a lot of medical treatments like anticoagulation and things like that. So there are, depending on the hospice, leeway with some of those medical treatments. For example, total parenteral nutrition (TPN), percutaneous endoscopic gastrostomy (PEG) tubes, some of those things can be managed in hospice. However, if a PEG tube or a TPN is causing more burden, they will continue to have those discussions about, is this treatment in the best interest of comfort and quality of life? And so that's generally the philosophy of care. And so, yes, they can be inpatient. There can be coming back to the hospital. And there are hospice inpatient units kind of all over the country. Some cities may not have hospice inpatient units, and they have other things like something called a "comfort home," where comfort homes are depending on the area, the region that you live. Comfort homes exist in some cities where they're run by volunteers, and a patient may not be able to be at home, but they can go to a comfort home. Sometimes hospice can be provided in an assisted living where a patient's home is actually not home, it's in a facility or it can be provided in a nursing home. However, I think there's a misperception that hospice pays for the room and board of those places, and that is actually not true.

So if someone needs a facility to live, then the family or the patient is on the hook, unfortunately, for the room and board. And so a lot of times, that delays discharge. So, for example, family does not want to take that patient home. They are not able to do that. The patient then needs a facility with hospice. The assumption is the hospice will pick up the bill of the facility. So that does not happen. But hospice covers all of the costs related to the care of the patient that's related to their hospice diagnosis.

Dr. Jatwani: For patients who are living alone, who are in the elderly population, who are undergoing cancer-directed treatments, for those patients, is hospice an option? If it is, because that is always a challenging area that we face, how do you deal with those patients?

Dr. Case: That's very challenging. Generally, we would call on social work and some of those specialties to help us figure out a support care network for that patient. And so often, you can actually recruit folks to take shifts coming in and checking on that patient. And so, yes, you can have hospice care for a patient who has a care-- generally, you need to have a caregiver who is around for that patient. Ideally, in an ideal world, there's somebody with that patient 24/7 when the patient is really ill. If the patient is pretty functional and they're on hospice, walking around, there may be some hours out of the day where they may not need someone with them. And really, we kind of determine that on a case-by-case basis. I would say it's not a door-shut situation that if someone lives alone, they could never have hospice. I would not say that. But in an ideal world, we do need to recruit someone to be there with the patient.

If someone has absolutely no one to be there with them during hours during the day, which I think is pretty rare, then generally, if the person is too ill to stay home alone, it'll be a conversation that you have with that patient that they may be moved to a higher level of care, meaning that they may need a skilled nursing facility with hospice on board coming in and checking on them. That's their new home, or they may need an assisted living. And there are some facilities that provide their own hospice, meaning that if you go to that facility, they have a team that's built into that facility that provides them the end-of-life care at the facility, and they don't allow in external hospices. So it kind of depends on your area where you're practicing and asking those questions as, "Do you have an external hospice or do you provide hospice services internally?" And those are questions I often steer patients to ask.

Dr. Jatwani: Just some parting thoughts on in terms of, as you said, hospice has a very selective criteria. And some patients might say, "How can you prognosticate me for living less than 6 months?" That's a challenging question that we often get. And I think you have answered it partly, that it's enroll "on and off switch" kind of situation. But what if a patient starts feeling much, much better on hospice and they feel that they want to come back and get cancer-directed treatment, how does palliative care and hospice care come into that domain?

Dr. Case: Prognostication, when a physician is asked to prognosticate a patient, we call it "the art of prognostication" because you can't always look it up in a textbook and get the right answer. And what one physician may determine is a prognosis for a patient, another one may give a different one. Because we look at the same things, but a lot of times, there's a clinician estimate that comes into it that is really one of those, you put a bunch of facts together and you come up with what we call an estimate. And so sometimes, we may be correct. Sometimes, we may underestimate or we may overestimate.

If a patient enrolls in hospice and they, for example, are doing a lot better, they're outliving the 6 months, the hospice programs often reevaluate those patients, and they do allow folks to stay enrolled with hospice care sometimes quite longer than the 6 months. Sometimes, people are on hospice a year or even longer. What they need to document is that the patient has an ongoing need where they need the multi-disciplinary team supportive care. And so as long as you meet certain criteria, and generally, the criteria are often that they have the continuing progression of the cancer or whatever the other medical illness is, the disease itself, and advancing illness, whether that be chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF). It doesn't have to just be cancer. And you need to also have often a documentation of potentially continued functional decline or functional impairment. So prognosis is tied hand in hand with functional status. And so we don't just look at the computed tomography (CT) scan when we're determining prognosis. We look at nutritional. We look at weight loss. We look at appetite. We look at functional status and comorbidities. And there's a lot of other things that go into that, not just, "Is the tumor growing on the scan, yes or no?" So it's really important to look at a wide array of things when we're determining prognosis.

Dr. Jatwani: Yes. And I think that sort of I just wanted to give our patients some idea of how we determine. I know there are a lot, many things that we have not covered, and we haven't even touched the expertise of Dr. Case, which we hope to do that in the future. And from my end, these are the questions that I had. And we hope to reconnect soon Dr. Case, and get some more insights into other aspects of palliative care, which you have done a lot of wonderful work in.

Dr. Case: Thanks, Dr. Jatwani.

ASCO: Thank you, Dr. Jatwani and Dr. Case. Find more podcasts and blog posts in the Meaningful Conversations series at www.cancer.net/meaningfulconversations.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, the Reverend Jane Jeuland discusses what people with cancer should know about the role of chaplains in cancer care, including how chaplains are trained, the type of support they can provide for people with cancer and their family members and caregivers, and how someone with cancer can ask for spiritual support from their health care team.

Ms. Jeuland received her Masters of Divinity from Yale Divinity School. She is an ordained Episcopal priest. She received her chaplaincy training from Yale New Haven Hospital and is a board-certified chaplain. She has served as an oncology chaplain and was the first palliative care chaplain at Yale New Haven Hospital. She has no relevant relationships to disclose. 

Jane Jeuland: Hi, my name is Jane Jeuland, and I am the palliative care clinic chaplain at Yale New Haven Hospital. I'm here today to talk a little bit about what I do at Yale New Haven Hospital, and also, what is a chaplain? What is it that we offer and provide? How are we trained? And some other questions that people have for us as chaplains.

So I'll start by just describing a little bit about what I do at Yale New Haven Hospital in my role. In addition to seeing patients in our clinic, I visit with patients one-on-one through video platforms, phone, and I also visit with patients in person for scheduled appointments. And in those appointments, we get to know each other, we build a rapport and a relationship. And I help people process how they make meaning, find purpose and belonging in their lives, and how that is impacting their cancer care, but also how their cancer is really impacting their meaning, purpose, and belonging. In addition to those individual meetings, I also visit with patients in group settings. I host several groups over Zoom where patients get to talk to one another and share deeply and support each other.

And last but certainly not least, I also have started a podcast with my patients called In the Midst of It All, which you can find on Apple Podcasts and Spotify. And in that podcast, patients share their stories that they've written about their lives, about their cancer journey, and about their spirituality, and how that has helped them through all that they're going through.

So, how do chaplains get trained? I think this is one thing that people ask me quite a bit. What is your training like? Our training is pretty extensive. We need to have a 3-year Master's degree, typically a degree of divinity. And then after that, we have a year of training called Clinical Pastoral Education, CPE for short. And in that year of training, we are with a cohort of about 4 to 5 other chaplains in training. And we are supervised by a highly trained supervisor as well who has quite an extensive and long process to get certified to do that. And what our supervisors do is they help us really go out, visit with patients, and then reflect on those visits. We do things called "verbatims."

So what is a verbatim? When we write up a verbatim, we're writing up word for word an interaction that we have with a patient. And obviously, we will keep the patient confidential. But we do this with our group and with our supervisor to really kind of drill down and see where are the places that we are inserting ourselves, our own beliefs, our own needs, and how can we really better meet the patient where they are? We talk a lot about positive use of self so that we become really aware of our own self in the midst of our interaction with patients. And over the course of the year, we really learn how to focus on the patient's spirituality, their beliefs, their values, what they need in that moment.

And we're all about helping people discover their spirituality and their faith. I think sometimes a lot of people think that we might be coming in to convert someone or to make them believe a certain belief system or a certain religion. But actually, we're really here to help any patient and caregiver really figure out what it is that they believe, and how that's impacting their cancer care or how their cancer is impacting their beliefs. So that means that we do visit with people of all different faiths. We visit with people who are atheists and agnostic as well. And really, again, just try to help people discover, what is that value that you have? What are your beliefs? Where do you find meaning, purpose, and belonging?

And so what are some things that come up as we meet with patients? I, again, work in palliative care in the clinic settings. I'm outpatient. But a lot of chaplains work inpatient in a variety of settings. And so you'll have chaplains in a medical intensive care unit (ICU), or you'll have a chaplain in an infusion suite or on a floor as well. And so we see patients at all different stages. We see patients who are just newly diagnosed and have a cancer that's highly treatable. We see patients who are doing really, really well on their treatments. And we also see patients who are starting to kind of struggle with lots of symptoms, pain through sometimes months or years of cancer treatments. And then on the other end of this spectrum, we see patients who are very advanced in their cancer, have a terminal diagnosis, and we really see them through all that that entails, the outpatient visits as well as the inpatient, and even as someone comes to the end of their lives.

And so what can come up in our meetings as I meet with patients? When someone's diagnosed with a terminal diagnosis, there is a lot of discussion about fear of dying, what happens in the process of dying, and then also, of course, what happens after we die? What is there after we die? Is there anything after we die? Or what is the afterlife like? And so often, again, I try to help people really reflect on what they may think the afterlife is like, if there is one. And then we have rich discussions around that. For kind of that big question of what happens as we're dying, that's when I like to pull in other members of the team. But certainly, chaplains can help process that as well. We also really do help people articulate their thoughts about the divine and whatever name they give to the divine. And often, what I hear in my appointments is not so much, "Is the divine as God giving me this cancer?" but, "Why would God allow it?" So as I talk with folks, folks will say, "I really believe in a loving God and a God that heals and a God that helps us. Why would a God like that allow me to have this cancer? Why would God allow my loved one to have this cancer and for their lives to be taken far, far too soon?" And for that, it's a tricky one. We, as chaplains, don't have a pill that we can give you and send you home and say, "OK, here's your prescription. Take that, and you'll get all the answers to why would God allow this?"

So it's really a process of talking through this. It's a process of kind of discovering a little bit more about what we believe God is, what the patient believes about God, and God's character in the midst of it all. And it's also just sitting in the mystery of it that we don't know. We don't know why a loving God would allow this, why a God that heals would heal some people and not others, why a God who heals would heal at this point in your life, and then not at a different point in your life, and why this happens at all. And so chaplains don't rush quick to give advice. We allow sitting in that grief, in that suffering, in the sorrow.

But then again, as we talk about who is God for this person, I also like to help people see, OK, if God isn't healing right now, if we can't understand why God is allowing this to happen, where is God in the midst of it? And this is what I love about my job so much is that I hear from such a variety of faiths and people of different values and spiritualities, how they do see the divine working in their lives. And so for some, "I have a lot of pain, but I know that God is with me, and I don't feel alone in this." Or, "I was feeling grief and loss over a loved one and wondering what my afterlife's going to be like as I face the end of my life and I was having this turmoil. And all of a sudden, I felt this deep, deep, deep peace wash over me. And I feel like that might be God." Or for someone who maybe doesn't have a particular religion, they may say, "I know that the love of my family and friends is so powerful. It's helping me through this. It's getting me through the dark times. And I know that that is what holds us together. And it's more than just what we can see and taste and feel, that that love is something greater and bigger." So it's really rich conversations like that that I get to have.

I think also some other topics that come up is cancer is grueling. Cancer, it can be long. And there are things, people talk about scan anxiety. Of course, the side effects and physical pain. I hear a lot about insurance and how that's just so difficult and such a struggle to get on the phone, talk about insurance when time is so precious and so short. And for others who are healing from cancer, it sometimes is a lot of conversation about, "Well, how do I get back to life? And I used to do this amazing job, but I don't think that I can do that anymore. I don't have the stamina. I don't know how I would be able to do that job." And so I help people process that a lot. And again, that goes back to how do we find purpose in life, that meaning, purpose, belonging. And a lot of us find our purpose in work, in what we do. And so chaplains can help people through topics like that as well.

And for survivors, we're always so happy in our palliative care clinic to help people heal. A lot of people think palliative care is just end of life. It is not. I have a lot of survivors I meet with, and they'll talk about kind of always looking over their shoulder. Is it going to come back? And finding a way to give back and to help other patients. And that is something I really love helping people with is, how do we give back? What are some ways to help others after I've had cancer? How can I help people?

And so I have to say, I've been really, really privileged in my work as I meet with patients and individually in groups and help them write their stories and read their stories and interview on the podcast. I've just been so, so struck by all of the beauty, the resilience, the strength that I hear, the really depth and the richness of people's spirituality as they go through cancer care and really do some hard work to unpack and process all that's going on. And some of the common themes that I've heard is people will talk about how cancer has completely changed their perspective. And so people will talk about how before they had cancer, they were focused on their wonderful job, but also the pay and making sure they get ahead and can have stuff, that newest car or that bigger home. And when they have come through cancer and all that that entails, they start to think, "Gosh, you know what? I like those things, but what's much more important is the people that are right in front of me. It's the things that are free. It's time. It's talking with a loved one. It's really sharing deeply what's on your heart and mind, knowing that time is precious."

And so I really am so struck by some of the things that people will share with me about their loved ones, their caregivers. If you are a caregiver, you know that you are loved, and that everything you're doing is really helpful and so, so appreciated, and that the time that you spend together and the things that you're able to share is so important. It doesn't have to be a big trip or people think about bucket list things, and it doesn't have to be all that. It's sometimes just that conversation over coffee or as you're going to sleep at night, those words that are shared are so important. And so people's perspectives, I think, really do shift and change and deepen. And people also find God in the midst of everything that they're going through.

I had a patient who heard stories on the podcast and said, "I really want to write my own." So we worked together. And we talked a lot about her faith, and she wasn't really sure what to believe. She had had a hard time growing up in terms of her spirituality. And through her writing, and also through her cancer journey, she was able to really articulate her sense of God as a loving companion to give her peace, not one that's punishing, but a God that's loving. And now, as she comes to the end of her life, she's really finding a great more deal of peace, thinking about God and knowing that God is with her. I think as I share stories like these, though, I'm always so mindful, too, that I think in our culture, we think a lot about things being 5 easy steps. You can do this, and you can get better, and you can find insight and meaning in 5 easy steps. And it's really not that. It's really a process. And so as you hear stories from other cancer patients who may be in that place of peace and accepting and belonging and you're not there, also know that they were not there at a certain point and that it is a process, and it does take time. And so, again, that's what chaplains are really here for. We're here to help unpack a lot of that, to help people process that.

And so you might be actually wondering, "You know what? I am going through a lot of cancer care here where I am, and I really would actually like to talk to a chaplain. How do I do that?" So the best way is to simply ask for a chaplain. We're most often called chaplains, but sometimes we're called spiritual counselors, spiritual care providers. So maybe a different term where you're located. But you can ask a nurse, your oncologist, anyone on the team, your social worker, to contact a chaplain. There are different levels of care in different settings. So you may have a chaplain in an outpatient setting, but maybe not. And so most likely, most hospitals have inpatient chaplains. If you are outpatient, though, and you really want to talk to a chaplain, I still encourage you to ask for one. And in that case, call the spiritual care or chaplaincy department directly, and you should be able to do that through your information line in your hospital. But in the hospital, for the most part, the hospitals have inpatient chaplains. Many have 24/7 on-call chaplains. And so always don't hesitate to ask the nurse, and we're happy to come by.

We also do provide support for families. And so this is something that we do quite often, especially in the inpatient setting, in an ICU setting, at those times when decisions are being made. What should we do? What we often call in our hospital setting "goals of care" conversations. What is the goal of care here? Are we going to continue with aggressive interventions? Are we going to start to move to aggressive comfort care? And so chaplains help talk through that as well. So you can always call or ask for a chaplain when you're inpatient, certainly when those decisions are being made. And we're there for you as a patient, but again, we're also there for your caregivers, your loved ones. And in those settings, we're often meeting with families sometimes outside of the room even. And we help your loved ones process as well. Just like I've mentioned, all the other things that I help patients process, we also help caregivers with a lot of those topics. In addition, of course, for a caregiver, we sit with them in the pain and the suffering and the loss and the anxiety, and talk through their ways that they find meaning, purpose, and belonging, and how they're processing all that's going on with their loved one, who's the patient.

I've heard from more than one patient that they say, "I feel like as hard as cancer is, it's easier on me than it is on my loved one. I hate to see what they're going through. I sometimes feel like a burden." But whenever I talk to a caregiver about that, they always say, "Absolutely not. You're not a burden. I wouldn't want to be anywhere else in the world." If they're sitting there in the ICU, long hours, surviving on coffee, very little sleep, lots of interruptions, sleeping in a chair beside your bed. Every single time, those caregivers will say, "I would not want to be anywhere else in the world. I want to be here. This is what I want to be doing." If you're the patient, feeling like a burden, know that more often than not, your loved one is really wanting to do what they're doing.

But caregiver burnout is real, too, especially if your care is going on for a long, long time. And so chaplains can help caregivers process that burden. And we also work with the team, sometimes social workers and others to find support systems so that if they need help, so that they can just have a moment to themselves, go for a walk, that we can help them think about resources that may be their faith community, their church, their synagogue, their mosque, their faith community can come and help give that relief or that respite for them, but also other resources in the hospital. So you may have an integrative medicine component.

So I hope that you've been able to learn a little bit more about chaplains, about how we're trained, about what we typically hear from patients, and what we can provide support around. How we also support caregivers. We are inpatient, we are outpatient, we are 24/7 most often, and how you can get in touch with a chaplain. I really encourage you to reach out to a chaplain. We're always happy to help. It's what we're here to do. So thank you so much for having me on the podcast today. It was really a delight to be here. And I hope you have peace. I hope that you find strength, meaning, purpose, and belonging in the midst of it all.

ASCO: Thank you, Ms. Jeuland. Learn more about the role of chaplains at www.cancer.net/palliative.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Fay Hlubocky  and Shelly Rosenfeld discuss what people should know about returning to work after cancer treatment. This podcast is intended for informational purposes only and does not constitute legal or medical advice. 

Dr. Hlubocky is a licensed clinical health psychologist with an expertise in psychosocial oncology and a health care ethicist at the University of Chicago. She's also the Cancer.Net Associate Editor for Psychosocial Oncology.

Ms. Rosenfeld is the director of the Disability Rights Legal Center's Cancer Legal Resource Center, which provides free information and resources about cancer-related issues. 

View disclosures for Dr. Hlubocky and Ms. Rosenfeld at Cancer.Net.

Claire Smith: Hi, everyone. I'm Claire Smith, a member of the Cancer.Net team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient education website of ASCO, the American Society of Clinical Oncology. Today, we'll be talking about what people with cancer should know about returning to work after treatment, including information about the legal protections available to people with cancer in the United States. Our guests today are Dr. Fay Hlubocky and Ms. Shelly Rosenfeld. Dr. Hlubocky is a licensed clinical health psychologist with an expertise in psychosocial oncology and a health care ethicist at the University of Chicago. She's also the Cancer.Net Associate Editor for Psychosocial Oncology. Thanks for joining us today, Dr. Hlubocky.

Dr. Fay Hlubocky: Thank you, Claire. It's such an honor and a privilege to be with you and Shelly today.

Claire Smith: Wonderful. Our next guest, Ms. Rosenfeld, is the director of Disability Rights Legal Center's Cancer Legal Resource Center, which provides free information and resources about cancer-related legal issues to members of the cancer community across the U.S. Thanks so much for being here, Ms. Rosenfeld.

Shelly Rosenfeld: Thank you. I'm honored and grateful to be here today.

Claire Smith: Before we begin, I should mention that Dr. Hlubocky and Ms. Rosenfeld do not have any relationships to disclose related to this podcast, and you can find their full disclosures on Cancer.Net. So, to start, Dr. Hlubocky, can you talk a little bit about some of the ways that people might think about work differently after an experience like cancer?

Dr. Fay Hlubocky: Thank you, Claire. That's such an important question to start today's talk with. For many, the thoughts and decision-making surrounding returning to work can be very complex. Perspectives on if, how, and when to return to work will differ from person to person. Although one may feel quite motivated and even inspired to return to work after the cancer experience, the idea to return to work immediately after this post-cancer journey phase may simply seem overwhelming and bring about anxious and worrying thoughts. Thoughts and questions such as, "Am I ready to return to work after all I've been through?" or "Can I do the job like I did before?" are common and expected.

For some who may experience financial burdens, these individuals feel compelled to return to work with thoughts of, "I have to get back to work," and feel like that's the only option is to return to work immediately even if not ready. Yet others may ask themselves, "Should I work full- or part-time? How can I return to work?" Or, "Can I return to that same busy schedule as I had engaged in before?"

Finally, some may wonder if that same job is right for them after all one has been through. Again, these are very normal, common, and expected thoughts and questions regarding return to work that the individuals certainly may hold after the cancer experience.

Claire Smith: Wonderful. Thank you for that overview. And next, you touched on some concerns, but I'd love to hear about what concerns someone might have about returning to work after cancer. Let's go to you, Ms. Rosenfeld.

Shelly Rosenfeld: Well, one concern for someone returning to work, it could be either, of course, returning to their job, but it can also be returning to work and starting a new job. And that might be when one might need to perhaps take additional days off, and whether it's for treatment or follow-up care or perhaps just monitoring as well. But to use up those sick days and then to need additional sick days, there is protections out there such as Family and Medical Leave Act, or FMLA. But a concern for someone starting a new job is, in order to be covered by FMLA or the Family and Medical Leave Act, someone has to have worked for the employer for a total of 12 months and have worked at least 1,250 hours in the last 12 months, which comes out to a little more than part-time. But that is certainly a concern because taking time off whether to care-- actually, it could also be a caregiver taking care of someone with cancer, that they need to have worked for that employer for at least 12 months.

Later, I think we might be talking about one way to work with the employer in terms of - just to kind of hint with the Americans with Disabilities Act - kind of a creative way to ask for additional time off and to see if that can work out with the employer. So I want to wait until we talk about that a little more in depth, but I just want to say there is hope and there is something that perhaps can be worked out with your employer if there is that concern. But I just want to say that while FMLA, and just to kind of briefly touch upon it, it allows certain employees to take up to 12 work weeks per year to take care of oneself or certain family members with a serious health condition. For example, that could include a spouse, parent, or child. So it is unpaid, but one's job has to stay open for that person until the end of that 12-week period, and the employer has to keep providing health benefits. So it's something to keep in mind if somebody is returning to work and is at their job now for some time and needs to take those days off. Beyond those sick days, there are protections out there.

But if they're just returning to work and they haven't been at a job for that long, then they should consider, "OK. Maybe the state has additional protections that the federal law does not have," or to think about-- and we'll talk about reasonable accommodations in Americans with Disabilities Act in a bit, I think, as a solution. So with every challenge, I think there is some kind of option, but that is certainly a concern.

Claire Smith: Yeah. Absolutely. I think it's so important to sort of think about these concerns as people are going to worry about them, but there are ways to sort of address and hopefully cope with them. Dr. Hlubocky, do you have anything else to add?

Dr. Fay Hlubocky: I agree, many survivors we know with cancer do desire to return to work. Just recognizing the fact that holding a job provides a routine, a schedule, freedom, income, meaning, it makes us feel fulfilled, it gives us a sense of purpose, and work specifically for survivors can bring a sense of normality, especially after that cancer experience. Yet for others, we know that the thought of returning to work can be very concerning. Folks might be worried over their energy and their endurance and ability to really perform at their job due to continuing or existing cancer-related or treatment-related symptoms, such as fatigue or insomnia or pain. Others may worry about colleagues' attitudes and relationships, concerns and fears over if colleagues will judge them for their appearance or their performance may arise. As well, many survivors question, "How will I be treated?" or "Will they work with me as they did before?" These are also frequent and commonly held concerns by many patients and survivors.

For all survivors, it's important to recognize that this is a new normal, a new phase in this journey post-cancer and cancer treatment that can really bring a new perspective with greater meaning and purpose. This new perspective - really, this growth - can be a motivator and inspire not only you in the work environment but your colleagues as well.

Claire Smith: So talking about maybe some of the things that we can share with our listeners to help assuage some of these concerns that they may have. I want to start, if someone is applying for a new job after cancer treatment, maybe they've been out of the workforce for a little while while going through cancer and its treatment, are there any legal protections available to them during that process, Ms. Rosenfeld?

Shelly Rosenfeld: There are. So I briefly mentioned the Americans with Disabilities Act, or ADA, which is a federal law that makes it illegal for employers with 15 or more employees to discriminate against, and it includes qualified job applicants or qualified employees with disabilities in any stage of the employment process. So that includes the interview process. A lot of people don't know that before someone even starts working, that they do have those protections. So that is really important for someone to keep in mind as they go through the interview process.

So an employer is not allowed to ask about a job applicant's medical history, whether they've taken any leave in the past, or whether they expect to take leave. The only 2 questions related to disability or cancer that employees are allowed to ask are, "Are you able to perform the essential job functions?" and "How will you perform the essential job functions?" So, in order for someone to receive protection under the ADA, they have to be able to do the essential job functions.

For example, without anyone knowing me, I don't have experience playing football. So, I do not have the ability currently to do the essential functions of being an NFL football player, not at this time and not in the past, so far. So, for example, the ADA, no matter what, wouldn't protect me because I can't do those job tasks. But if someone can do the essential functions of a job, right, they're applying for it, hopefully they're able to do those essential functions, if they have cancer or are affected by the effects of cancer treatment, they could be protected. So it is really important to keep in mind during that job application process, the employer can't ask if you're disabled. I know that sometimes they'll have things on the end of an application, but those are optional, right? So someone does not have to answer that, but they can ask, of course, if you can do the essential functions of the job. And so, yeah, I think that's just something to really keep in mind as someone's going out through that process.

Claire Smith: You talked a little bit about the ADA and how we can use those protections. And a lot of people with cancer, they may have mental changes like brain fog or even physical changes, fatigue, or other side effects, long-term side effects of their cancer and treatment, where they might need some accommodations to be able to accomplish those essential job functions that they can do. Can you talk a little bit about what that process looks like to ask for those accommodations?

Shelly Rosenfeld: Just to recap, cancer, the effects of cancer can be a disability under the Americans with Disabilities Act. I know for some people affected by cancer, thinking of the word "disabled" as it relates to cancer might be just a new way to think about it. So I'm only talking legally. So somebody might have been in the best health of their life and been in the best shape and then they're affected by cancer, and then the law may consider them as disabled. So we're talking about disability in terms of the legal definition for the Americans with Disabilities Act.

 So let's talk about reasonable accommodations. So as you mentioned, of course, the effects of cancer can be a disability because they might substantially impair major life activities such as eating, sleeping, concentrating. And so reasonable accommodations can range anywhere from making changes to a physical environment, such as moving file drawers to a more accessible location, or changes to the way that someone works. For example, teleconferences into meetings rather than in person.

Whether an employer has to give someone the type of accommodation they're trying to get depends on whether giving it would be an undue hardship to the employer. Being an undue hardship usually means practically that it will cost the employer too much to give someone the accommodations, so what costs too much really depends on the specific job and the specific employer at issue. So, for example, what might be easy to do for one employer may actually be really difficult for another, but we usually ask for folks to ask for accommodations before their work performance starts to suffer. So if your performance suffers at work, an employer may take negative action against you if they don't know you have a disability or a need for accommodation. So if an employer sees someone sleeping at their desk, they can be fired. So if the employee decides to ask for a reasonable accommodation under the ADA and tells the employer that they have fatigue from cancer treatment and need more frequent breaks due to fatigue before the employer has a chance to see them sleeping on the job, the employee has more protection at work.

It is a personal decision, and I just want to touch upon this because this question sometimes comes up where people say, "Should I talk to my employer or not?" I know, the CLRC, we don't take a position, yes or no. It is completely that person's decision, and I would respect someone either way. So that might on the one side be a little nerve-racking, but it could also on the flip side be reassuring. But there's no wrong choice. It's best to do what is best for that person. I do recommend, however, if you do want to have that discussion with your employer, if you can find someone trusted, whether it's a parent or a friend or just even a doctor or patient navigator, and try to have that conversation, because it can be difficult talking to an employer about that. Even if you feel like you really have a good relationship with that employer, it is still a different type of discussion. And I just want to also mention that it is an interactive process. So suppose someone asks for accommodation, a reasonable accommodation under the ADA, and the employer says, "This is not something that we can do. It's going to cost too much. It's not practical." Then hopefully they come back with something and say, "How about this option?" And then the employee could say, "It still doesn't really help what is the ultimate challenge here. How about this?" And hopefully it's both sides working together in the interactive process. Now, of course, if someone asks for a reasonable accommodation, it may very well be granted in its original request. But just to keep in mind that if an employer pushes back, it is designed to be reasonable for both sides.

And just to give an example, because I think it could be hard when someone says, "It depends on the employer. It depends on the employee." Right? So many people have such different jobs and employers are also so different, but here's an example. Suppose, for example, someone is a cashier, and they have to interact with people. They have to ring them up and take money and work at the cash register, but they're going through cancer treatment. And they're still able to work, but they do need a reasonable accommodation. So, for example, they might ask for a stool to sit between helping people. So if there's not someone else next in line, they can at least sit down. Giving them a separate office with a gold chair might not be reasonable, because they actually have to be there to help folks, but a stool doesn't take too much space, gives someone the opportunity to sit down, could very well be reasonable. So that's just kind of a way to think about it as an example.

And I think the doctor or also patient navigator team can be partners in this. You can ask, "When someone has this treatment, what side effects can I expect? I do this as my job. Have you had patients like this in the past? What are some things that might have helped them?" And you just start that conversation going and also think about your job and how you go about your job and what might help, or how you're feeling and what could really make a big difference. It might be that snacks are not allowed at the desk, but having a snack and being able to eat it can really combat nausea. It can also be more than one accommodation. There might be more than one side effect that needs to be addressed.

So it is something to keep in mind. Be aware of yourself and what helps you ultimately succeed so you can keep having that income, keep having that job, and hopefully keep having that health insurance. Of course, there's the FMLA protections if someone needs to take that time off, but that is something to keep in mind. And because I promised this, I just want to raise it now, is that if someone is not eligible for FMLA based on they haven't worked at their job long enough to qualify and there's no additional state protections that apply, they may be able to ask for some additional time off under the Americans with Disabilities Act beyond their sick days. Saying, "I don't know when I'll get back," and kind of an indefinite time of leave, that might be harder to get approval for as a reasonable accommodation. But saying, "I need X number of days, and then I'll check in with you about that." Or, "I need X number of days," might be something that the employer might be more willing to work with that person. So like I said, there is something to be worked out potentially.

Claire Smith: Oh, wonderful. Thank you for outlining all of that. I think that's really helpful to sort of understand what that process looks like, what maybe some reasonable accommodations are, and the fact that it is sort of an interactive process.

So another thing that Dr. Hlubocky mentioned earlier as maybe being a concern is how to talk to coworkers. Are there questions that coworkers might have after you've been out for cancer treatment, how to manage perhaps uncomfortable conversations. Can you talk about some of the ways that someone with cancer can kind of help prepare mentally for those kinds of conversations, Dr. Hlubocky?

Dr. Fay Hlubocky: Reactions will be different, and they'll vary from person to person, colleague to colleague. Some colleagues will be supportive, know when to ask or not to ask questions, and these colleagues will also try to be helpful with tasks as you return to work. Yet others might be very avoidant because they simply don't know what to say, and that can be hurtful because we all want to feel supported by our colleagues, especially after an experience like cancer. Therefore, it's important for you to prepare and plan on what you want to say before you're returning to work.

Honestly, there's really no right or wrong way to address this, as everybody deals with the cancer experience differently. You may desire to talk openly about the cancer experience, or you might wish to simply move on in order not to be treated differently by colleagues. Empowering yourself by setting boundaries on how to address these questions is key. For example, you can thank your colleagues for their concerns. However, express that, for you, now is not the time or the place to discuss your experience. Remember, you have to feel comfortable and safe in discussing your experience.

Accept help if offered, especially in the initial stages of returning to work. Also, it's important to be prepared that some relationships may change. For example, those who were supportive and close to you before the cancer may distance themselves afterwards. You will learn who you can count on, and that is what's important. If you do feel comfortable, talk to your supervisor regarding any concerns that you may have about returning to work and addressing colleagues' questions so the supervisor can also help prepare the staff as well. But, again, only if you are comfortable. Be sure to check in with your supervisor, especially if you feel that the work environment is not supportive.

Claire Smith: Wonderful. Great advice. And working can sometimes be stressful under the best of circumstances, and especially if you've gone through cancer treatment, you're maybe starting a new job or returning to a workplace. What are some tips for coping with some of those emotions and stresses that might arise?

Dr. Fay Hlubocky: First and foremost, it's talking with your oncology team about when is the best time to return to work given your specific phase in the cancer survivorship journey, as well as inquiring about symptoms that you may have, like fatigue or cancer-related cognitive dysfunction and any other worries or symptoms that may interfere with returning to work. We want to be sure that you're physically healthy to return to work, and be sure to talk to them about any fears associated with working. Remember, we, your cancer team, are here to help you. Also, knowledge is power, and thus education on what is needed or how to return to work after cancer, taking into consideration life changes and symptoms can help to alleviate some of this distress. Also, again, if comfortable, talk to your supervisor about your options and to determine a plan. With the change in work environment, you may have the option to return slowly, gradually to the work environment first, maybe virtually, then part-time with fewer hours and gradually full-time. Again, if comfortable, talk to your supervisor about any time and work accommodations you may feel.

Planning this return to work in partnership with your supervisor can really help you prepare as well as address any worries and anxieties you may hold. If the stress and the anxiety associated with returning to work is just really simply too overwhelming, talk to your therapist to help you plan to return to work. If you're not already connected to psychosocial support, engaging in the service can be a really valuable tool to help you determine your readiness to return to work. A psychologist, a social worker can really help you with preparing and problem-solving and planning when or if returning to work is an option now or in the future. Cognitive behavioral therapy, or CBT, is a research-based psychotherapy that we use that can help to address anxious and worried thoughts that you may have. And the goal of CBT is really to learn to control, challenge, and overcome distressing thoughts and beliefs about returning to work and helps you learn skills to really change your behaviors.

It's also OK to realize that your job is now not right for you. Remember, a comprehensive plan in collaboration with your doctor, potentially your supervisor and psychosocial support, can really help prepare you, empower you as you begin the process of returning to work.

Claire Smith: One other thing I wanted to touch on a little bit is issues around workplace discrimination. If someone is worried that they might face workplace discrimination after cancer, are there any resources available to them, Ms. Rosenfeld?

Shelly Rosenfeld: Yes. If someone believes they've been discriminated against in the workplace or have questions about anti-discrimination protections, first of all, the Cancer Legal Resource Center, or CLRC, we have handouts on our website about someone's right to be free from discrimination in the workplace. Our website is thedrlc.org/cancer, and we recommend that someone speak with an employment attorney to discuss their legal options if someone thinks that they've been faced with discrimination. Someone also might want to file a complaint with the Equal Employment Opportunity Commission, or EEOC. The person can bring a claim for a violation of the Americans with Disabilities Act, or ADA, file a complaint with their state fair employment agency - of course, that depends on the person's state, where they live and work - or file a lawsuit against their employer. So, there's also an organization called the Job Accommodation Network, or JAN, which is a service of the U.S. Department of Labor's Office of Disability Employment Policy, where someone can learn more about resources available to them.

So certainly, there are different options. We hope that no one experiences discrimination because of cancer, their history of cancer, an association with someone with cancer. Hopefully, no one ever experiences that. But if they do, hopefully they feel empowered already that there are options out there for them to assert their rights and hopefully ensure that others in the future will be free from discrimination as a result of cancer in the workplace.

Claire Smith: Thank you for sharing those resources. Absolutely. Do either of you have any final thoughts before I let you go today or anything else you wanted to touch on for our listeners?

Shelly Rosenfeld: I just want to say that, at times, it can be overwhelming, in addition to having a cancer diagnosis, to encounter so many different legal issues that are kind of these non-medical side effects of cancer. And I just want to say that at the Cancer Legal Resource Center, and I know that patient care teams really do care about keeping someone informed of their rights, and so it is important to know that there are rights out there and not to be hopeless about their rights because there might be things that you just never knew were possible. But just by making that effort to learn more about what's out there and what you might be entitled to, whether it's a health insurance appeal, whether if someone has to take a longer time off their job more than a year because of cancer, that there are income replacement options potentially through Social Security, that there are just health insurance options potentially out there for them, that there is hope and it is worth trying. It is worth appealing. And to work with your doctor and medical team saying, "Can you give me a letter? Can you write this for me? Do you have something that you've submitted for someone else for appeal for this medication or for this type of treatment?" And try to seek support in a practical way to stand up for yourself because the results and the upside of doing so are so important.

So I just hope that someone comes away with this knowing-- you don't have to memorize or take notes or be an expert to know this after this podcast, just know that it's out there and that there are resources, and you can learn. And what the CLRC does, we do free. So just to know that there is something out there for them.

Claire Smith: Wonderful. Great message.

Dr. Fay Hlubocky: That's great, Shelly. Thank you. I've learned so much from this podcast. And to all the Cancer.Net audience out there, whether you're a patient or a caregiver or even part of the team, please know that we're here to help you in any capacity. Don't fight this alone, have self-compassion, be patient with oneself. This process does take time, and there's lots of resources here to help you to decide if returning to work is right for you now or in the future. Again, we're here to help you.

Claire Smith: I love that. Thank you. And thank you both so much for sharing your expertise today. It was really wonderful having you, Dr. Hlubocky and Ms. Rosenfeld. Thanks for joining us.

Shelly Rosenfeld: Thank you.

Dr. Fay Hlubocky: Thank you so much. It was an honor and a pleasure to be with you all. Thank you.

ASCO: Thank you, Dr. Hlubocky and Ms. Rosenfeld. You can find more resources and information about life during and after cancer treatment at www.cancer.net/survivorship.

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The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, members of the Cancer.Net Editorial Board discuss the latest research, innovations, and discussions taking place across the field of genitourinary cancers, including prostate cancer, bladder cancer, kidney cancer, and testicular cancer.

This podcast is led by Cancer.Net Associate Editor for Genitourinary Cancers, Dr. Petros Grivas. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine and a professor in the clinical research division at the Fred Hutchinson Cancer Research Center. He is joined by Dr. Neeraj Agarwal, Dr. Shilpa Gupta, Dr. Tian Zhang, and Dr. Timothy Gilligan.

Dr. Agarwal is a Professor of Medicine, and a Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute at the University of Utah. He directs the Genitourinary Oncology Program and Center of Investigational Therapeutics at the Huntsman Cancer Institute. He is also the Cancer.Net Specialty Editor for Prostate Cancer.

Dr. Gupta is the Director of the Genitourinary Medical Oncology Program at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. She is also the Cancer.Net Specialty Editor for Bladder Cancer.

Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. She is also the Cancer.Net Specialty Editor for Kidney Cancer.

Dr. Gilligan is a Medical Oncologist, Associate Professor of Medicine, and Vice-Chair for Education at the Cleveland Clinic Taussig Cancer Institute. He is also the Cancer.Net Specialty Editor for Testicular Cancer.

 View full disclosures for Dr. Grivas, Dr. Agarwal, Dr. Gupta, Dr. Zhang, and Dr. Gilligan at Cancer.Net.

Dr. Grivas: Hello. I'm Dr. Petros Grivas. I'm a medical oncologist in Seattle, a professor at the University of Washington and Fred Hutchinson Cancer Center. I'm really excited and thrilled today to host wonderful superstars in the field of GU Medical Oncology who will share insights about the highlights of kidney cancer, prostate cancer, and bladder, urothelial, urinary tract cancers that happened in 2023. And this highlight aims to inform our great audience about what are the clinically relevant insights, what patients should be aware, what patients should ask for when they go to the clinic, or overall, how they can be most well-informed and have the necessary tools to improve their care and feel well-supported in regards to education. So without further ado, we're going to cover in first prostate cancer, a very important update in this year. So all the people out there that are interested in hearing about prostate cancer will find this very, very useful and insightful. I'm very excited to host Professor, Dr. Neeraj Agarwal from University of Utah. Neeraj, do you want to introduce yourself?

Dr. Agarwal: Of course. It's such an honor to be here. My name is Dr. Neeraj Agarwal. I'm a professor of medicine and director of genitourinary oncology program at the University of Utah Huntsman Cancer Institute.

Dr. Grivas: Neeraj, thank you so much for accepting the invitation and being with us. I would like to ask you, what's your take on the current state of genetic testing in patients with prostate cancer? And when we say genetic testing, maybe you can clarify the distinction between germline and somatic and comment on both if you could. Thank you.

Dr. Agarwal: Of course, a very important topic. I must tell you that it is very clear from all the guidelines that in patients with advanced prostate cancer or metastatic prostate cancer, meaning when prostate cancer has spread to different parts of the body, both germline testing to look for hereditary mutations in the DNA repair genes and testing for the same genes inside the tumor tissue are considered standard of care. So, a patient with advanced prostate cancer should have germline testing and somatic tumor tissue testing to look for mutations that can predispose them to have prostate cancer, and if they have genes in the tumor which can be targeted by the current approved drugs, like drugs which are already approved right now or which are in clinical trials.

Unfortunately, less than 50% of patients in many areas of the country and in the world, less than 20% of patients are being tested. And even more, unfortunately, patients are less likely to be tested are those who are not well-resourced, who are not living in rich countries, if you will. They are poor- or low-resourced countries. Even with high-income countries, within those countries, patients who are living in relatively not-so-affluent neighborhoods, they are less likely to be tested. From racial perspective, patients who are Black or who are Hispanics are less likely to be tested. Based on how many drugs are out there in the clinic and emerging through clinical trials. And the fact that we can use many of these mutations for prognostication, to inform survival, to inform aggressiveness of the disease. It is not only to treat those patients, but also how to monitor the disease. The genetic testing is very important.

Dr. Grivas: Thank you so much, Neeraj. It's very insightful. And I think you did a great job outlining the clinical relevance for both the patient in terms of treatment decision-making and therapy options, especially for advanced prostate cancer, as well as the broader family and implications for cancer prevention and cancer screening for the broader family members. So definitely a very important topic.

Neeraj, the other question I have, if you could tell us more about this class of medications called PARP inhibitors. If you can comment on the currently approved PARP inhibitors, either as a single agent, what we call monotherapy or combination therapies for patients with prostate cancer in the United States, and who is eligible to receive those therapies?

Dr. Agarwal: And this is such a nice segue to talk about PARP inhibitors as we were just talking about genetic testing of prostate cancer. So, PARP inhibitors are a class of drug which are instrumental, critical in treatment of patients who harbor mutations in those DNA repair genes. And two monotherapies, meaning using these PARP inhibitors as single agents have been already approved in the United States and several other countries. These are olaparib or rucaparib. Olaparib is approved after patients have had disease progression on novel androgen-blocking therapies or androgen blockers such as enzalutamide or abiraterone or apalutamide. And these PARP inhibitors such as olaparib or rucaparib can be used for those patients as single agent if they have these DNA repair mutations. Now, last year, we saw several combinations of PARP inhibitors with these androgen or novel hormonal therapy, as we call them. And these include abiraterone plus olaparib, abiraterone plus niraparib, and talazoparib plus enzalutamide from various phase 3 trials. Now, I'd like to bring to your attention that these PARP inhibitor combinations are approved with different indications in the United States and in the European Union. And they continue to get approved in various other countries.

So the combination of abiraterone and a PARP inhibitor, whether it is olaparib or niraparib, they are approved for patients who have new metastatic castrate-resistant prostate cancer, and they have BRCA1 or BRCA2 mutations in the cancer cells or they have germline BRCA1 and BRCA2 mutations. Enzalutamide and talazoparib combination is approved in the United States for patients with metastatic castration-resistant prostate cancer with BRCA1 and BRCA2 mutations, but also several other DNA repair gene mutations. And that's a big difference as far as approval is concerned in the U.S. In the European Union, for our patients who are listening from European Union, the combination of abiraterone and olaparib and enzalutamide and talazoparib are approved for patients with metastatic castrate-resistant prostate cancer where chemotherapy is not clinically indicated, regardless of whether they have mutations in the DNA repair genes or not. And the combination of abiraterone and niraparib is only approved for patients with metastatic castrate-resistant prostate cancer with BRCA1 and BRCA2 mutation. So I just wanted to outline the different indications in the United States and in the Europe.

Dr. Grivas: Thank you so much, Neeraj. So eloquent and very relevant to multiple patients globally, as you pointed out, with some differences in terms of the regulatory approval and availability of those agents in different countries. So great insights. Maybe we'll ask you 1 more question again since we are doing the highlights of the year.

Another very important area of therapeutic development has to do with these novel agents that target the prostate cancer cells, and we call them theragnostics as a broader term. And I will let you explain what that means maybe in lay terms for our audience. And specifically, if you can comment on the recently presented PSMAforetrial at the ESMO meeting in Madrid with lutetium-177 PSMA. What are the implications of these results for our patients, and what is the role of lutetium therapy in this particular therapy setting?

Dr. Agarwal: Of course, very important and pertinent topic indeed. As our patients may know that lutetium-177 therapy, or simply speaking, lutetium therapy, has already been approved for patients with metastatic castrate-resistant prostate cancer who have had disease progression on this novel hormonal therapy and a chemotherapy with docetaxel or cabazitaxel. And this indication is already there in the U.S. and in various other countries. And patients are eligible to receive lutetium therapy as long as their disease has progressed on docetaxel or one of the taxane chemotherapy and a novel hormonal therapy.

Now, in the European Society of Medical Oncology meeting, Dr. Oliver Sartor presented the data on PSMAfore trial where lutetium therapy was used before chemotherapy. In this trial lutetium therapy was compared with another novel hormonal therapy after disease progression on 1 novel hormonal therapy. And there was approximately 6-month improvement in progression-free survival, meaning there was a delay in disease progression by 5 to 6 months in patients who were receiving lutetium therapy. And at the time of the report, there was no improvement in overall survival, with the caveat that 84% patients who were receiving novel hormonal therapy, actually, they switched over to lutetium therapy after disease progression. So, overall, survival data may not be met. Having said that, we already know that lutetium therapy is an effective therapy, and it has a definitive role in treatment of our patients with metastatic castrate-resistant prostate cancer.

Dr. Grivas: Thank you, Neeraj. That's very, very important data. And I'm so glad we have many more therapy options for our patients with prostate cancer. So involvement and accrual in clinical trials, I'm sure you will agree, is a very important and high priority. And I always encourage people with prostate cancer to ask about clinical trials that are relevant to their situation.

Dr. Agarwal: Yeah. I'd just like to add a point regarding lutetium therapy that there was a phase 2 trial in from Australia which compared lutetium therapy with cabazitaxel therapy after disease progression and docetaxel chemotherapy. And efficacy of both agents were not very different. So just wanted to make that point.

Dr. Grivas: Thank you, Neeraj. It's a very important point. And obviously, always want to think about pace and preference, convenience, distance from the cancer centers, all the relevant points, how we can individualize suggestions or recommendations for our patients. Thank you so much, Neeraj, for your wonderful input, insights, and all the work you do in the field.

Dr. Agarwal: Thank you very much for having me.

Dr. Grivas: Of course, of course. And now we're going to transition to a different cancer type. We're going to talk about bladder cancer and urothelial cancer in general, urinary tract cancer. And we're delighted and excited to have Dr. Shilpa Gupta from Cleveland Clinic, who's a professor there of oncology. Shilpa, I want to introduce yourself?

Dr. Gupta: I'm Shilpa Gupta. I'm a genitourinary medical oncologist and the director of the GU Program at Cleveland Clinic. I'm really excited to be doing this podcast with you all.

Dr. Grivas: Thank you, Shilpa. You have done amazing work in the field, pushing the field forward. You are part of those transformative studies. I will ask you in the beginning where I'm going to focus my first question for people who have advanced or metastatic bladder cancer or urinary tract cancer or upper or lower tract. And we saw really exciting, impressive data at the recent ESMO Congress in Madrid a couple of months ago. And I know you were there and were enjoying to see the improvement in patient outcomes that comes with better quality of life for patients in the last several years. And the question I have for you, if you want to summarize the key data in the first-line treatment, patients who have no prior treatment for metastatic urothelial cancer, what are the key data we showed at the ESMO meeting?

Dr. Gupta: Thank you, Petros. As you said, this is a really exciting time for both patients as well as the physicians treating bladder cancer because of all the new developments which we've seen after decades. So at ESMO 2023, we saw the key data from the EV-302 trial, which was a phase 3 trial, which randomized patients to the standard of care, platinum-based chemotherapy, gemcitabine-cisplatin or gemcitabine-carboplatin, versus a novel drug, which is an antibody-drug conjugate called enfortumab vedotin and the immunotherapy pembrolizumab. And the primary endpoint was to see if patients lived longer and this delayed progression. And we saw that in this the progression-free survival, we saw that it was 12.5 months with enfortumab vedotin and pembrolizumab compared to 6.3 months, which means that the risk of progression or death was decreased by 55% with this new combination. And the benefit was seen across all the various factors, especially patients with liver metastases, visceral metastases, whether or not they had contraindications to receiving cisplatin or not or PD-L1 expression. So this is the first time we saw such a remarkable benefit with any treatment that beat platinums. And the overall survival was also doubled: 16 months in chemotherapy versus 31.5 months with this combination. So the risk of death was reduced by 53%. And we also saw that the overall response rates were 68% with this compared to 44% with chemo. And 29% of patients had complete responses. And this was really remarkable because we have not seen such data before.

And in the same session, we also saw another phase 3 trial that was presented, which was the Checkmate 901 trial, in which the investigators tested whether the addition of immunotherapy called nivolumab to the standard of care, gemcitabine and cisplatin was better than gemcitabine and cisplatin alone. So this was a study only looking for patients who can receive cisplatin.

So patients were randomized to 6 cycles of gemcitabine cisplatin versus nivolumab, gemcitabine cisplatin for up to 6 cycles. And after that, they continued nivolumab maintenance every month for up to 2 years. And in this, the primary endpoint of overall survival was also met, although the difference was not as huge as the other study. It was 18.9 months with chemotherapy versus 21.7 months with the combination. And progression-free survival was also improved by just 0.3 months with the combination. And the objective response rates were higher with the combination, 57% versus 43%, and there were 21% complete responses.

So the bottom line is that both these trials showed us that the frontline treatment is not going to be just platinums anymore moving forward. We will have the option of the enfortumab vedotin and pembrolizumab for all comers, patients who can get platinums, and nivolumab and gemcitabine cisplatin for patients who are cisplatin eligible.

Dr. Grivas: Thank you, Shilpa. Wonderful summary. Really, really exciting time to see the field moving forward and translate those results to longer life for our patients. In that context, I will also ask you—I asked Neeraj before about genetic testing in prostate cancer. I will ask you a similar question about genetic testing in bladder cancer. Again, reminding the audience about the distinction between germline testing, which is the DNA we are born with, and somatic testing, which is the cancer-specific genomic changes. Could you comment on the importance of genetic testing in bladder cancer?

Dr. Gupta: Yes. Absolutely, Petros. Genetic testing in urothelial cancer is very important because for the first time a few years ago, we saw a drug targeting the fibroblastic growth factor receptor or FGFR alterations. This drug is called erdafitinib. It is the first targeted therapy to be approved in urothelial cancer. It is only seen in up to 20% of patients who harbor these alterations for whom this option may be viable. And we saw initially that erdafitinib was approved in patients who harbor these alterations in the phase 2 BLC2001 trial where it showed response rates of 40% and encouraging progression-free survival, and overall survival. And then we also saw in a phase 3 trial called the THOR trial where patients who harbored these alterations by genetic testing, erdafitinib was much better than chemotherapy, prolonged survival by almost 4.2 months compared to chemotherapy. So unless we are testing, we won't find this. So it is really important to test all our advanced disease patients so we are not depriving them of this additional targeted therapy.

Dr. Grivas: Thank you, Shilpa. Very important message for our patients to definitely discuss the value of genetic testing. And if we think about therapy implications, specifically genomic changes, DNA changes in these FGFR-2 and FGFR-3 genes are very relevant and important for potential therapy with this agent called erdafitinib. Shilpa, a quick comment. We saw data from THOR cohort 2 comparing erdafitinib with this inhibitor of this FGFR that we just talked about compared to pembrolizumab, which is an immunotherapy drug inhibiting a checkpoint of the immune system. Could you quickly comment on that? And I think both options are available for our patients and sometimes just comes down to the sequence based on a particular patient case.

Dr. Gupta: So Petros, as we had thought that patients who harbor these alterations in their tumors, they may benefit from using targeted therapy before immunotherapy. That was the premise of the cohort 2 of the THOR trial, that patients will do better if they received erdafitinib first after progressing on 1 prior line of therapy, which is not an immunotherapy. So patients were randomized to erdafitinib versus pembrolizumab. Of course, all of them had to have the FGFR alterations. The primary endpoint was overall survival. Initially, like I said, the study assumed that there'll be 46% improvement in overall survival with erdafitinib over pembrolizumab. However, the study was a negative study. There was no difference in the overall survival. And what that means for our patients is that erdafitinib right now is positioned for patients who've had prior platinums and immunotherapies. So erdafitinib should not be used before immunotherapy. So I think this is the first study that really settles the question of sequencing for our patients. And I think the message is that in a patient's journey, they should be getting all these therapies. We just now know that it's better to use pembrolizumab before erdafitinib and not vice versa.

Dr. Grivas: Thanks, Shilpa. And then really, really interesting to see these trials being reported. And as you said, individual discussion with the patients and the response rate may be another factor to consider. If someone wants to have a more rapid control of the cancer of the disease, we may potentially think about an agent with high response rate and vice versa. So I think to your point, individual decisions. And I think patients asking those questions is very important in the clinic to help select the right patient for the right treatment for the right patient.

Dr. Gupta: Yeah. Absolutely, Petros. They did see that the response rates were 40% with the erdafitinib versus 21% with the immunotherapy. So using that information can sometimes guide us if a patient has high disease burden.

Dr. Grivas: Thank you, Shilpa. That was very insightful. And thank you for all you are doing for the patients and the field in general. You really, really have helped the field move forward. So congratulations and thank you. And we're going to transition to another superstar in the field of GU cancers. Very excited to host Dr. Tian Zhang. Dr. Zhang is in UT Southwestern in Dallas. Tian, you want to introduce yourself?

Dr. Zhang: Hi, Petros. Thank you so much. Tian Zhang, I'm a GU medical oncologist and associate professor at UT Southwestern Medical Center in Dallas.

Dr. Grivas: Wonderful. Thanks, Tian. Again, the same comments. All the work you're doing in the field is tremendous. Thanks for joining us today. Tian, we saw some very interesting data at the ESMO meeting. And since we're doing the highlights of the year, I think the predominance of the data we saw at the ESMO meeting was about this drug called belzutifan, where I will ask you to enlighten us what exactly this is. And particularly, we saw 3 different trials. I would probably ask you to focus more on the LITESPARK-005. What was the trial design and what was the primary goal of the study? When patients go on this drug, what they should be aware in terms of side effects? And what was all this discussion that the take-home message at the end of ESMO regarding belzutifan? Thank you.

Dr. Zhang: Sure. We'll parse that one at a time. Belzutifan, I hope many of our audience knows is a small molecule inhibitor of the HIF complex, a hypoxia-inducible factor complex, which is implicated in the development of kidney cancers. And this biology actually contributed to the Nobel Prize in 2019. Understanding the structure of the HIF complex and how to target it. For a long time, HIF was thought to be un-targetable. And so the fact that there were small molecules identified actually here in Dallas at UT Southwestern that inhibits the dimerization of the HIF complex is really novel and shows us the bench-to-bedside translatability of these preclinical discoveries.

And so there were a couple of molecules that were discovered here on campus and they paved the way for what became molecules that have now made it to clinic, in particular belzutifan. And so we've had belzutifan now approved for Von Hippel-Lindau Syndrome over the last 2 years or so. So many of us are familiar with using this drug in the clinic. It's an oral agent that's able to target the HIF complex and block it and really control the spread of clear cell kidney cancers, in particular in Von Hippel-Lindau disease. 

LITESPARK-005, the trial that you're alluding to, there was a registrational trial for belzutifan across other kidney cancer populations. And this trial was the 1 that made, I think, the biggest impact of the 3 trials that were presented at ESMO this year.  LITESPARK-005 was a phase 3 trial of patients who had metastatic or locally advanced clear cell kidney cancer who had progressed after prior systemic therapies, not more than 3 prior lines. And they were randomized to either belzutifan at the 120 milligrams daily dose or everolimus at the 10 milligrams daily dose. And the primary endpoint was delay of progression. So progression-free survival as well as overall survival. So we saw the primary endpoint of these was met for progression-free survival.

There was about a 26% risk reduction for progression for patients treated with belzutifan versus those that were treated with everolimus. The objective response rate I would highlight is also significant for the patients treated with belzutifan. There was actually a 3.5% complete response rate and objective responses. So including partial responders was about 23%.

I would say that patients who are treated with belzutifan need to be aware of the side effects of anemia and also hypoxia [low levels of oxygen in the body]. And in fact, higher grades of anemia can occur in up to a third of patients and higher rates of hypoxia. So low oxygen saturations can occur in up to 10% or so of patients. And so that's really important when we're thinking about those toxicities and how we might hold or support the side effects with growth factors, for example, for the anemia. Otherwise, it's quite well tolerated as a single agent.

As you alluded to, there was 1 controversial aspect of this particular trial because the control cohort was treated with everolimus. And everolimus as a single agent may not be what people use at this point in the refractory setting. But it is an acceptable approved treatment option for patients in the refractory kidney cancer setting, and therefore, it was chosen as the control cohort. And belzutifan did improve compared to a known standard of treatment. So I think that's really important to add to our armamentarium in refractory disease.

Dr. Grivas: Wonderful, Tian. Thank you so much for a really, really comprehensive and detailed review. We'll have to see whether it will be available for patients with advanced clear-cell kidney cancer. To your point, it's already available for patients with this condition that you mentioned, the Von Hippel-Lindau genetic condition. So it's great to see more options available for our patients.

Maybe I'll ask you another quick trial to comment on Tian, and I'll ask you individual questions to make it easier, to your point, for the audience to follow. And I'm referring to the RENOTORCH trial. This was conducted in China, and I think it was practice-changing there. Could you tell us the study design?

Dr. Zhang: RENOTORCH was another phase 3 randomized trial. It was conducted all in China of patients with unresectable metastatic clear cell kidney cancer, no systemic prior therapy, and also intermediate- and poor-risk disease by IMDC criteria. So these were all first-line metastatic disease, and patients were randomized to either toripalimab, which is their PD-1 inhibitor, plus axitinib versus sunitinib. So this is a trial design that mirrors many of our prior trials in the first-line metastatic setting that have led to approvals of VEGF IO [immunotherapy] combinations. But this is the first one that was carried out purely in the Chinese population and important for the Chinese population to gain access to these types of combinations.

Dr. Grivas: Thank you, Tian. Very important to see this global approach, as you mentioned, oncology and see trials from different countries. What were the main findings of this trial?

Dr. Zhang: Sure. The primary endpoint was progression-free survival of the 2 cohorts. And they randomized about 420 patients. About 80% per cohort had intermediate-risk disease. And the combination of axitinib with toripalimab did improve progression-free survival. So it had a 35% risk reduction for progression over time. So it did meet its primary endpoint.

Dr. Grivas: Thank you, Tian. It's great to see progress in the field. As I mentioned, new agents, positive trials. Could you comment a little bit on the side effect profile and the significance of this trial for our patients worldwide?

Dr. Zhang: Sure. When we're talking about VEGF IO combinations very similarly as to the prior trials that we've seen in the toxicity profiles, we're thinking a lot about the immunotherapy toxicities of rashes and colitis [inflammation of the colon], endocrinopathies [hormone problems], as well as the rare inflammatory reactions of the liver, lungs, or kidney, but also added in the small molecule effects of hypertension, hand-foot syndrome, and mucositis [mouth sores] and taste changes. So very important to think through those side effect profiles as our patients are being treated with these combinations.

Dr. Grivas: Thank you so much, Tian. Great to see, again, this progress made worldwide. And I think it speaks to the idea of how we can have equitable healthcare delivery across the globe, right, and have agents accessible in different parts of the world.

Dr. Zhang: Absolutely. In fact, I would just add that the Chinese population haven't actually had access to drugs like cabozantinib. And this is their first phase 3 grade 1 evidence for a combination of VEGF with IO combination. So it's really important that these trials are carried out in the populations where we try to find the effect and see that the consistent benefit is there so that those patients have access to all of these treatment options.

Dr. Grivas: Thank you, Tian. I appreciate your wonderful insights and all your amazing contributions in the field and your research. It's really, really inspiring to see. And I'm going to transition now. Last but not least, we're having the honor of hosting professor, Dr. Tim Gilligan, who is in Cleveland Clinic, and Tim is a world-known expert in urinary cancers, including testicular cancer. Tim, would you like to introduce yourself?

Dr. Gilligan: Yes. Hi. So I think you just did. Tim Gilligan, an oncologist at Cleveland Clinic. I chaired the NCCN panel on testis cancer and edit the UpToDate sections on testis cancer with their help.

Dr. Grivas: Fantastic. Thanks, Tim, for being with us today. And all the work you have done for our patients with GU cancers, testicular cancer, and a lot of work is being done with the NCCN and other guidelines. And you are co-chairing the NCCN guidelines, to your point. Tim, a lot of discussion is happening nowadays across cancer types regarding the role of what we call biomarkers, which are potential features that can help us select patients for the right treatment or help us estimate the prognosis, how long people live. Could you comment a little bit on this biomarker called microRNA in patients with testis cancer? How do you envision this being developed in the future? Is it ready for prime time or not yet?

Dr. Gilligan: And that's an important question. It's not ready for prime time yet, but we are making progress. There are a couple of areas where it could be very useful. So for example, in stage I testicular cancer, we tell patients to go on surveillance because they're usually cured with orchiectomy [surgical removal of the tumor and testicle], but there is a risk of relapse, and that risk of relapse is highly variable. And our current risk stratification systems for predicting who's going to relapse, who has stage 1 disease, are helpful, but they're far from perfect. And so there was data presented this year that mRNA may be more accurate at predicting for men with stage I non-seminomas who's destined to relapse. And so the implication of that would be if you are positive for mRNA, this particular mRNA for non-seminoma and you have stage I disease, normal scans, normal markers, you could identify a high-risk group of patients who maybe should get a cycle of BEP chemotherapy rather than waiting. If you know they're going to relapse, you're going to have to get them 3 cycles of BEP, why not just treat them right away? Or maybe RPLND [retroperitoneal lymph node dissection] could be helpful in that setting. We don't know. But we would need to do studies validating that approach.

There is data showing that it does predict relapse, but it's not at the point of saying, "Are the patients really going to do better with immediate treatment and which treatment is going to be best for them?" But I thought that was an important finding and really an example of how we think we're going to use it, which is to find relapse a lot earlier and so that we can give a less toxic treatment. And the benefit of that is that we know more and more that chemotherapy is toxic and resulted in second cancers. For men who get multiple cycles of cisplatin-based chemotherapy, or if they get radiation therapy, they're at higher risk of dying of other cancers than the general population. So if this could help us find early relapses, treat it more gently, less aggressively, have late, less toxicity, and the same cure rate. That would be great. So we're not there yet, but I think we're going to get there.

Dr. Grivas: Thanks, Tim. Very, very helpful to know. So this microRNA 371 that we talk about is not ready for prime time, but you definitely see promise for the future, and more trials, more studies are being done. Again, illustrating the importance of clinical trials that can help us evaluate the added value of a particular biomarker, including this particular microRNA that we talked about.

Dr. Gilligan: Before you change the subject on getting to crude biomarkers, there was also an interesting abstract showing that for stage I seminoma. If we actually use our current markers, we may be able to predict much more accurately. And it'll be interesting to see if that changes. They looked at the variables of lymphovascular invasion, invasion of the hilum of the testis, whether or not preoperative markers were elevated, LDH, and beta HCG. What was interesting to me about that paper was that this is about 900 patients. It was pretty large. That if you had all 4 risk factors, the relapse rate was about 64%. Whereas your average relapse risk for stage I seminoma is about 15%. We put everyone on surveillance. If we started if that model is persuasive to the community and starts getting used, then maybe patients with those 4 risk markers who most of whom are going to relapse, according to this data, maybe you want to treat those people and not put them on surveillance. So that'll be interesting to follow up on too.

Dr. Grivas: Thanks, Tim. And you are referring to currently available blood tests, right, that can be used, and we use them in clinical practice. So we just put them together, try to get a sense of the chance of cancer coming back, what we call recurrence, and how long people may live. That can help us make a therapy decision. Thank you, Tim. This is very, very interesting. And I'm glad to see the progress in the field.

I think you alluded to that before, but there is a trend discussing when we have a removal of the testicle for a patient with testis cancer, what to do next, depending on the stage, those markers that the blood tests you told us about. What about the role of surgery for removal of lymph nodes, for example? And do you see a trend going forward that in many selective cases, certain scenarios, we may potentially select surgery as opposed to chemotherapy or radiation to avoid these potential complications down the road? And if so, which are those patients who may benefit from surgery?

Dr. Gilligan: Yeah, an important question. I think surgery, there's been a growing interest in using surgery rather than chemotherapy in order to avoid late effects. So retroperitoneal lymph node dissection (RPLND) is the most obvious example of that. There is data now showing that most patients with stage II seminoma can be cured with retroperitoneal lymph node dissection. We used to treat those patients with chemotherapy or radiation, but as I've noted, both of those are associated with an increased risk of second cancers down the line. So there are papers on both sides of the Atlantic showing that you can cure most people. However, it is important to note that the relapse rate after surgery is significantly higher than the relapse rate after chemotherapy or radiation. If you take a stage II patient and treat them with chemotherapy or radiation, you're going to cure well over 90% of them. Whereas the relapse risk with surgery, depending on what you find at surgery, is going to be higher. So on average, it's going to be in the realm of 20%, maybe as high as 30%, depending on which paper you look at. And if you take patients who have PN2 disease, so a lymph node is 2 centimeters or bigger, 25% or more of those patients are relapsing after surgery.

So it's important for patients to understand that this treatment has the benefit of avoiding chemotherapy for most patients, but it also has a higher risk of relapse than the old treatments. We still think it's attractive because if you can avoid chemotherapy in 3 out of 4 patients or 4 out of 5 patients, that's a benefit to those patients. And also, if you go in and find a significant amount of cancer at surgery, you can give 2 cycles of chemotherapy right away and almost eliminate the risk of relapse, which is less chemo than they would be getting upfront, which would be 3 or 4 cycles. So one of the emphasis now is really trying to avoid late toxicities if we can. You sometimes see that even in the metastatic setting in terms of resecting residual masses and situations where we maybe in the past would have thought about second-line chemotherapy. I think people are more thinking about opportunities to use surgery instead to try to limit the quantity of chemo that we're giving. Those are much trickier decisions than the stage II decisions, but definitely a growing interest in surgery rather than chemo.

Dr. Grivas: Thank you so much. It's really, really exciting to see that testis cancer was really transformed in the past with developments of therapies like chemotherapy, radiation therapy, and surgery. And it's great to see this evolving down the road.

And I think all of the above that you mentioned evolves through the conduction of clinical trials. And as I mentioned before, I think it's so important to give the opportunity for patients and families to review clinical trial options. I think it's critical to try to help them, but also help other patients, the community, the society in general. So I always try to underline the importance of clinical trials across the board.

And on that note, I think we had such a successful year, 2023 across GU cancers. It's so great to see the progress being made. All of us are looking forward for more exciting research being done in 2024 and beyond. And on that note, I want to thank so much Dr. Agarwal, Dr. Gupta, Dr. Zhang, and Dr. Gilligan for wonderful insights and all the great work they're doing in the field of GU cancers.

As the editor for the GU Cancers for the wonderful Cancer.Net, I'm so proud of this team and really, really looking forward to further podcasts like this and how we can better serve the educational mission for ASCO, working with the wonderful staff at Cancer.Net. Thank you so much, all of you, for your time today and all you are doing.

Dr. Gupta: Thank you, Petros.

Dr. Zhang: Thank you, Petros.

ASCO: Thank you, Dr. Grivas, Dr. Agarwal, Dr. Gupta, Dr. Zhang, and Dr. Gilligan. You can learn more about new research in genitourinary cancers at www.cancer.net.

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The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this Meaningful Conversations podcast, Dr. Richard Lee talks to Dr. Tara Sanft and Dr. Biren Saraiya about what people with advanced cancer should know, including the value of palliative and supportive care and ways to talk with their families and healthcare teams about their health care wishes.

Meaningful Conversations is a Cancer.Net blog and podcast series that describes the important discussions people may need to have with their providers, caregivers, and loved ones during cancer and offers ways to help navigate these conversations.

Dr. Lee is a Clinical Professor in the Departments of Supportive Care Medicine and Medical Oncology at City of Hope Comprehensive Cancer Center and serves as the Medical Director of the Integrative Medicine Program. He is also the 2023 Cancer.Net Associate Editor for Palliative Care.

Dr. Sanft is a medical oncologist and Chief Patient Experience Officer at Smilow Cancer Hospital, the Medical Director of the Yale Survivorship Clinic, and Associate Professor of Medicine in Medical Oncology at Yale School of Medicine.

Dr. Saraiya is a medical oncologist at Rutgers Cancer Institute and Associate Professor of Medicine in the Division of Medical Oncology, Solid Tumor Section at the Rutgers Robert Wood Johnson Medical School.

Both Dr. Sanft and Dr. Biren are members of the 2023 Cancer.Net Advisory Panel for Palliative and Supportive Care.

View disclosures for Dr. Lee, Dr. Sanft, and Dr. Saraiya at Cancer.Net.

Dr. Lee: Hi, my name is Richard Lee. I'm a clinical professor here at City of Hope and also the Cherng Family Director's Chair for the Center for Integrative Oncology. I'm really happy to be here today and talking about the topic of advanced care planning. And I'll have Dr. Tara Sanft and also Dr. Biren Saraiya introduce themselves as well.

Dr. Sanft: Thanks, Dr. Lee. I'm Tara Sanft. I'm a breast medical oncologist at Yale Cancer Center and Smilow Cancer Hospital in New Haven, Connecticut. I am board certified in medical oncology and hospice and palliative medicine. I do direct the survivorship clinic, which is an appropriate place for advanced care planning that we can touch on today. I'm really happy to be here.

Dr. Saraiya: Hi, my name is Biren Saraiya. I'm a medical oncologist focused on GU medical oncology and also a board-certified palliative care physician. I'm at Rutgers Cancer Institute of New Jersey. My focus is on decision-making. My research interest in decision-making and end-of-life planning for patients with serious medical illnesses. And I do a lot of teaching on this topic at our medical school. And I'm also glad to be here, and I do not have any relevant financial disclosures.

Dr. Lee: Thank you so much for both of you for being here. I should also add, I don't have any relevant financial or disclosures, conflicts of interest.

Dr. Sanft: Thank you. I'd like to add that I do not either. Thanks for the reminder.

Dr. Lee: Yes. Thank you both. And so this is a really important topic that we deal with when we see patients, especially those with more advanced cancer. Could you talk about when we say advanced cancer, what does that really mean?

Dr. Saraiya: When I think of advanced cancer, it is either cancer that has come back, recurred, or that is no longer curable, no longer something that we can't completely get rid of. So many times, it is what we call stage four cancer. Each cancer is a bit different. So it's a general rule of thumb, but not necessarily intelligible for every single cancer. But that's what I mean when I say advanced cancers to my patients.

Dr. Lee: How about yourself, Dr. Sanft? Do you use a similar concept, or is it a little bit different?

Dr. Sanft: I agree with all that's been said. Advanced cancer typically involves the spread of the cancer to other sites outside of the primary site. And the strategy tends to be a chronic long-term management strategy rather than curative treatment, although not always. And as our science becomes more advanced and sophisticated, these terms can apply to people with all different tumor types and locations of involvement, and that's really exciting. But in general, advanced cancer is very serious and can often be life-threatening and needs to be dealt with always.

Dr. Lee: And that leads into the next question, which is, if it's not possible to completely cure the cancer, does that mean there's no treatment available for these patients?

Dr. Sanft: Absolutely not. Does it mean that there is no treatment? Even when anti-cancer treatment may not help the situation, there is treatment. And I think as palliative care professionals, in addition to being medical oncologists, treating symptoms and treating suffering that comes with symptoms from cancer is always on the table from the time of diagnosis through the balance of life. And when a diagnosis comes through that is life-threatening or advanced or stage four, it is very common to pursue anti-cancer treatment, sometimes many different types of treatment. And it's very rare that someone with a new diagnosis of advanced cancer would not qualify for any anti-cancer treatment.

Dr. Lee: Thank you. And moving along with that same concept, Dr. Saraiya, could you talk about what are the kinds of treatment options available to patients with advanced cancer? And then could you comment a little bit what Dr. Sanft was talking about, which is also there's anti-cancer treatments, but then there's also these treatments that help with quality of life and symptoms. And can they be coordinated together? Are we choosing one or the other?

Dr. Saraiya: That's a great question. The way I think about this is I always want to focus on what's important for the person in front of me, what's important for the patient. And so even when there is no cure for the cancer, it is certainly treatable. And as Dr. Sanft pointed out, we have many treatments, many types of treatments. So they are delivered by someone like me or Dr. Sanft who are medical oncologists, but also by our colleagues in radiation and surgery and our colleagues in palliative medicine. So it depends on what the symptoms are; we can discuss how to best address it. And sometimes it requires radiation, short course of radiation. Sometimes that's the most effective thing. Sometimes it requires medicines that are by mouth or chemotherapy that are intravenous or by mouth or immunotherapy or different kinds of newer agents that we are using these days. So they can be delivered under the care of a medical oncologist. We can also have sometimes something that's very painful, and the surgeon can remove it. And that is also just as good of an option.

So what we choose to do depends on what the objective is, what we are trying to accomplish. And to me, at any point in time I see a patient, every single person I meet with, my goal is how do I help them live better? What's important for the quality of life? And many times is what I do as a medical oncologist, many times it's just listening to them and talking to them and providing support, either myself or my staff or social work. And many times, it's my colleagues in palliative medicine who are helping me care for their symptoms such as pain, other symptoms that I may have a hard time addressing by myself. And so we call on their help when we can't address it.

Dr. Lee: We've touched upon the topic of palliative care and supportive care, that terminology. And I'm wondering if you could expand on that so we have a common understanding. And how is that different than hospice care?

Dr. Saraiya: This is how I explain to my patients and my students, which is to say, when I went to medicine and I asked my students this question, how many times do we actually cure cancer or cure anything, forget cancer, just anything? And the fact is that most times we don't cure many diseases. So things like high blood pressure, diabetes, high cholesterol, heart disease, liver disease. We don't cure things outside cancer as well. But what we do is we help patients live long and well for long periods of time. We focus on quality of life. And in essence, we are providing palliative care. So I define palliative care anything that helps patients live better or live well. Sometimes we can cure things as well. So many cancers are curable. But let's say you have extensive surgery for a cure of the cancer, but you have pain from the surgery. We certainly help give you pain medicines. That's palliative care. And so for me, palliative care is anything that we do to help alleviate patient's symptoms. It can be delivered by the surgeon who prescribes pain medicine postop, by radiation doctor, who helps with palliative radiation, by medical oncologists like myself and Dr. Sanft, who give medicines for nausea, vomiting, or other symptoms that either the treatments or the cancer itself is causing.

When we need help of our colleagues who specialize in this is specialized palliative care. And some just call it supportive care. It's just a naming terminology. As long as we are helping patients live better, any intervention we make to me is palliative and supportive care. At a time when we agree, both patients and we agree that look, our focus is just on comfort. We are not going to focus on cancer anymore. And we're going to focus on just quality of life. That can be dealt with palliative care and hospice care. Hospice care is a very specific defined insurance benefit that requires certain certification. And that's the difference. So palliative is something required from day one, I meet a patient. It doesn't matter what they have until the end of their life. And sometimes even after that, caring for their loved ones after the patient has died is also palliation. Hospice care is a very small piece of that when we are just focused on end-of-life care.

Dr. Lee: I appreciate that understanding. And I think it's a great point that you make that anyone can be providing palliative and supportive care. It doesn't take necessarily specialists, but different types of oncologists and other clinicians can be providing in addition to specialists. And Dr. Sanft, could you talk a little bit about this concept about after kind of after a patient may pass through hospice? Dr. Saraiya was mentioning about emotional and spiritual support. How can we help patients find that kind of support from diagnosis through the whole journey?

Dr. Sanft: Yeah. I really think of palliative care as taking care of the whole patient. So not just treating the disease, but really addressing the emotional, spiritual, and other physical aspects that cancer and its treatment can impact on a human being that's undergoing this. And then, of course, the entire family unit. So the importance of addressing all of these aspects has been shown in so many different ways. And getting palliative care involved early can really impact how that individual does with their disease course. But it can also provide the structures around that spiritual and emotional health for the patient and their family from diagnosis throughout. And as Dr. Saraiya mentioned, when the time gets short and the end-of-life time is near, palliative care and hospice care in particular can really provide a lot of that bereavement support or that anticipation of loss. And then, of course, all the grief that comes after the loss.

Dr. Lee: And could you expand a little bit in terms of if patients are starting to feel some emotional spiritual needs, how do they find help? Or what should they be doing in terms of connecting with their clinical team to get that type of support?

Dr. Sanft: I would like to say first that I think part of it is on the medical team ourselves to ask patients. Our culture in general is not one that often openly discusses emotions. So what I teach the medical students is, for every visit, how are you doing with all of this emotionally? And that is a very open-ended question that patients can reflect on and share what they're comfortable sharing with their providers. Now, not all of us who are practicing learned these techniques when we were going through medical school. So your doctor and medical team might not automatically ask about your emotional health.

So it is within a patient's right to say, "I would like to discuss with you how this is impacting me emotionally. Could I share that with you?" And really, I think most healthcare professionals come into this profession to help. And this is a very rewarding conversation to understand how this is impacting you and your family emotionally and then trying to get the support that is needed. Most cancer teams have social workers that are highly trained in assessing and counseling and helping patients get triaged into the help that they need, whether it be a support group or a psychologist or a psychiatrist or all of the above. Usually, social workers are embedded in many cancer teams. And if it's not a social worker, it may be another trained professional who can deal with this. But certainly, the medical team is the place to start and to really raise emotional health and spiritual health issues, even though we might not routinely be asking at every visit.

Dr. Lee: Great points. And as we think about the journey and we talked a little bit about hospice care and kind of the end phases, sometimes patients fear losing their capacity or ability to really think clearly and maybe even make their own decisions. How can patients in these situations who are concerned about making their wishes known, how can they make sure that's communicated if there is a situation, maybe temporary, maybe longer lasting, which they have trouble with making medical decisions on their own? Dr. Saraiya?

Dr. Saraiya: So I think, hopefully, all adults, all of us, have sort of thought about what-if scenarios in our lives, right? I think the thing I tell my patients that maybe there are three or four people in the room, and it's entirely possible, I'm not the one here tomorrow morning because accidents happen. And we certainly have seen that in our daily lives that suddenly things happen. So hopefully, every adult has thought about it. I always prompt my patients to tell me what they have thoughts about, what thoughts they have had. And I ensure that they have some sort of documentation. This is what we call advanced care planning documentation. Sometimes it's a living will, healthcare proxy. Different states might have different documentation. And many of them may have had it as part of their normal will or their sort of lawyers have drawn it up. I always ask them to sort of just tell me or discuss with me what they have written down. If they have not, I encourage them to have that conversation with their loved one. And there are two points. One, at least have had that thought, and the second, have the conversation.

At no point in time do I want my patients' family, their loved ones, whether it's a spouse, whether it's a child, to have to answer the question, "What do you want for your loved one?" It's always about, "What will your loved one want for themselves?" And so that is my responsibility to facilitate the conversation to make sure that the patient and the family has had that discussion. Once they've had it, document it, whether it's an advanced care planning or many states like my state of New Jersey have specific forms for-- it's called Physician Orders For Life-Sustaining Therapies [POLST]. So especially in a setting with advanced care and we know we had the conversation. We can't cure this. It's about their quality of life, how they want to live. And patients have the absolute right to tell us and guide our decisions in what kind of treatments are acceptable and not acceptable. And that can only happen if you had the conversation. We have discussed things that are important for them. Are they okay being in a situation where they are not able to communicate? And whatever the what-if scenarios are for themselves, let's help figure those things out and make sure that we value their opinion, their autonomy at every single point by completing this advanced care planning documentation, and more importantly, having the conversation with loved ones so they can ask the question, what would your loved one want in the situation?

Dr. Lee: Those are really good points. And I imagine a lot of individuals, a lot of patients, may not have had that conversation. And so what suggestions do you have for patients who are maybe newly diagnosed? They're just totally surprised by the diagnosis. Unfortunately, it may be, in some cases, it's advanced. Dr. Sanft, how would you suggest patients discuss this topic with their family and friends? Are there certain types of questions to be thinking about or certain topics?

Dr. Sanft: Oftentimes, in the midst of a new diagnosis, the whirlwind of having that upside-down feeling is so strong that it's very difficult to then think out into the future. However, once the treatment plan is in place, that tends to be a time where things could sort of be evaluated and the horizon might seem a little bit more stable. And I think most patients are willing to admit that the gravity and the seriousness of the situation that's facing them, yet it's very difficult to really reflect on what might happen in the future or what you might want. I think it's really important from a patient perspective to think, "What are your most important priorities?" And that could be a good framework to start to think about if you aren't able to do these priorities, then what else would you want?

So if being able to walk around your yard and enjoy the garden is a very high priority, even identifying that and understanding that can give you some framework, or talking about that with your loved one can give you some framework down the line if that becomes an impossibility. If interacting and talking with your children or your grandchildren is one of the highest priorities, if that ever became impaired, then how would that influence what you would want? So again, it doesn't have to be yes/no questions that you're answering, but it can really be an understanding of what brings you joy, what are the most important parts of your life, and if those were threatened, then how would you reevaluate the quality of your life?

Dr. Lee: I think that's a good way of framing the priorities and thinking through that with your loved ones. And for Dr. Saraiya, next after they've had some of these discussions, what should they be asking you and Dr. Sanft as the healthcare providers and helping to guide along these important conversations around advanced care planning?

Dr. Saraiya: I will answer that question, but I just want to sort of highlight what Dr. Sanft said is so important, which is really prioritizing and framing. And I think framing is so important. And to sort of put some of the other things Dr. Sanft talked about, the emotional and spiritual support, when someone walks into our office, many times they're really scared. And I take this opportunity to really sort of ask them important questions like, "What are your worries?" Which allows for them to emote a bit about what their worries are. And sometimes it's uncomfortable, right, because they're crying. They're worried about death and dying and what it means for the family. It's hard for the family. It makes a lot of us uncomfortable. But I think it's also very important. So I do take the opportunity early in my interaction with patients just to allow them to emote and just to process their worries. And sometimes I'm acknowledging their worries. Sometimes I'm telling them that those worries are maybe not reasonable, right? Sometimes people say, "Well, I'm going to die next month." And they know that's not the expectation. So they have worries that may be unreasonable.

So I can help talk and address specific worries at that point in time. So we do have to-- and again, this is why we have a team. Many times, patients are not comfortable talking to me about some of their worries, but they are much more apt to talk to my social worker or my nurse or my infusion nurse where they spend hours at times. And they will tell them things that they may not tell me. They will talk about some of the side effects that they have that they won't tell me because they worry. This is my hypothesis and what the research shows. They worry that because I hold that key to that chemotherapy or that key to that treatment, that if this is something that I may not like, I might hold it. And so patients have this natural tendency to not tell me absolutely everything. That's why we have a team. We gather all the information to make sure that we sort of make the right decisions. Sometimes we do have to help patients and families facilitate their conversations to make sure that we address their worries, their fears, their emotions. And it can be done, as I said before, just by us as the primary oncology team or our palliative care team or our social workers or nurses. All of us provide a different role for each patient. And in some patient cases, it is me, and some patients sometimes it's my nurse or sometimes it's my infusion nurse, or sometimes my social worker. And sometimes I do need the help of my palliative care and hospice colleagues.

Dr. Lee: And, Dr. Saraiya, coming back in terms of just guiding patients, are there certain questions you wish your patients might ask you in terms of helping to kind of navigate these difficult conversations?

Dr. Saraiya: I think many patients have this one question, that they have a hard time asking, which is, what's the treatment goal? And many times, we talk about is this something that's treatable. And the answer is yes. That was one of the first questions we're asked. Is it treatable? But many times patients have a question is it curable? And if the answer is no, then what does that mean? Or even if the answer is yes. What does that mean? I think most of us in our lives think about what-if scenarios, but it's really hard to ask those questions. So what I advise and sometimes I facilitate this, but I encourage if you're listening to this, you're a patient, ask your oncologist, "Well, what does this actually mean for me?" And if you have those questions, ask them, "What if this happens? This is my worry. Can I just tell you what my worries are and address them?" And with the worries, also come my hopes. Here's what I'm hoping for. How can I get there? How can you help me get there? And as Dr. Sanft sort of talked about before, if I have a situation where someone tells me, "This is my hope", but I can't do it, it's not likely, I will tell them. But I will also tell them what we can accomplish, what we can do. And so I think having that honest conversation and patients and families can talk amongst themselves, but also with us as clinical teams to just make sure that we, at all points in time, address and put them and their needs in the center of focus.

Dr. Lee: Great questions. And Dr. Sanft, do you have any other questions you wish your patients would ask you in terms of helping to guide these challenging conversations?

Dr. Sanft: It's helpful for patients to come at questions about what to expect directly with us. I think it's most helpful when patients say, "Here's the deal. I'm feeling fine right now, and I want to keep going as long as I feel fine. And I want you to offer me every line of treatment until I don't feel like it's going to be worth it anymore. And we can continue to talk about that. And we'll do this together. I will let you know when I'm ready." And that allows me to say, "Okay. I appreciate what you're saying, and I agree with this plan, and we're on the same page. And when I see signs that things aren't going well, I will tell you." And it sort of sets these expectations upfront that we are all on the same page. We all want the same things. And we commit to each other, "You're going to tell me when this gets too hard, and I'm going to tell you when I think that this isn't helping anymore." And so it allows for this open dialogue to continue throughout.

Dr. Lee: Well, this has been a great conversation, and learned a lot and think about priorities. And I think you make a very good point. This is an ongoing discussion. It's not a single discussion you have, and then it's done. It's really an ongoing process through the whole journey. Do either of you have anything else to add in terms of helping patients who are addressing advanced care planning?

Dr. Saraiya: My biggest ask or sort of consideration is all of us, as Dr. Sanft said in the beginning, all of us came into this to really sort of help. And that is still our primary goal. And good communication really facilitates that. And we have, as a medical team, have to sort of do, as Dr. Sanft pointed out, sort of explore a bit more and really address the concerns. At the same time, you also have to develop a language that we can all understand, both understand, patients and doctors. And I think that's the key work. And I think it's so important to have that partnership with our patients and our families to make sure that we are doing the attentive care that they deserve and they need. So I think having an honest conversation.

One thing I always reflect on is for my patients, they may start in the beginning saying what's most important for me is-- and we are in Jersey so going to the casino on the weekends in Atlantic City. And that's the most important thing for me. But there comes a time when they say, "No, I've changed my mind. Most important thing is having the Friday night dinner with my family." And a few months later, maybe, "I've changed my mind. You know what's really important? If I can just sit in the patio on my rocking chair and enjoy that. Can you help me make those things happen?" I think having those conversations, being aware that we can change our minds, I think is absolutely fine. It's encouraged. And I think that's what we expect.

Dr. Lee: Dr. Sanft?

Dr. Sanft: Oh, I love that. I think I love that. I'm so glad that you brought that up. And the only thing I would add to that is if there are things that you know in your heart you absolutely would not want, telling it to someone, your partner, your family, your decision-makers, and your medical team will really help make sure that that does not come to fruition. So it can be scary to voice those things, but most of us have an idea of what we would never want to have happen. And saying that out loud and making sure that someone close to you, ideally, also your medical team, but certainly someone who's close to you understands what that line is. That can help decisions that need to be made in difficult times make sure that they honor, that they know that that was not what you ever wanted to have, and we can help make sure that that doesn't happen.

Dr. Lee: Well, I want to thank both Dr. Saraiya and Dr. Sanft. This has been fantastic. I learned a lot myself in terms of communication and addressing advanced care planning. And I hope all of you listening also were able to learn some pearls of wisdom from both of them. I think your patients are very lucky to have both of you.

Feel free to look at Cancer.Net if there's more questions and a lot of information around advanced cancer and treatments and advanced care planning and having these discussions. So thank you both again. And stay tuned for more podcasts on these important topics.

ASCO: Thank you, Dr. Lee, Dr. Sanft, and Dr. Saraiya. Find more podcasts and blog posts in the Meaningful Conversations series at www.cancer.net/meaningfulconversations.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

ASCO's first clinical trial is the Targeted Agent and Profiling Utilization Registry, or TAPUR Study. This clinical trial is intended for people with advanced cancer without other treatment options available, and whose cancer has at least one genomic variation that can be targeted with specific drugs.

In this podcast, Dr. Richard Schilsky discusses the TAPUR study and explains why it is significant. He also discusses what participants can expect. Dr. Schilsky is the Principal Investigator for the TAPUR study. He is also the former Chief Medical Officer for ASCO and Professor Emeritus at University of Chicago.

View Dr. Schilsky's disclosures at Cancer.Net.

Dr. Schilsky: Hi, everyone. My name is Richard Schilsky and I'm the principal investigator of the ASCO TAPUR Study and the former Chief Medical Officer of ASCO. I'm happy to give you an overview and update about the study today. By the way, TAPUR is an acronym that stands for Targeted Agent and Profiling Utilization Registry. Hopefully, the reason for naming it that will become clear as you listen. The TAPUR study was conceived in 2013 and launched in 2016, and was based on the observation that there was a rapid increase in testing the tumors of patients with advanced cancer for gene mutations that might be contributing to the growth of the tumor, so-called genomic profiling, in the hope of finding a genomic alteration that could potentially be treated by a drug that was already FDA-approved for a different tumor type than what the patient had.

Meaning, in order for the patient to receive the drug, it would have to be prescribed off-label. The challenge with prescribing the off-label use of a drug is that most insurance plans don't cover the cost of treatment. Additionally, even if the patient were able to receive the drug, there was no mechanism for the oncology community to learn from the patient's treatment experience.

The TAPUR study has managed to address these challenges by providing access to FDA-approved drugs at no cost to the patient and providing treatment results to the oncology community regarding the effects of off-label use of the treatments being studied. Now, TAPUR is a clinical trial, and its primary objective is to describe the anti-tumor activity and toxicity of commercially available targeted anti-cancer drugs prescribed for treatment of patients whose tumors have a genomic alteration known to be a drug target or to predict sensitivity to a drug.

TAPUR was designed to be simple for providers and patients. It's a phase 2 study, meaning that we're aiming to learn about efficacy and safety. It's prospective, that is, it enrolls patients going forward. It is not randomized. Everybody gets a treatment based on the genomic profile of their tumor and the available treatments in the study. It's a multi-basket study. That is to say, multiple therapies are available on the study that are targeting multiple genomic alterations. And it's a pragmatic study. TAPUR attempts to replicate routine clinical care. It's exempt from FDA oversight. It provides oral drugs that can be shipped directly to the patient's home after the first visit.

Now, as I said, the TAPUR study was launched in March of 2016. And as of this month, it's still going strong, with more than 2,700 patients having been enrolled at 267 locations in 28 states. So how does the study work? Well, a patient's physician has results of a genomic profile of the patient's tumor and determines that a study drug might benefit the patient. The patient then decides to participate in TAPUR and gives their informed consent. A molecular tumor board, which is a group of experts convened by ASCO, is available to consult regarding the proposed treatment or to provide alternative treatment options for the patient. A participating pharmaceutical company, and there are 10 right now, provides the study treatments at no cost to the patient.

The patient is cared for by their own oncologist, receives a standard dose of the drug, and is evaluated at standard intervals to see if the treatment is working and if they're having any side effects. ASCO has convened an independent data and safety monitoring board of cancer experts that periodically reviews results and determines whether treatment is promising for a particular cancer type and genomic alteration. That's what we call a cohort in the study. Once the data are finalized, ASCO publishes the study findings in peer-reviewed journals to inform clinical practice and future research.

So let me give you an example. There are specific molecular alterations that often appear in tumor cells that are important for driving the growth and progression of the cancer and can be targeted with specific drugs that interrupt those abnormal molecular pathways. Many of these alterations occur at low frequency, meaning in less than 5% of tumors of any given type. The benefit of the TAPUR trial having a basket design is our ability to evaluate multiple therapies simultaneously to target multiple low-frequency alterations, which ultimately offers more treatment options to patients who wish to participate in the study.

If the TAPUR study were set up looking to target only a single genomic alteration, we would potentially have to screen hundreds of patients in order to find one who is appropriate for the trial, which also means hundreds more would still be left without treatment options. But because TAPUR evaluates multiple treatments and multiple genomic alterations simultaneously, we found that about two-thirds of patients who were screened for the trial ultimately enroll.

A specific example of a drug and targeted gene alteration on TAPUR is the use of the treatment combination pertuzumab plus trastuzumab in tumors with ErbB2 amplification or mutation. Now, you may be aware that ErbB2 is a gene that is synonymous with the HER2 gene that is frequently amplified or overexpressed in patients with breast cancer. And this drug combination, pertuzumab and trastuzumab, is FDA-approved for treatment of patients with breast cancer. But in the TAPUR study, we found multiple tumor types outside the FDA-approved label that can benefit from this treatment if an ErbB2 alteration is detected, including patients with colorectal cancer, endometrial [uterine] cancer, biliary tract cancer, and lung cancer.

To learn more about TAPUR, please follow our progress at the ASCO website. In an effort to provide up-to-date information about cohorts that are available for enrollment on the TAPUR study, ASCO launched a public-facing status report in March of 2023. So first click on www.tapur.org. Click on the link to the ASCO website. From there, select study participation at the bottom of the page. Once at the study participation page, click on the link to see a list of study cohorts that are currently enrolling. The report updates daily, providing viewers with an up-to-date list of available study cohorts based on their genomic alterations. It's important to note that study cohorts are available on a first-to-enroll basis. You can also find information about current results from the TAPUR study on the study results page.

So what have we learned so far? Thus far, we've publicly reported results on 29 cohorts of patients. 17 gave a positive signal of treatment activity, 12 were negative. Now we feel it's just as important to report on the negative results as the positive results. If the treatment is unlikely to be effective for patients, it's important to inform the oncology community because all of the drugs in the study are commercially available and could be prescribed to a patient.

Enrollment to patients on TAPUR is very representative of the U.S. population. The study has broad eligibility criteria that allows more patients to enroll, including patients with an ECOG performance status of 0 to 2 and younger patients. Some treatments allow for adolescent patients as young as age 12 to be enrolled in the study.

We hope the oncology community finds value in the TAPUR study. Physicians have the opportunity to contribute to research and participate in publications and to contribute more knowledge in the field of oncology. TAPUR provides guidance on interpreting genomic reports via the molecular tumor board and provides additional treatment options for patients. Institutions obtain insights on potential new uses of existing drugs and their side effects, and TAPUR data can inform updates to clinical practice guidelines. And patients receive access to drugs not available as standard of care. Patients may be able to receive oral drugs at their home and limit their commute to clinic.

And of course, participation in the study provides an opportunity for patients themselves to contribute to knowledge about cancer treatments. To find a clinical site offering the TAPUR study, please visit the TAPUR website again, www.tapur.org and select "Participating Centers." This will lead to a searchable map of participating sites and includes the site-specific contacts. Contact the primary contact listed for that site. Thank you for listening to this update on the ASCO TAPUR study and enjoy the rest of your day.

ASCO: Thank you, Dr. Schilsky. Learn more about clinical trials, including the TAPUR Study, at www.cancer.net/clinicaltrials.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor for Lung Cancer, Dr. Charu Aggarwal, and Cancer.Net Specialty Editor for Thymoma, Dr. Ryan Gentzler, discuss what people with early-stage non-small cell lung cancer should know about their treatment options before and after surgery, called neoadjuvant therapy and adjuvant therapy, respectively.

Dr. Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine. Dr. Gentzler is a thoracic medical oncologist and Associate Professor of Medicine in the Division of Hematology/Oncology at the University of Virginia (UVA) Comprehensive Cancer Center.

View disclosures for Dr. Aggarwal and Dr. Gentzler at Cancer.Net. 

To begin, Dr. Gentzler will discuss what people with early-stage non-small cell lung cancer should know about neoadjuvant treatment options before lung surgery. Welcome, Dr. Gentzler.

Dr. Gentzler: Hi, this is Ryan Gentzler from the University of Virginia. We're here to discuss the role of neoadjuvant chemotherapy and immunotherapy for the treatment of locally advanced non-small cell lung cancer. So first, I thought I'd address some of the data and definition of what is neoadjuvant treatment. So when we think about treating lung cancer that is not metastatic, that is earlier stage disease, there typically involves multimodality treatment. Sometimes these lesions or tumors can be very small and can be stage I and treated with surgery alone or perhaps radiation alone and no further treatment is needed. But the vast majority of lung cancers that are considered early stage are in fact either larger tumors, involve lymph nodes, and typically fall into the category of stage II or III lung cancers. And these are cancers that often require multiple treatments beyond the local surgery approach alone.

When we think about how we deliver that treatment, it can either be given before surgery or after a surgery. If we give treatment before a surgery, we call that neoadjuvant. If it is given after the surgery, we call that adjuvant. And most of the data that we have today in lung cancer uses one or the other of these approaches, and we don't typically give treatments both before and after, at least in terms of the chemotherapy part of that treatment.

Historically, most of the data exists in the adjuvant treatment of lung cancer going back several decades that showed that the benefit of chemotherapy after a surgery, particularly for those with stage II and stage III lung cancer, derived a clear benefit of survival by giving chemotherapy after surgery. More recently, with the advent of immune therapy, which we have used in patients with stage IV lung cancer as well as those with stage III lung cancer who cannot undergo surgery, those immunotherapy drugs have been shown to improve overall survival and improve clinical outcomes for a wide range of patients with more advanced disease. And so in the last 4 or 5 years, we have really looked at new trials that have added immunotherapy in what we call perioperative space, either before surgery or after surgery for those that have surgically resectable disease.

I'm going to focus on the neoadjuvant approaches that we have seen today, and this largely all started with data from Patrick Forde out of Johns Hopkins and Jamie Chaft from Memorial Sloan Kettering looking at single agent treatment with nivolumab immunotherapy. This was no chemotherapy given for 3 treatments prior to or three cycles prior to surgery. And that trial demonstrated a high degree of patients with tumor reduction and more importantly, we saw that the pathologic response, meaning how much tumor was left under the microscope at the time of surgery, was higher than what anyone anticipated with just immunotherapy alone. That launched a whole series of larger randomized prospective trials evaluating largely the combination of chemotherapy and immune therapy prior to surgery.

Now, before we get into some of the results of these trials, I really wanted to emphasize some of the theoretical advantages to neoadjuvant approach. Now, the first potential advantage of giving neoadjuvant treatment is that we know when you start with immunotherapy and chemotherapy regimens and that's the first type of treatment, everyone is guaranteed to get that treatment. And we know that the completion rate prior to surgery is higher than it is after surgery. These patients can get all of the prescribed treatment and will be more likely to get it than if they get it after surgery. So this is one advantage. The other is potentially starting these medications which go throughout the body and treat the cancer, wherever it may be, earlier. We know that one of the risks of all cancers, but lung cancer in particular, is that even with good surgery and removing all of that cancer, there is a chance that there are cancer cells left behind, which leads to risk of recurrence in the years to come after surgery. Naturally, if we start the treatment that can eliminate those cancer cells, wherever they may be, and do that first, perhaps we catch this earlier with fewer cells that have escaped and have a more likely chance of success of eliminating the cancer and resulting in a cure.

The third, I think, is one that we still have yet to learn more about, but if we give immunotherapy in particular, these are medications that activate the immune system, particularly the type of immune system cell called a T cell. If that T cell is able to recognize tumor cells, it is more likely to be able to continue to attack those tumor cells. And if we give that treatment prior to removal of the tumor, perhaps that activates the immune system in a more robust way that it can go after these cancer cells and eliminate those that are left behind after the surgery. If you give the immunotherapy after a surgery and the bulk of the tumor, most of the cancer cells have been removed, it may be harder to find those antigens or foreign proteins that are expressed in cancer cells. So the immune system may not be as robustly able to go after cancer if you give it solely after a surgery.

Another potential advantage of neoadjuvant approaches is that it really helps us learn as oncologists how well a cancer is responding to a treatment. If we give these treatments for 4 cycles after a surgery, we don't know whether it's eliminating those residual cancer cells or whether it is totally ineffective. If we give it before a surgery and we see that there is tumor reduction or that there is a complete elimination of the cancer, we know that that treatment was an effective treatment at attacking the cancer cells and eliminating them. We know that the cancer was sensitive to that treatment. We can then better prognosticate how well the patients are going to do after surgery. We know based on the latest data that if you achieve what we call a pathologic complete response with chemotherapy and immunotherapy prior to surgery, meaning there are no cancer cells left when we look at that surgical specimen under the microscope, we know that those patients have a much better likelihood of surviving for longer periods of time than those who have active cancer at the time of surgery after prior treatment. And so neoadjuvant approaches allow us in a 2-month time frame to get a great sense of how well our treatments are working and able to prognosticate outcomes based on how well those cancer cells have been eliminated at the time of surgery.

One large phase 3 trial called the CheckMate 816 trial was a randomized phase 3 trial and that enrolled patients with stage IB through IIIA non-small cell lung cancer using the old staging system of the 7th edition. These would all now be categorized as stage II and stage III non-small cell lung cancer patients. And it randomized these patients to 3 cycles of chemotherapy plus nivolumab, which is an immunotherapy drug, and compared that to patients treated with chemotherapy alone for 3 cycles. After these 3 cycles of chemotherapy, which is about a 9-week time frame, patients had surgical resection of their tumors. And then after surgery, patients received no further treatment, although treating physicians were allowed to give additional treatments like chemotherapy or radiation if they thought it would be beneficial for these patients, although it was not mandated by the study. One of the first results we saw from this study was that there was a much higher rate of pathologic complete response of 24% of patients achieving a path CR [pathologic complete response] with the nivolumab plus chemotherapy combination compared to only 2.2% with chemotherapy alone. This was highly statistically significant and demonstrated a clear benefit for those receiving the immunotherapy. The other main endpoint of this study was event-free survival, meaning that the time that the patients were alive and without any significant event like cancer progression or death after the enrollment of the trial. And in this analysis, the median event-free survival was significantly longer in those who have received the immunotherapy plus chemotherapy combination prior to surgery.

One of the potential concerns about neoadjuvant treatment is that it may render patients unfit for surgery who otherwise could have had their cancer removed. When we look at the outcomes from this CheckMate 816 trial, it actually did not appear to be the case to a large degree. In fact, those that got the nivolumab plus chemotherapy combination were more likely to proceed on with surgery, and the majority did; 83% received the planned surgery. There were patients who were unable to receive surgery due to adverse events of their treatment, but that was only 1% of patients enrolled in the trial. Other reasons for canceling the surgery included disease progression, meaning the cancer got worse to the point where they could not undergo surgery, or other reasons, such as the patient declined surgery, or it was found to be unresectable at the time the surgeon wanted to remove the cancer, or poor lung function.

One of the insights we got from the surgical data from this trial were that those who received the combination of chemotherapy and immunotherapy had slightly higher rates of smaller surgeries like a lobectomy compared to a pneumonectomy for those who had received [chemotherapy alone.] There were also fewer numbers of patients who required a conversion from a minimally invasive surgical procedure to an open surgical procedure if they were getting the immunotherapy combination. A higher number of patients also were able to have complete resection of their tumor if they received the immunotherapy/chemotherapy combination. The length of hospitalization was slightly lower, and the rates of pain were slightly lower in those who received the combination as well. These comparisons were not statistically significantly different, but numerically, there seems to be at least a trend toward benefit in surgical outcomes in this neoadjuvant chemotherapy/immunotherapy approach. And I think this makes sense. We know that this combination is more able to eliminate a cancer and make it a pathologic complete response when we look at it under the microscope, and therefore, if there is shrinking the tumor to a higher degree, naturally, it seems there would be more likely of completely removing the tumor, using a smaller incision to remove that tumor, shortening the length of stay in the hospital and recovery time and pain control. All makes sense if we know that the treatment itself is able to reduce that size of the tumor.

There are many other phase 3 trials ongoing studying the impact of immunotherapy plus chemotherapy in the neoadjuvant setting. The AEGEAN trial has recently reported data at the AACR meeting this year in 2023 with similar results that we saw with the CheckMate 816 trial. There are 3 other phase 3 trials that are ongoing, one of which we will see later this summer called the KEYNOTE-671 trial evaluating pembrolizumab plus chemotherapy in the neoadjuvant setting and then 2 other trials evaluating nivolumab, the CheckMate 77T trial, or atezolizumab in the IMpower030 trial.

Each of these more recent trials typically have used 4 cycles of chemotherapy plus immunotherapy prior to surgery and also continued the immunotherapy after surgery for a period of time, most commonly approximately 1 year. From the data we have seen so far, it remains uncertain whether additional immunotherapy beyond the 3 or 4 cycles given in the neoadjuvant setting provides any additional benefit. We still do not understand what to do with patients who did not achieve a pathologic response whether further treatment would be of any additional benefit. We do not know if there will be further benefit even in those that achieved a pathologic complete response whether a slightly longer duration of immunotherapy would further improve outcomes in that group. We suspect with longer-term follow-up over the years of all of these phase 3 trials that some of these questions will be answered.

So what are some key questions that patients should ask when considering a neoadjuvant chemotherapy/immunotherapy approach? I think the first question that's key is what is my tumor stage? We know that the trials that enrolled patients with a neoadjuvant approach enrolled patients using our current staging system would be a stage II or stage III lung cancer. And this is where it gets really tricky is, what subdivision of stage III is it? We tend to think of stage IIIA's as being one that it would be surgically resectable, with a smaller number of stage IIIBs, and then stage IIIC, one that we would not typically recommend surgery for. I think the next question within the tumor stage is, is this based on imaging or based on the biopsies? And we know that biopsies are really the best way to stage locally advanced cancers, particularly getting samples of lymph nodes in the mediastinum. Sometimes what looks like a stage I or stage II on imaging is, in fact, a stage III based on biopsies that are done at the time of surgery. It's ideal to know that information prior to making the decision about surgery so that that surgery is not futile.

On the opposite side, sometimes there is imaging suggestive of lymph nodes that are enlarged in the mediastinum, and it's presumed that this is a more advanced stage III and is not surgically resectable. However, if you go and biopsy those lymph nodes, sometimes they are benign. Sometimes they are inflammation related to infection or cancer but do not actually contain cancer cells. And so we typically advise that getting biopsies of lymph nodes in the mediastinum, at least any that are particularly suspicious, is highly recommended for these locally advanced cancers.

I think the next question that's key to ask is, what are my tumor biomarkers? And there are multiple biomarkers that we look at in non-small cell lung cancer that help us decide what is the best treatment. What is the best approach? What is the best medicine to treat the cancer? We know that one of these biomarkers that is a key is a mutation. So multiple different mutations can occur in lung cancers, particularly those that are adenocarcinoma subtypes. And these mutations may be less likely to benefit from immunotherapy and we may want to take a different approach with surgery, chemotherapy, and potentially targeted therapies that specifically target that mutation that exists in the tumor.

The other key biomarker here is PD-L1. We know that tumors with a higher level of PD-L1 are more likely to respond and benefit from immunotherapy. As of right now, that PD-L1 status plays a more important role in the adjuvant setting. All of the chemotherapy plus immunotherapy combinations in the neoadjuvant setting seem to benefit the group as a whole regardless of that PD-L1 status. But still, an important biomarker that we should have prior to making all final decisions on treatment. I think another question that should be asked any time you have an earlier stage cancer is, is my tumor surgically resectable? And there can be many reasons why cancers are not resectable, perhaps due to the anatomy of where the tumor is located, if it invades into the mediastinum, for example, or is near large blood vessels, or perhaps because there are too many lymph nodes and this is a more advanced stage.

And so I think the main reasons for not being surgically resectable would be the tumor is too large, if the stage is too high, or is it more of a function of fitness for surgery and that can be because of other underlying lung disease. Perhaps removing part or all of a lung would not be safe due to impaired lung function to begin with. And I think it's important to understand that sometimes stage III lung cancers are resectable and sometimes they are not, and understanding the reason why they are not, I think, is important. And then I think lastly and ultimately when we're talking about a neoadjuvant approach, you want to ask your treating oncologist, "Would it be better to give my treatment before surgery or after surgery?" And really discuss the pros and cons with the physician and have them incorporate all of the factors that go into these treatment decisions. How well you'll tolerate chemotherapy, other medical conditions that may play a role in the likeliness of getting through those treatments safely, perhaps underlying diseases that may increase the risk of immune-related side effects with immunotherapy. You really want to factor in all of these things and discuss the pros and cons of a systemic treatment first versus surgery first before making final decisions on how to treat locally advanced lung cancer. All right. Thank you.

ASCO: Thank you, Dr. Gentzler. Next, Dr. Aggarwal will discuss what people with early-stage non-small cell lung cancer should know about their adjuvant treatment options for after lung surgery.

Dr. Aggarwal: This is Dr. Charu Aggarwal. I'm the Leslye Heisler Associate Professor for Lung Cancer Excellence at University of Pennsylvania's Abramson Cancer Center. And today I will talk to you about the use of adjuvant immunotherapy in the setting of early-stage non-small cell lung cancer. We'll start by discussing what adjuvant therapy is, what types of options we have for adjuvant therapy, what kind of testing is important, and what options there may be in terms of adjuvant immunotherapy. So let's get started. Early-stage lung cancer comprises of stages between stage I to stage III. These stages vary by the size of the tumor as well as the level of lymph node involvement.

In the setting of very early-stage lung cancer, such as stage I and stage II, as well as some select stage III lung cancers, we recommend surgical resection. And in these patients, the use of additional treatment is recommended based upon the pathological determination of the tumor size as well as the lymph node status. If usually lymph nodes are involved, we recommend adjuvant chemotherapy, and also, many experts will deliver adjuvant chemotherapy for tumors that may be larger than 4 centimeters even in the absence of lymph node involvement. The data for adjuvant chemotherapy comes from several large clinical trials that were conducted about a couple of decades ago now that demonstrated not only an improvement in preventing recurrence of the cancer but also a modest improvement in overall survival, really laying the ground for improvement and therefore becoming the gold standard. Four cycles of chemotherapy are usually administered about 6 to 12 weeks following surgical resection, and this is really the basis of our treatment in the early-stage setting.

In today's time and age, we now have several other options. We have treatment options that include molecular therapy, which is biomarker driven, as well as the use of immunotherapy. So it's actually very important for us in the adjuvant setting--or in the post-surgical setting--to test for mutations such as EGFR. It's also important for us to test PD-L1 status. So let's dive into why each of these may be important. Patients with EGFR mutations, especially those with sensitizing mutations in EGFR exon 19 or 21, now have the opportunity to receive a targeted therapy in the form of osimertinib, which is an oral drug, very targeted and specific for the EGFR mutation that has been studied in a clinical trial setting in patients with early-stage non-small cell lung cancer. In patients with stage IB to IIIA non-small cell lung cancer with EGFR mutation, use of osimertinib was associated with a significant improvement in our ability to delay the recurrence of cancer. Based on this significant improvement, FDA approved therapy with osimertinib, and it is currently available and ready to use. We usually recommend it for 3 years, so daily therapy for 3 years, and patients are monitored with routine CAT scans and lab work.

For patients who don't have an EGFR mutation, we do recommend broad panel testing. Of course, this is not the standard, but I think it's important for us to identify patients who may not benefit from immunotherapy. Patients that have an ALK mutation, for example, or ROS1 translocation, may not have the best chances of responding to adjuvant immunotherapy, and therefore, I think testing should be performed to make sure that we are having a shared decision-making conversation with our patients about the use of the correct adjuvant options.

In terms of adjuvant immunotherapy, we now have 2 approved agents. One of them is atezolizumab, and the other one that was just recently approved is pembrolizumab. Atezolizumab was approved on the basis of a large clinical trial called the IMpower010 study, which randomized 1,280 patients with stage IB to IIIA non-small cell lung cancer to either 1 year of atezolizumab or best supportive care. Of note, all of these patients had to have had adjuvant chemotherapy that included a cisplatin platinum chemotherapy. In the first analysis, we found that the disease-free survival or the probability of the patients remaining cancer-free was significantly improved in those patients that had a tumor expression of PD-L1 greater than or equal to 1% and received atezolizumab compared to patients who did not receive atezolizumab.

On the basis of this positive primary endpoint, the U.S. FDA approved the use of adjuvant atezolizumab for patients with stage II to IIIA resected non-small cell lung cancer after surgical resection and adjuvant chemotherapy. Recently, we heard that this does lead to small but significant improvement in overall survival. There is a trend towards improvement in overall survival. However, the data are quite immature at this point, and we do need longer follow-up to be able to follow this trend. The greatest magnitude of overall survival benefit was found in patients who had the PD-L1 greater than or equal to 50%. So it's important to know what the PD-L1 level of a patient may be when I'm thinking about adjuvant immunotherapy because adjuvant immunotherapy is most likely to benefit those that don't have an actionable mutation, such as EGFR, and those that have the highest PD-L1 staining, at least in the IMpower trial.

Secondly, the PEARLS clinical trial is a clinical trial that evaluated the use of pembrolizumab, which is another immunotherapy agent, again, in the adjuvant setting. For this clinical trial as well, there was a small but significant improvement in disease-free survival, again preventing the probability of recurrence in all patients that received pembrolizumab compared to the best supportive care. And basically, this led to also an approval by the FDA for the use of pembrolizumab. Again, now we have 2 options. Both of these are administered for 1 year.

What should patients know about therapy? These drugs are usually administered once every 3 weeks. They are given intravenously. Sometimes, we can change the treatment schedule to be either once every 4 weeks in the case of atezolizumab or every 6 weeks in the case of pembrolizumab. These may be associated with some side effects. Immunotherapy side effects that are most common are fatigue, chills, myalgias, or basically a feeling of pains in the body or joints.

But also, some serious life-threatening reactions can occur such as activation of the immune system to such an extent that the immune system may start to attack the body's organs. So this may lead to swelling or inflammation in the organs that may manifest itself as colitis if the gut gets inflamed, or pneumonitis if the lungs were to get inflamed, or pancreatitis if the pancreas were to get inflamed. Any organ in the body can really get inflamed. We've certainly seen cases of thyroiditis. We've seen cases of polyarthritis. We've seen cases where the brain may also get inflamed or the pituitary may get inflamed. So there are definitely some life-threatening reactions or side effects that can occur with the use of immunotherapy that should be closely monitored. The benefit of having used immunotherapy in the metastatic setting is that now we have a lot of experience managing these side effects. And if recognized early, these side effects can be managed appropriately with the use of steroids as well as holding therapy. Many of the times, we can even reinstitute immunotherapy without significant harm to the patients. However, I think immunotherapy benefits as well as side effects should be discussed in detail with the provider, especially in the adjuvant setting.

Patients may ask if neoadjuvant immunotherapy along with chemotherapy is a better approach compared to adjuvant immunotherapy. At this time, we don't have a clinical trial that is comparing neoadjuvant chemoimmunotherapy followed by surgery to an approach that is surgery followed by adjuvant immunotherapy. In general, I would say that if the decision by a multidisciplinary team has been made to proceed with surgery, careful discussion should be had about adjuvant chemotherapy as well as the use of adjuvant immunotherapy, and molecular testing should be performed. All patients with early-stage disease should have a multidisciplinary tumor board discussion, which includes engagement with surgeons, radiation oncologists, pulmonologists, pathologists, and medical oncologists so that they can ensure that many experts have had the chance to weigh into their case as well as come to the right conclusion on whether or not to use new adjuvant chemoimmunotherapy or just to proceed with surgical resection.

ASCO: Thank you, Dr. Aggarwal. You can learn more about neoadjuvant and adjuvant treatment options for early-stage non-small cell lung cancer at www.cancer.net/lung.

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In this podcast, Dr. Allison Kurian and genetic counselor Kristen Mahoney Shannon talk about what people should know about genetic testing and hereditary breast cancer, including what to expect when meeting with a genetic counselor, ways to reduce your risk of developing cancer, and talking about genetic test results with family.

 Dr. Kurian is a Professor of Medicine and of Epidemiology and Population Health at Stanford University School of Medicine, and Director of the Stanford Women's Clinical Cancer Genetics Program. She is also the 2023 Cancer.Net Specialty Editor for Breast Cancer.

Ms. Shannon is a senior genetic counselor and Director of the Cancer Center Genetics Program and Director of Genetic Counseling for the Massachusetts General Hospital Department of Medicine. She is also a 2023 Cancer.Net Advisory Panelist.

View disclosures for Dr. Kurian and Ms. Shannon at Cancer.Net.

Dr. Allison Kurian: I'm Allison Kurian. I am a professor of medicine, oncology, and epidemiology and population health at Stanford University. And I am speaking today with my colleague, Kristen Shannon, who will introduce herself.

Kristen Shannon: Hi, it's great to be here. My name is Kristen Shannon. I am a genetic counselor and the director of cancer genetics at Massachusetts General Hospital in Boston. And I have no financial relevant disclosures to report.

Dr. Allison Kurian: Thank you, and I have no relevant financial disclosures either. Very good. So today we will be talking about breast cancer and inherited risk and genetic testing. And let me start by providing a definition of a genetic or hereditary condition. So the way we think about this is something that has a high risk for developing a disease, not a certainty, but a high risk, and runs in families, generally because of a genetic finding that we can identify. And that typically is identified through sequencing, testing of blood or saliva samples, and typically allows us to find a change that we know is clearly associated with disease. A good example for breast cancer are the genes BRCA1 and BRCA2, which some may have heard of, and we will talk about further. So that is just an example, and we will get into more of the details of this as we go on. But I think the point is something that runs in families often is seen with the trait, so for BRCA1 or BRCA2, that would be breast cancer or ovarian cancer, affecting people in every generation. And having what we call for these kinds of genes an autosomal dominant inheritance pattern, so inherited from either parent. And taking only 1 copy that is not functioning to give a person higher risk of the condition. So that's sort of a bit of the basics here on genetic or hereditary risk.

And just to give a sense of how common hereditary breast cancer is, we think that in general this may account for, I would say, somewhere between 5% to perhaps 10% of cases of breast cancer. And Kristen, please jump in and tell me if you think differently. But that would be my ballpark. And I think probably the majority of those are the BRCA1 and BRCA2 genes that I mentioned, although there are others that we are recognizing are playing more of a role than we thought, and we'll discuss those, too. So let me give you a chance to continue and respond, Kristen.

Kristen Shannon: Yeah, no, I totally agree. And I was thinking that maybe I could talk a little bit about some of the features that are suggestive that there could be one of these inherited breast cancers in the family, because recognizing these signs of hereditary breast cancer can be super important for early detection and prevention of breast cancer. So first, multiple cases of breast cancer within the family, especially among close relatives like parents, siblings, children, those can be a sign that the cancer is inherited. Another important sign is early age of onset of disease. So breast cancer diagnosed at a young age, typically before the age of 50, might point towards hereditary risk. And it's not always the case, but it's something to be aware of. Also, if there is a history of ovarian cancer in the family, especially if you see it in conjunction with breast cancer cases, that's a significant sign that there could be something inherited in the family. And while it's rarer, male breast cancer can also be associated with hereditary gene mutations. So if there's a history of male breast cancer in the family, it's definitely something to think about in terms of hereditary risk.

Multiple cancer types in the family can also be another clue. It's not always just breast and ovarian cancer. If you see a family history of both breast and ovarian cancer or pancreatic cancer or prostate cancer within the same family, that also might be a sign of an inherited cancer syndrome. For individuals of Ashkenazi Jewish descent, it's worth noting that they have a higher prevalence of certain gene mutations in specific genes, specifically BRCA1 and BRCA2, which Dr. Kurian has mentioned before. So a family of history of breast or ovarian cancer in an Ashkenazi Jewish individual should be noted as a higher sign that this cancer could be due to an inherited gene. And lastly, if someone has had breast cancer in both breasts, that's called bilateral breast cancer, and that might indicate hereditary risk.

It's important, though, to remember that it's not just about any single sign in isolation. You really need to take a look at the bigger picture and the bigger context of the family. So if you notice any of these signs in your family, it's a good idea to seek guidance from a health care professional, like a genetic counselor or a medical oncologist, and they can help assess the family's risk and recommend genetic testing if needed. Dr. Kurian, did I forget anything or leave anything off?

Dr. Allison Kurian: Perfect as always. I will just add a little bit here in terms of the specific gene names that we think about, because sometimes it helps people to have sort of a list in their minds, not that we expect you to remember the whole alphabet soup of these different genes. And let me just say that I think it's always a bit of a hodgepodge, some of these names. I used to wonder how people come up with these names, and often there's a bit of a history there. But I will just go through a few of them. We now have some practice guidelines, and they are basically put together by a group of experts who review all the evidence frequently and come up with recommendations. And so there is a list in these guidelines of basically which genes we think are appropriate to test for breast cancer in families, because there's enough evidence to suggest that.

And so in addition to BRCA1 and BRCA2, the ones that I think of as the most important, and I'll want to hear Kristen's thoughts about this, too, but the ones that we see most often are called ATM. Sounds like a cash machine, unfortunately not, but ATM. CHEK2, C-H-E-K-2, and then one called PALB2, which stands for Partner and Localizer of BRCA2, and is a lot like BRCA2 in its risks.

There are some other genes that give breast cancer risks that are less common. One of them, CDH1, is a gene that also causes an increased risk of stomach cancer. There are a few others that we always keep in mind. There's one called PTEN that's very rare that causes a syndrome called Cowden syndrome that I certainly haven't seen much of. Kristen may have seen more, but it's not something we see often and goes with a lot of other features in families. There are 2 genes that I think we recognize more in recent years and like to be sure we test, called RAD51C and RAD51D, and those both give increased risks. And then another one that I always think of as important here is TP53, and that is a gene that causes something called Li-Fraumeni syndrome, which has probably the highest cancer risks of which we know. There's another one, STK11, that gives some risk, NF1. We see these as being less frequent contributors. Those are the ones that I kind of keep in mind. And again, there will not be a quiz on the alphabet soup, but just so you're aware of what kinds of names you might hear. Kristen, please jump in if I've forgotten any or anything else you want to say.

Kristen Shannon: No, I think that that's important. I think the only thing that I would add is that some people think when they go in for breast cancer genetic testing, they only are getting the BRCA1 and BRCA2 gene. And it's just important for people to realize that that's not really a complete test at this point, as you mentioned, Dr. Kurian.

Dr. Allison Kurian: Totally agree, and thank you.

Kristen Shannon: Should we move into how to prepare for a genetic counseling appointment?

Dr. Allison Kurian: Please, yes.

Kristen Shannon: Sure, okay. So preparing for a genetic counseling appointment for breast cancer risk can be helpful. First and foremost, we suggest that you gather your family health history. So reach out to your relatives and compile as much information as possible about your family's health background. Pay special attention to any instances of breast cancer and ovarian cancer, prostate cancer, pancreatic cancer in the family. And if any family members have had genetic testing, it's really helpful to jot down those test results as well and bring them with you to the appointment. The other thing is to think about your own personal medical history. You know, think about if you've had any past diagnosis, any treatments, surgeries, or medical conditions, especially those related to breast cancer, your genetic counseling appointment will include a discussion of those. The other thing is, you know, if you've had any medical tests related to cancer, it's important to gather those records if they're not already in your hospital's medical record system that you are going to.

Another good idea is to just prepare a list of questions that you might want to have answered. So what do you want to know? Are there specific concerns or specific things you're curious about? It's also important to understand what you want to get out of this genetic counseling encounter. Do you want to just clarify your risk of having a gene? Do you want to consider genetic testing? Or do you want to talk about just managing your risk for breast cancer? That's super important to have that in mind before you actually go into your appointment. Lastly, I would consider bringing along a person, a supportive person with you to the appointment. Having someone with you can help provide emotional support because sometimes these visits can get emotionally charged, but it also can help to have someone remember important details that you will discuss with your health care provider. So it's really important to just arm yourself with information, questions, and support so that the appointment is as productive and informative as it can be. Do you have anything else you'd like to add, Dr. Kurian?

Dr. Allison Kurian: It's wonderful to have your expert perspective on this. And I guess any thoughts about really what's inside the box? I think sometimes people just sort of wonder what's going to happen when I go in that room. Sometimes we have patients come in and say, "What are you guys going to do to me? Will there be surgery done?" And we reassure them that we are not doing anything that wild. And so maybe just a sense of kind of walking people through what will happen when they go to meet with genetic counselors.

Kristen Shannon: Absolutely, thanks for bringing that up. So during the initial meeting, first you'll probably discuss your personal health history, again, any past diagnoses, surgeries, medical conditions. And then typically a genetic counselor or a medical professional will dive right into your family health history. So they'll ask a whole bunch of questions about your close and extended family members to build a really comprehensive picture of your family and the cancer diagnosis in it. They'll want to know if anyone in your family has had cancer, and they'll also want to know what type of cancer that person has had and also the age at which that person was diagnosed. So those are the 3 pieces of information that your health care provider will want to get from you.

The genetic counselor will also probably ask you about what you want to get out of this encounter to make sure that you're both on the same page. Again, do you want genetic testing? You know that already. Or do you want to just talk through the process?

So the big part of the initial meeting is really education. The genetic counselor will explain what Dr. Kurian described at the very outset of this discussion, what's the genetic basis of hereditary breast cancer, including all the specific genes that Dr. Kurian—the alphabet soup that we talked about. Talk about inheritance patterns and the implications of having a genetic mutation. The genetic counselor will probably also first assess your risk of having a mutation in one of the genes, and then they'll also talk to you often about genetic testing. So if genetic testing is on the table and you and the genetic counselor both agree that it's a good step, they'll walk you through the process of informed consent. And so this ensures that you understand what the testing entails, the potential outcomes, the implications of the test results.

And then if you decide to go through with genetic testing, you will provide a blood or a saliva sample. And then it's a waiting game because these test results can take several weeks, usually about 3 to 4 weeks to get the test results back. When the test results come back, you'll typically have a follow-up appointment, either in-person or on the phone with your genetic counselor. And that's when they spend a lot of time interpreting the test results, explain what they mean for you and your health, as well as discussing the appropriate risk management strategies, if necessary. And if a gene mutation is identified, a genetic counselor will guide you on how to manage these risks. But it will depend on the specific mutation that is identified. And then the other thing that the genetic counselor can help with is just the emotional support. Some people have a harder time than others hearing this information. And also to talk about how to tell your family members about this. So in a nutshell, the initial meeting with the genetic counselor is about gathering information, assessing risk, and potentially deciding on whether or not you're going to have genetic testing. And then after that step, it's about interpreting the test results, talking about next steps, and providing emotional support.

Dr. Allison Kurian: Thank you, Kristen. That was wonderful and very complete. And as I was listening to you, first of all, I was thinking about my general admiration for genetic counselors, which is huge. They taught me everything I know about this field. But so also kind of highlighting the key things that a meeting with a genetic counselor will do for you, as you so nicely did. And I think it's getting the right test ordered, making sure that the results make sense to you, and going beyond the patient. But I think those are sort of the key aspects that you communicated really well of the things that we want to get done there.

Kristen Shannon: Well said, well said. And I couldn't agree more.

Dr. Allison Kurian: And what do you think about the family part in terms of how that gets done?

Kristen Shannon: Right, so discussing your genetic test results with family members can be hard and challenging, but it's really, really important. In terms of talking to your family members, I think first, determine the way you're going to notify your family members. So are you going to talk to them? Are you going to send them a letter or an email? And how you share the information may be different based on your relationship with that person. So for example, you may sit down over coffee with a close family member to talk about your test results, but you may choose to write a letter to someone that you don't have that much contact with.

The next thing that I think is really important is to be prepared. So before you even start to have this conversation, make sure that you have a clear understanding of your genetic test results, the implications to you and to the family member. That's super important before you even start to have the conversation so that you can explain things to people in simple terms without too much medical jargon and make sure you keep it straightforward. It's really helpful to have a copy of your genetic test results and to provide that to your relatives if you're comfortable doing so, because then they can take that information with them to their genetic counseling or genetic testing appointment, which can be incredibly essential in terms of making sure that they get the correct test at the right time and the test results are interpreted correctly.

The only other suggestion I have is just to keep in mind that family members are going to react very differently to this information. And some people will be very matter of fact about it. Some people might get a little distracted by this whole thing. So just to be patient with people and keep the conversation open. Allow them to call you if you're willing to do that so that the conversation can develop over time because, you know, really, in the end, the goal is to make sure that everyone in the family is well informed and makes decisions based on their own health and their well-being.

Dr. Allison Kurian: Thank you. I couldn't agree more. And we sometimes, as people may have heard, call this "cascade genetic testing." So a patient is tested. Somebody who's already had cancer maybe is tested. But then we have the opportunity to have this cascade of beneficial genetic testing, where we can get to people before they have cancer and work on prevention and screening, which I'll talk about in a minute. And I will say that, in general, we here in the United States, and certainly other places as well, don't do as well as we would like with cascade testing despite all best efforts of everyone. And so just to emphasize that family notification is super important, genetic counselors are wonderful at helping people to do that. And I think also additional strategies and interventions are underway to try to help make that easier.

So if I may, I'll talk just a little bit about kind of what we do when we find something. Is that okay to do?

Kristen Shannon: That sounds great. Talk about people, you know, what they can do about their test results.

Dr. Allison Kurian: Good. Yeah, so I always think that's important. I'm an oncologist by training. I'm not a geneticist. And again, it's only thanks to the brilliance of genetic counselors like Kristen that I have learned what I have for the last 2 decades working in the field. But so I tend to think in terms of what can we do to treat this person differently if they have cancer to prevent or reduce the risk of a future cancer. And so what I would say is increasingly over the last few years for a person with breast cancer, as well as some additional cancers, it started to matter what these results are in terms of how we treat the person, whether we might give different medications. And that's really exciting because for years in this field, we didn't have that, and now we do.

And so the drugs that are increasingly important are called PARP, P-A-R-P, inhibitors. And sometimes, if a person has a BRCA1 or BRCA2 gene mutation, we might even offer those drugs to treat a breast cancer or, in other cases, ovarian, prostate, or pancreatic cancer. So I think the testing can matter like never before in terms of what we might do to take care of people's cancer. Sometimes we might also choose a different surgery. So sometimes a woman who has a diagnosis of breast cancer might choose to do a more extensive breast surgery, she might choose a double mastectomy to reduce her risk of getting a second breast cancer. That's never required. She certainly doesn't have to do so extensive a surgery if she doesn't choose, but it is an option that some people might choose. And there might also be other cancer risks to manage in somebody who had breast cancer. BRCA1 and BRCA2, for example, give a high risk of ovarian cancer. And so we might talk with someone about the possibility of removing ovaries to prevent an ovarian cancer, which often is recommended with BRCA1, BRCA2, and other such gene mutations.

I will say that I think for somebody who hasn't had cancer yet, or hopefully ever, particularly as we think about breast cancer, we're often thinking about intensive screening. So starting often earlier than a person would if she didn't have high risk and generally adding magnetic resonance imaging, MRI, to screening with mammogram alone. And that really is, I think, the cornerstone for women at high risk is adding that breast MRI screening. For pretty much all of the genes I mentioned, that would be clinically indicated and covered by insurance and important to do. MRI has no radiation, very effective at finding breast cancer early.

So I think to summarize, it's really all about understanding risk based on a particular gene mutation, understanding if a different kind of treatment is needed for the cancer that a person has, understanding if any sort of preventive measure is needed for future cancer risk, and making sure that the screening we have for breast and for other cancers is appropriate to the level of risk. Anything to add there, Kristen?

Kristen Shannon: No. No, I think that that's great.

Dr. Allison Kurian: Absolutely. Yeah, so I think it's wonderful to have this opportunity to speak about the importance of genetic testing, which is I think more important than it ever has been at this time for the care of patients with breast cancer and their families. And so as we move into breast cancer awareness month, it's great to be able to talk about this. Thanks so much.

Kristen Shannon: Thank you so much. I agree. And if you have any questions, I would suggest you reach out to your doctor or look up on the ASCO website for a referral to a genetic counselor.

ASCO: Thank you, Dr. Kurian and Ms. Shannon. Learn more about hereditary breast cancer and genetic testing at www.cancer.net/hboc.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this Meaningful Conversations podcast, Dr. Lalan Wilfong talks with social worker Lydia Mills about what people with cancer should know when discussing their goals of care with their health care team, including the ways it can help inform their treatment plan and tips for navigating the conversation.

Meaningful Conversations is a Cancer.Net blog and podcast series that describes the important discussions people may need to have with their providers, caregivers, and loved ones during cancer and offers ways to help navigate these conversations.

Dr. Wilfong is a medical oncologist and the senior vice president of payer and care transformation at the U.S. Oncology Network. He is also a member of the 2023 Cancer.Net Editorial Board. Ms. Mills is a licensed clinical social worker and the senior manager of supportive care services at the U.S. Oncology Network. 

View disclosures for Dr. Wilfong and Ms. Mills at Cancer.Net.

Dr. Wilfong: Hi, I'm Dr. Lalan Wilfong, Senior Vice President of Payer and Care Transformation for the U.S. Oncology Network. And today we're going to be talking about goals of care. Lydia, can you introduce yourself?

Lydia Mills: Yeah, sure. I'm Lydia Mills, Senior Manager, Supportive Care Services. I work with practices across the U.S. Oncology Network, and I am a licensed clinical social worker.

Dr. Wilfong: So Lydia, what does it mean when we talk about goals of care during cancer?

Lydia Mills: Well, I think a lot of people think about what treatment is going to look like, what that prognosis is going to look like, what that end goal is going to be when they're having their treatment. I think it can be a lot broader than that. In fact, I've had some people say, "What do you mean by goals of care?" So I think it's really important to bring in, I think, the patient perspective when we're talking about this and what's important for them in addition to maybe what that cancer treatment is going to do for them physically, but also what is important to them as far as what do they want to work, are there things they want to accomplish, are there things they want to get done, are there things they want to do or see? As well as, you know, often the goal quote is to be cured, and we know that's not always the case. So what are some other things that they might want to accomplish? And, you know, I don't know from your perspective from a physician, but that's kind of what I saw with social work is kind of more what's really important to them.

Dr. Wilfong: Yeah, it's so important for people undergoing treatment for cancer to have an understanding of what they're going through. I've seen patients all the time, you know, at the end of life, look at me and go, "I wish I would have made a different decision." And that's always super hard as a physician to realize that you didn't take the time to fully understand what a patient wanted. And they went through something that they made a different decision about if they had known better. And so I think it's so important to talk about that with patients so they truly understand what treatment they're getting, what the impact of that is on their quality of life, what the duration of improvement and survival and things is. Because like you mentioned, a lot of people take therapy thinking that they're going to be cured, and we know that's not going to be the case many times. So they can really understand and make sure that they're doing things that are appropriate for them, and that are aligned with what they really want to accomplish for the time of life that they have. So it is super important about that. Any other things that you think of that are important around the goals of care for people with cancer?

Lydia Mills: Well, you know, I think a lot of times when people start thinking about, well, I need to really think about getting quote things in order, right? They often think more of the financial piece. What am I going to do with my assets? They don't always stop to think about family members, relationships. Even, gosh, it's really important that we take that family trip in 6 months. You know, sometimes they just don't even always think about all those things. So I know I would always try to bring that into perspective as well, that it's not always just about, you know, the treatment and what that's going to look like and your financial aspect. But what are a lot of these other things that are important to you, your family, and your loved ones?

Dr. Wilfong: I know so many times people have these life events that they want to make sure that they are at, whether that's a wedding or a birth of a child or things. And being able to plan appropriately for that is so important. I just remember a story I heard from one of my physician colleagues recently where a patient who had a terminal illness was going to get married, and they really wanted to get married is a big thing, and they kept putting it off and putting it off. And finally, she convinced them to actually get married. And the spouse, after the patient had died, was so appreciative of the physician pushing them to get that done because it meant the world to him and to her to have that actual wedding event. And so just things like that are so important for patients to understand and so they can plan for their lives. So Lydia, when do you think these conversations should take place?

Lydia Mills: I honestly think the earlier the better. I mean, I think sometimes people want to wait and kind of see how things are going. And there might be an initial discussion when they're first diagnosed and treatment first starts. But I really think the earlier you can start talking about this and then keep checking in with the patient. And I would encourage patients to let those physicians know, like, hey, I really want to do this trip, or I really need to make it to graduation, whatever that might be, because depending on what that trajectory looks like, things change so frequently, or they can. And so, if you have kind of set milestones in your head of when to have the conversation, that may not always work for the planning for the patient and their family.

Dr. Wilfong: I completely agree. I think early and often is a phrase I like to use. And it changes, like you mentioned. I mean, people with cancer undergoing therapy, things change, their life changes. And so making sure that you're always going back to my aligning the treatment that we're giving to their goals of care is so important because it changes all the time. And I think that's one thing that we get hung up on, especially as physicians. We think these conversations have to be this long, drawn out, hour to hour long discussion with patients, which there's a role and a time for that. But many times, it's just that simple check-in of, are we still on the right track? Has anything changed with you that we need to address and make sure that we stay on top of that?

When we're having these conversations with patients, what typically is discussed? I mean, what do you think the main topics that a patient should expect to discuss during one of these?

Lydia Mills: Yeah, well, I mean, I think, and you can chime in from a physician perspective, but I think a lot of times it is, you know, what is this treatment going to look like? How is it going to affect you? Of course people often want to know about prognosis. Again, I think it's important to expand on that and find out, you know, what is important to the patient. If you're going to be on treatment for, you know, 6-plus months or longer, tell me what do you have going on? Do you have things scheduled? I think people are afraid often to interrupt their treatment so they don't want to talk about what's important to them. They want to make sure they're there every single treatment visit versus, you know, I really did have this trip planned or there's a life event occurring. They can usually take a break if the physician knows, right? So I think it can be a variety of things, but you know, definitely what it might look like in the next few months and sometimes it's hard to go beyond that, which I think brings in the why it's important to have these conversations frequently.

Dr. Wilfong: I agree. And I see so many times people don't want to talk about this stuff for themselves. It is so important for us to understand really what is important to them so we can give them the right therapy. And I would say I think people need to bring their open and honest self to these conversations so that the things that may be bugging you in the back of your mind, we want to make sure we get those out there and talk about them because I can't help you unless I know what's going on with you. So I think that's really important as well. These are hard discussions. I mean people are having to open themselves up, which is hard for a lot of people to do, to really talk about your goals, your fears. Lydia, how do patients come and bring themselves to these conversations? What can they do to prepare so that they're ready to have these?

Lydia Mills: Yeah, you know, I think it's really important. You know, a lot of times patients, like I mentioned, they're used to talking about how they're doing physically, their pain, their nausea. They're not always used to bringing up, oh, and by the way, this is what's important to me. So I think even just writing a list. I encourage people to keep it brief and concise, but have some bullet points to help you remember, and saying, gosh, thank you so much for telling me what this is going to impact. I want you to know that, you know, whatever it might be, I have this event coming up, or I would really like to take a break so I could spend a week at the beach with my family, or whatever that might be. Making those bullet points if you have questions, concerns, anything that you want to know, but make it brief, concise, and to the point. You may not get through everything that visit, but you know, at least the provider knows, and you can kind of preface it with saying, hey, I have a couple things I'd like to talk about today. It's always okay to say that. I just think sometimes patients are, like you said, they're a little hesitant to do that.

Dr. Wilfong: Yeah, no, I know it's—you go into the doctor's office, your mind goes blank. And so definitely having a list, writing things down, thinking through that ahead of time is important. And I know as a physician, many times, I'll broach a topic with a patient, they may not be ready that day. And I think it's important for us to, as the health care team, to make sure that we know the next time you come in, I really want to talk about these things so that they can have some time to prepare. Which brings me to, you know, what is the role of caregivers and loved ones in these conversations? Should they come, should they not come? Should you talk to your family? What do you think?

Lydia Mills: Ideally, if you're able to bring someone with you, now I know with the pandemic, some of that's changed a little bit, but it's great if you can bring at least somebody with you so that you can have other eyes and ears. And honestly, I think for that loved one, the family, the caregiver, at that point, maybe to ask some clarifying questions, but really to sit back and listen, hear what that patient has to say. It's not really a time to interject what you think and what your hopes are, it's really a time for the patient to be able to share with their loved one and the physician, like this is what is important to me. And so I always encourage the loved ones to be there, but so that they can hear and, you know, be able to better understand.

Dr. Wilfong: And I can't tell you how many times patients have told me they're doing something because of their loved one. When you actually talk about it with the loved one, there's a disconnect there because they're not talking about the stuff at home. And just having those conversations and having the team help facilitate some of those conversations sometimes helps the loved ones be able to come together better because, you know, I don't know about y'all, but my wife and I, very commonly we have different thoughts about things, but we never actually say we have different thoughts until it leads to some sort of conflict. I don't know what that says about me and my marriage, but hopefully I'm not the only one that does that. But it's very similar, and especially in a time like this, which is so stressful to get that alignment together. Because people tend to be more aligned than they think, and they make assumptions about the other person that until you have those conversations will remain assumptions. You may not be on the same page. Speaking of that, who in the health care team typically is involved in these conversations, Lydia?

Lydia Mills: The first thought people often think, you know, the physicians, maybe that advanced practice provider, if it's a nurse practitioner, physician assistant. But as a social worker, clinical social worker, I was involved in these conversations a lot and helping to facilitate not only between the patient and their loved ones, but with the providers as well. But, you know, I think sometimes people aren't necessarily, they don't really think that they're involved in these conversations, but I always encourage the whole health care team to be aware and to listen, because nurses, the infusion room, on triage, medical assistants, even the lab, patients share a lot of things. They get to know these people well, and they'll share a lot, and that's a good time to say, gosh, have you mentioned this or talked about this with your provider? Encourage that conversation. So I think in some ways, the whole health care team can be involved in these conversations.

Dr. Wilfong: You're right. When I started down on oncology many years ago, I always felt like I had to do everything myself, that I was the physician, it was my responsibility to manage all this myself. But I learned very quickly, thankfully had a very good care team that surrounded me and the patients, realizing that everybody had different skillsets. My skillset as a physician was managing the cancer, managing symptoms, you know, really understanding prognosis and things like that, whereas the care team was so much more skilled at helping with some of the other things that I'm not skilled about. Like social workers is a great example, Lydia. Can you talk a little bit about what social workers actually bring to this conversation?

Lydia Mills: People are often, when they come to the office, they're used to talking about their physical side effects and symptoms. And it's a great opportunity to say, but how are you feeling about this? You know, emotionally, tell me what is going on with your thought process here. And that's often where you start hearing about, you know, I'm afraid to leave my loved ones, I worry, I don't want to be a burden. You know, I have this important life event happening. That's often where those conversations would happen because I would allow that space. But like you said, my skillset is different, and that's where my focus is, is more how are you feeling, where are you mentally and emotionally with this process.

Dr. Wilfong: And many times I've found that we start involving people even outside of what we think of the traditional health care team. A lot of patients have religious issues when they're dealing with a serious illness like cancer. And I can't tell you many times I've referred someone back to their local priest or chaplain or pastor to have some of those conversations that I'm not trained to do, but they are, and help them through some of that part as well. So, and even like lawyers and figuring out forms and documents to make sure that your assets and your wishes are done. It involves much more than just the health care team to do that. So Lydia, if a physician in a health care team is not really talking about this to a patient, they really want to talk about it, how do they approach us and get these conversations started? Any hints or tips?

Lydia Mills: Yeah, like I said earlier, I think jotting your thoughts down so that it's clear when you, you know, you can remember when you get into the office and just saying, you know, hey, I have some questions for you or some things that have been on my mind that I would like to discuss. If there's someone from the health care team that can be invited in to help facilitate, sometimes that is helpful. I know as a social worker, I used to do that quite often, but patients and their families can absolutely do it themselves, and it's okay. Again, sometimes the provider is so focused on these are the next steps, but it's not that they don't want to hear this information. It just doesn't always come naturally to think, to say, oh, and what else might you have that's not related to your side effects that you want to share with me? So I encourage people just to make sure they have kind of clear in their mind what they want to talk about because physicians' time is limited. And then just say, hey, I have a few things I'd like to talk about with you as well.

Dr. Wilfong: I agree, and great call out on how do you ask the other care team members. I mean, if you're sitting in an infusion room for a few hours, your infusion room nurse has a wealth of knowledge and support and potentially can raise things to the physician that you may not feel comfortable raising to them. I've had that happen many times as well where my nurse will come up to me and go, "Did you know Ms. So-and-so needs to talk about blah, blah, blah?" I'm like, "Oh no, but we will." And so that care team approach can be really valuable. I think coming prepared with questions and comments as well, I mean, feel free to ask, what is this chemotherapy going to do to me? What are the side effects? What can I expect? Is there anything long term that's going to be a problem for me? Can I go back to work? Things like that. Any other thoughts about questions that people could potentially bring, Lydia?

Lydia Mills: Yeah, and you know, I think it's a great opportunity, because I would have some patients who were afraid to bring up to their physician that, you know, maybe they don't know if they want to continue treatment, or even pursue that, you know, next idea of treatment. So asking questions, pointed questions such as, well, you've told me what it's like if I'm going to have treatment and what to expect. What if I were to not have treatment? What might that look like? Or what if I only do it for a short amount of time? And you know, physically, what might that look like for me? Or if I don't pursue treatment at all, what might that look like for me? And I think sometimes, again, people are afraid to raise those questions, but they're very valid questions because sometimes the focus is on treatment, and maybe that's not what that patient wants to do.

Dr. Wilfong: I think you said it really well earlier when you talked about providing space. I think it's important for us as health care providers to provide the space for people to have these conversations, to initiate these conversations. But then I think it's also important for patients to feel comfortable having space with their caregivers, their loved ones, to have these conversations as well. So Lydia, any final thoughts or takeaways that we should leave folks with?

Lydia Mills: No, I just think from a patient perspective, don't be afraid to bring up the topic. And from a provider perspective, I don't know how you feel about this, but I think even those patients that have maybe curative intent, it's still important, I think, to have a conversation about what they're hoping to get from this treatment and what they might have planned, depending how long that treatment may last. Because I will tell you, it's mortality that comes to everybody's mind after diagnosis, you know, even with a curative intent. And so I just think it's really important, again, to bring this up with all patients. What is important to them? What are their hopes to get from this or not get from this?

Dr. Wilfong: Well, thanks, Lydia. I learned something from you every time we talk about this topic. So I appreciate the time. And definitely encourage everyone to have goals of care discussions with your physicians and health care teams. It's important.

Lydia Mills: Absolutely. Thank you.

ASCO: Thank you, Dr. Wilfong and Ms. Mills. Find more podcasts and blog posts in the Meaningful Conversations series at www.cancer.net/meaningfulconversations.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Abby Rosenberg discusses what parents and family members of children with cancer should know about palliative and supportive care. She addresses the way palliative and supportive care is different from hospice or end-of-life care, what to expect when meeting with the palliative and supportive care team, and the ways this type of care can support children with cancer and their families.

Dr. Rosenberg is the chief of pediatric palliative care at the Dana-Farber Cancer Institute and Boston Children's Hospital in Boston, Massachusetts.

View Dr. Rosenberg's disclosures at Cancer.Net.

Dr. Rosenberg: Hi, my name is Abby Rosenberg. I am the chief of pediatric palliative care at the Dana-Farber Cancer Institute and Boston Children's Hospital. And today we're going to be talking about what pediatric palliative care is, maybe demystifying it a little bit, and more importantly, talking about how it can help kids with cancer and their families.

I think one of the most important things to know about palliative care is that it is a specialized kind of medical care for people who live with serious illnesses like cancer. And folks who are receiving palliative care are receiving extra support to help them with complicated symptoms, pain, distress, as well as complicated decisions that they might need to make in the process of their illness.

Palliative care is really intended to help enhance a person's current care by focusing on their quality of life, and not only the patient's quality of life but also the quality of life for the whole family. In pediatrics, that includes parents, siblings, and other kids who might be members of the community. The way I think about palliative care is that it is really intended to help people live their best lives for as long as possible. And so with that in mind, it can really help a whole bunch of people who are affected by pediatric cancer.

And the way we do that is by delivering help through what we call an "interprofessional team." And so a palliative care team in pediatrics includes physicians, it includes nurses, includes advanced practice providers like nurse practitioners, it includes social workers. It may also include child life specialists, psychologists, chaplains, other folks who are involved in the child's overall well-being.

Palliative care can be provided at any time in a child's cancer experience and anywhere. It can be delivered while you are in the clinic, while you are in the hospital staying overnight, and we can deliver it to you at home.

Some people confuse palliative care and hospice care, and those are 2 different things. So palliative care can be delivered concurrently with cancer-directed and cure-directed therapy.  And generally, when we talk about hospice, it is for patients and families who have started to understand and recognize that perhaps their cancer might not be curable, and they are making the courageous and loving decision to switch gears and focus more on quality of life without continuing cure-directed therapies. Hospice care, like palliative care, can be delivered in a bunch of different settings. And most times in pediatric hospice care, we think about delivering it to a child in their home and within their home community.

Some of the things that parents often ask us when we're talking about palliative care for their kids with cancer is, how do I know if my child is ready? And how do I ask for it? The answer to the first question is that again, your child can be ready for palliative care at any time. And it's really intended to help you navigate the heart of having a child with cancer. And that can, again, include anything from making complicated decisions, processing complicated information, making plans for you and your child's future, and managing complex pain and symptoms. How you ask for it is in most pediatric cancer centers, there is an embedded palliative care team that can help you. So you can ask any of your doctors and nurses and other folks who are taking care of you and your family.

The last thing I'll say about palliative care is that it is a subspecialty team of experts who are good at all of these things like communication and pain and symptom management. Most pediatric oncologists do what we call primary palliative care, and that is they help support you in all of these things, too. So they help talk to you about complicated decisions and upcoming plans. They help talk to you about what might be coming with your child's symptoms, and they really help you navigate the cancer experience. And so what we try to do in pediatric palliative care is partner with you and your oncology team so that we just become a bigger team, thinking more holistically about all of the ways we can support you and your family. I think, in the end, the message of all of this is that every person taking care of a kid with cancer is trying to help that kid to thrive. And pediatric palliative care can be a really important resource to help kids to do that to the best of their abilities.

So another question that we can hear from parents and families is what to expect when the palliative care team gets called. I think at a minimum, the expectation is that you will meet more people who will be really curious about your family and your child. They will ask a lot of questions about what matters to you, what are your values. They'll ask you questions about what is happening with the child's illness, what are your worries, what are your hopes, and what they do with all of that information is they help you process it, and they help translate it into something that can work for your child's overall cancer care. Part of meeting a palliative care team is always meeting all of these different members of the team, so you'll meet doctors, nurses, nurse practitioners, social workers, perhaps chaplains, child life specialists, psychologists, all of the folks that I previously mentioned. And the reason we have those big teams is because we recognize that each member of that team can help you with a different part of your whole cancer experience. And so for example, if your faith and your spiritual community is a really big part of how you are coping with being the parent of a child with cancer. We want to connect you with that part of your own strengths and resources and figure out how to support you while you are under our care in the hospital setting.

So one other thing that pediatric palliative care teams can help with is talking within your family. So sometimes we get questions about how do I talk to my child about what's happening, or how do I talk to my child's brothers and sisters about what's happening? Maybe it's a, how do I support their brothers and sisters? It could be about the challenges of being a parent with one kid in the hospital and others at home, and how do you maintain your identity as a parent? How do you still be a good parent to a large family when you have one child who's really sick with cancer? And we in palliative care really can help you with that with all of the different resources and team members that I mentioned, and we can help you talk to your other kids. We can help your kids talk to each other. We can help you think as a parent about how you can navigate the situation that no parent could ever have planned for until they're in it. The other thing that we do within palliative care and the other thing you can expect is we partner very closely with your oncology team, not to replace them or make decisions on their behalf, but more to help them know you better. And so what we do is we talk together about what we are hearing from you, about what your child might need. We provide advice, we provide recommendations, for example, for how to manage perhaps complicated symptoms. We might have conversations with you and your oncologist together in the room to think as a bigger team about how we can support your child's well-being. And we'll often ask you questions in the midst of all of this about what you think is important for your child, how you want to spend your time, how you define your child's quality of life, and how we, as a larger program, taking care of children with cancer, can do better to make sure your kid is thriving for as long as possible.

ASCO: Thank you, Dr. Rosenberg. Learn more about palliative and supportive care at www.cancer.net/palliative.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

The theme of the 2023 ASCO Annual Meeting was "Partnering With Patients: The Cornerstone of Cancer Care and Research." From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today's episode, our guests will discuss new research advances in treating non-small cell lung cancer, small cell lung cancer, and mesothelioma. 

Dr. Charu Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the 2023 Cancer.Net Associate Editor for Lung Cancer.

Dr. Melina Marmarelis is an assistant professor at the University of Pennsylvania, the Medical Director of the Penn Medicine Mesothelioma Program, and the co-director of the Molecular Tumor Board at the University of Pennsylvania. She is also the 2023 Cancer.Net Specialty Editor for Mesothelioma.

Dr. Kristin Higgins is a radiation oncologist, Professor and Vice Chair in Clinical Research in the Department of Radiation Oncology at Emory University School of Medicine and medical director of radiation oncology of The Emory Clinic at Winship Cancer Institute's Clifton campus location. She is also a 2023 Cancer.Net Advisory Panelist for Lung Cancer.

You can view disclosures for Dr. Aggarwal, Dr. Marmarelis, and Dr. Higgins at Cancer.Net.

Dr. Aggarwal: Hello and welcome to this Cancer.Net Research Round Up podcast. Today, we will be talking about the latest research from the Annual Meeting of the American Society of Clinical Oncology from June 2023, and I'm joined today by 2 experts in the field of lung cancer. Before I introduce them, I'd like to introduce myself. I'm Dr. Charu Aggarwal. I'm an associate professor for lung cancer excellence at the University of Pennsylvania's Abramson Cancer Center. I'd now like to introduce Dr. Melina Marmarelis.

Dr. Marmarelis: Hi, so happy to be here. I'm Melina Marmarelis. I'm an assistant professor at the University of Pennsylvania and the medical director of the Penn mesothelioma program.

Dr. Aggarwal: And Dr. Kristin Higgins.

Dr. Higgins: Hi, everyone. I'm Kristin Higgins. I am a thoracic radiation oncologist at Winship Cancer Institute of Emory University. I'm a professor and vice chair for clinical research for radiation oncology.

Dr. Aggarwal: Fantastic. So today, we'll talk about relevant research as it applies to practical implications in the clinic for practitioners, but most importantly, patients with lung cancer. I'd like to start off by discussing 2 key studies, and I would love for perspectives from our faculty here. The first study I want to highlight is the ADAURA trial. This is a trial that has already sort of changed practice in most recent years when the study was presented at the Annual Meeting of the American Society of Clinical Oncology in 2020, but we have new updates on this study as of 2023. So, in brief, this was a study that looked at the value of administering an oral pill called osimertinib that is a tyrosine kinase inhibitor against the EGFR, or the epidermal growth factor receptor, in patients with non-small cell lung cancer.

We know that non-small cell lung cancer is quite a heterogeneous disease with some subsets of patients having mutations that may render them increasingly sensitive to the effects of these tyrosine kinase inhibitors. In fact, these pills have been used in the metastatic setting for several years based on an improvement in overall survival. What the ADAURA study tried to do was ask the question if this pill would add an incremental advantage after receiving curative-intent surgical resection in those with early-stage lung cancer. So this study enrolled patients with stage IB to IIIA non-small cell lung cancer after surgical resection and focused only on those patients that had sensitizing EGFR mutations with EGFR exon 19 deletion or L858R mutations. Patients could receive chemotherapy after having the surgery and then were basically randomized into 2 groups, one of whom received osimertinib at a dose of 80 milligrams once daily for a total of 3 years. Patients were followed up for recurrence.

We already know from the earlier results that patients who received osimertinib had a better chance of delaying the recurrence of disease. However, what we found at the Annual Meeting this year is that the administration of this osimertinib also improved overall survival, which is really what we all look for in the oncology world. If you're administering a therapy, especially for a long duration, we want to be able to see a survival benefit, and that's what we saw. In fact, in patients who received osimertinib, there was a 49% less likelihood of dying from lung cancer compared to those who did not receive osimertinib. This, I think, is practice-affirming. It may not be practice-changing because some of the practitioners started using osimertinib after its FDA approval in December of 2020, but I think it just confirms our practice as it delivers an overall survival advantage in these patients. One thing that's increasingly important is to identify patients who have this mutation, so now we have efforts underway locally as well as nationally to perform molecular genotyping on all patients with lung cancer so that we can adequately and appropriately treat those with early-stage lung cancer following curative resection or following surgery. Melina and Kristin, what are your thoughts?

Dr. Marmarelis: Well, I think these results are really important because it did, as you say, affirm kind of what we're already doing, but I think the most convincing part of this for me is the prevention of spread of disease to the brain. This is not comparing osimertinib after surgery versus osimertinib ever, which I think is a difficult part about interpreting this trial. But I think the fact that it prevented disease from going to the brain is really meaningful to everyone, to patients, to the physicians that are caring for them, so I think that's a really important endpoint.

Dr. Higgins: I agree with Melina. I think this is really exciting for our patients. It's exciting to have more treatment options for early-stage lung cancer. I think patients that are diagnosed with early-stage lung cancer are highly motivated to do everything they can to improve their likelihood of being cured. So I tend to have a lot of conversations about side effects and toxicities with patients that have questions and are sort of wondering how it will affect their quality of life, and of course, that is an important piece of it because patients that do have curable lung cancer are probably starting off with a better overall quality of life, but I think generally speaking, our patients have tolerated it well. I'm also kind of excited from a radiation oncology point of view. We treat patients with stereotactic body radiation therapy [SBRT] that are medically inoperable. And we have another trial with a cohort looking at osimertinib for those patients that have EGFR mutations, too, and that's ongoing, again, applying the same concept of trying to really use these SBRTs that work really well in the advanced setting, moving them into earlier stages of disease to help us care for more patients. So overall, I think it's really exciting, and I think it's a huge win for the clinical research community.

Dr. Aggarwal: Well, that's wonderful. And I think this certainly advances the field as this is the first targeted therapy approved for patients with early-stage non-small cell lung cancer. I should add that AstraZeneca, the company that makes this drug, has provided institutional research funding to my institution, and I also serve as an advisor to them, but I was not involved personally in the research of this clinical trial.

I'd like to move on but stay within the field of early-stage lung cancer and talk about another study called the KEYNOTE-671 study, and this is important because it really applies the idea of using immunotherapy before and after surgical resection in patients with early-stage lung cancer. Just to give a little bit of background to our listeners, we now have 3 approvals for the use of immunotherapy in patients with early-stage lung cancer. Two of those are in the adjuvant setting, meaning that if a patient undergoes surgical resection or surgery for early-stage lung cancer, they can receive either atezolizumab or pembrolizumab following that surgery, and that has been shown to improve outcomes in terms of reducing the chances of recurrence.

We also have another approval, which is the third approval in early-stage lung cancer, where 3 cycles of chemotherapy and immunotherapy are administered prior to surgery, also called as the neoadjuvant chemo-immunotherapy approach. This drug that has been approved in combination with chemotherapy is nivolumab, and this approval came from a clinical trial called CheckMate 816 that showed both that patients who received this neoadjuvant chemo-immunotherapy approach had a higher proportion of patients who had complete response or pathologic complete response in their tumors at the time of surgery and also showed that the chances of the disease coming back after surgical resection was much lower amongst those that had received this intervention.

The current study, the KEYNOTE-671 study, builds upon this concept and adds both a before-surgery intervention as well as an after-surgery intervention. So what this study did was it enrolled patients with early-stage, stage II to IIIB non-small cell lung cancer, and patients in the intervention arm received 4 cycles of chemotherapy in combination with pembrolizumab, underwent surgery, and then received immunotherapy with pembrolizumab for up to 13 cycles. Patients in the control arm received only chemotherapy prior to surgery and then placebo for up to 13 cycles after. This was a large study with about 786 patients randomized, and what we found was that those patients that received the intervention had a much higher likelihood of remaining disease-free or event-free following surgical resection as well as in the early analysis, an improvement in overall survival with about a 27% reduction in the risk of death. So I do think that this is the first study that shows us that use of both neoadjuvant as well as adjuvant. So sort of this perioperative approach of using immunotherapy before and after surgical resection can actually lead to improved outcomes. This is ultimately what we want for our patients, improvement in overall survival, improvement in cure rates, etc. The study has been silent on the use of radiation therapy, although it has gone into details in terms of the kinds of surgery that was done. Kristin, what are your views about this?

Dr. Higgins: I think postoperative radiation after resection for non-small cell lung cancer has sort of started to fall out of favor because of the Lung ART trial that was published in Europe, a randomized phase III trial that showed no differences in disease-free survival or overall survival. And that's not to say that there aren't more study questions on ways to give it safer and ways to incorporate radiation in with the chemo-IO approach, and there are some novel ways to do that, and we're going to see some data presented at the World Lung Cancer Conference looking at some of those novel approaches. But standardly, when patients receive neoadjuvant chemo-immunotherapy followed by surgery, we typically would not offer radiation. There are instances, though, when patients have positive margins, for example, and in that situation, it's sort of a discussion on a case-by-case basis. But ideally, we're hoping that most of these patients that go to surgery are able to get a complete resection, and that's really the key component of the decision-making for deciding if patients are eligible for this approach.

Dr. Aggarwal: I agree. Melina, any additional thoughts on this trial?

Dr. Marmarelis: I think it's an exciting trial for the reasons that you mentioned. I think it does bring up a number of questions about whether both neoadjuvant and adjuvant immunotherapy are needed. I tend to like the idea of having immunotherapy present when the tumor is present before surgery, so I like kind of having that on board, but I think we still don't know which is more important.

Dr. Aggarwal: So it certainly raises many more questions, which hopefully will be answered in the future. KEYNOTE-671 trial was conducted by Merck that produces the drug Keytruda, or pembrolizumab. We have received institutional research funding for other trials. I was not personally involved in this clinical trial. I do serve as an advisor for Merck. I think we'll bring you more research from the ASCO Annual Meeting. And I'll turn it over to Dr. Marmarelis to discuss some more exciting research.

Dr. Marmarelis: Thanks, Charu. So perhaps it's not surprising that one of the exciting things I picked from ASCO has to do with mesothelioma. And I just want to put into context a little bit about why this trial was important. This is IND227. It was a cooperative group trial done across Canada, France, and Italy, and this was chemotherapy plus or minus pembrolizumab in patients with pleural mesothelioma that did not undergo surgery. So this was their first treatment, and they were not undergoing surgery. And the reason this trial was important is that in the last few years, we had results from CheckMate 743, which was looking at IPI/NIVO, so a combination of immunotherapies versus chemotherapy. And there was an improvement in survival for those that received double immunotherapy, and that improvement was most pronounced in the non-epithelioid population, which is actually a smaller subset of pleural mesotheliomas.

And so as we've seen in the lung when we look at immunotherapy versus chemo, it raises the question of whether combination immunotherapy plus chemotherapy would actually be better for all and, in particular, for all histologies in pleural mesothelioma. So this was looking at that concept. It took the standard chemotherapy, carboplatin-pemetrexed or cisplatin-pemetrexed, and then combined it with one immunotherapy, so slightly less than the combo immunotherapy seen in CheckMate 743, and that was pembrolizumab.

And what they saw was that there was a small overall survival improvement in the group that got pembrolizumab. Again, that was most pronounced in patients in the non-epithelioid group, so those with sarcomatoid or biphasic histology. And this is really a prelude to several other trials that are coming out in mesothelioma, namely the DREAM3R trial, which is looking at chemotherapy plus or minus durvalumab. That control arm also includes IPI/NIVO, so that will be really important to be able to compare those, and then also the BEAT-meso trial, which is looking at chemotherapy-immunotherapy but also with an anti-VEGF agent, bevacizumab. So I think this was an important trial. It's a little bit of proof of concept, but there's still a lot that we're looking forward to. It's not quite practice-changing in the clinic, although I think it's certainly an option that people are using, but I'm looking for more data going forward.

Dr. Aggarwal: It's incredible to see how far we've come in mesothelioma within the last decade. We are introducing immunotherapy. We're introducing novel agents in the first-line setting.

Dr. Marmarelis: The other trial that I was interested in was KEYNOTE-789, which is looking also at patients with EGFR mutations and those that had the original osimertinib as their first-line treatment or another tyrosine kinase inhibitor and then had disease progression on that TKI. And this is an area of huge need. We have patients that do really well on targeted therapies, and then they have disease progression, and we're looking for additional targeted options, but we're also looking for effective chemotherapy options. And one of the questions that has risen from this is whether there's a role for immunotherapy. We know that immunotherapy alone in patients with EGFR mutations is not very effective when you look at a broad population, but in combination with chemotherapy, it's possible that it can add some benefit. So this trial looked at those that had EGFR mutations, had disease progression after a targeted therapy, and then it randomized them to chemotherapy plus or minus pembrolizumab, so chemotherapy plus or minus immunotherapy, and interestingly, it had no difference in the progression-free survival or the overall survival. So the 2 arms were really similar in terms of outcomes. There was also no difference in the overall response rates of the amount that the drug actually shrinks the tumor. So it really doesn't look like immunotherapy is adding much to chemotherapy for these patients. I think we still need to look a little bit closer because there are probably some patients with EGFR mutations that could benefit from immunotherapy, but we're really not very good at identifying those.

One of the questions that comes up in this space is whether to add anti-VEGF treatment in addition to chemotherapy and immunotherapy. So there are some upcoming trials looking at that.

Dr. Aggarwal: I think this was a trial that was actually very important and again, practice-affirming that this idea of continuing chemotherapy without adding immunotherapy, patients are not losing much. In fact, they're not gaining anything by adding immunotherapy as shown in this clinical trial. I think continuing immunotherapy, so continuing osimertinib, may be important in this setting also because we know that osimertinib can cross the blood-brain barrier. It can provide that CNS [central nervous system] protection.

Dr. Marmarelis: Yeah, I think that's a great point that the comparison here is not chemotherapy plus osimertinib. It's chemotherapy alone. So I agree that the control arm is not quite what some of us do. I agree. I do the same as you do. I also just want to mention that the KEYNOTE trial and the previous trial about mesothelioma used pembrolizumab, which is made by Merck. We have received institutional funding, and I've served as an advisor as well as received honorarium from Merck.

Dr. Aggarwal: Melina, those were 2 very important studies and certainly, I think, answer some very relevant questions in clinic in the management of patients with EGFR-mutant lung cancer, for example. And then I think we look forward to more practice-changing data in mesothelioma. Kristin, I would love to hear research from ASCO from you. What caught your interest?

Dr. Higgins: So I have a special interest in small cell lung cancer. And I think there was one important small cell lung cancer trial that I wanted to review with everyone. It was SWOG S1929. And SWOG is the Southwest Oncology Group, and it's a cooperative group that conducts clinical trials in cancer funded by the National Cancer Institute. And this is a randomized phase II trial of atezolizumab and chemotherapy followed by randomization to continuing the maintenance of atezolizumab with a PARP inhibitor. Now, we know from prior data that PARP inhibition is attractive for small cell lung cancer because PARP is expressed frequently in small cell lung cancer, and there is a biomarker called Schlafen-11 that preclinical data and prior data has shown can predict response to PARP inhibition. And this trial was sort of a proof-of-concept trial, a small, randomized phase II trial testing whether or not that Schlafen-11 biomarker could be used to direct therapy. Now, in this trial, there were 309 patients that were registered. They then had to have their tumor samples sent for central testing for the Schlafen-11 expression.

One thing that I think is important to bring up is that in small cell lung cancer, there's this belief that it's really hard to get tissue samples from small cell lung cancer and it's a difficult thing logistically because it's just a lot harder to access these tumors. But interestingly, in this trial, 80% of patients had tumors that were evaluable for the biomarker, and the median time to the test result was only 7 days. So patients were able to get their tumor tested, get it sent out, get results in a rapid manner, and then be randomized based on these results. The primary endpoint for this trial was progression-free survival, and the primary endpoint was met. Progression-free survival was 4.2 months versus 2.8 months.

Now, I think many people will say the magnitude of benefit here is not very much, but it's small cell lung cancer, and we don't have a lot of positive trials in this space, and we also don't have many trials that have used a biomarker to direct therapy. So I think for those reasons, it's really exciting to see these results. It was also conducted within a cooperative group with multiple different sites across the United States, and the fact of the matter is that we can do trials like this in small cell lung cancer patients, and I think it will sort of serve as a precedent for future trial design. Now, the overall survival for the trial is still premature. It didn't look that much different with the PARP inhibitor, but that doesn't mean that, again, things could change with more follow-up. And I really like the approach of this trial design, and I'm excited to see biomarker-driven trials in small cell lung cancer. Charu and Melina, what do you guys think about this study? And what do you think about our small cell lung cancer patients and our ability to conduct future trials like this?

Dr. Aggarwal: I think this is certainly an advance. As you pointed out, Kristin, it shows us that we can conduct trials in the space. I think it offers a lens into the potential of personalized therapy in small cell lung cancer, which has eluded us for a very long time. The standard of small cell lung cancer has not changed significantly for a very long time, so I think this is very exciting and can't wait to see more things come in the future.

Dr. Marmarelis: Yeah, I agree. I think we've always been asking for additional biomarkers, especially in such a difficult disease like small cell. And so this is really exciting to see potential biomarkers and that it was feasible to actually pose that question and study it. So that part's really exciting.

Dr. Higgins: Great. And I should also say I was not involved in the study, and I'm not associated with any of the pharmaceutical companies that were involved in the study for S1929. And the final study that we wanted to talk about was the phase III LUNAR study, and this is sort of a different type of trial in the setting of advanced non-small cell lung cancer. It was studying tumor treatment fields with standard of care in metastatic non-small cell lung cancer after progression with platinum-based therapies.

And first, I just want to step back and explain what tumor treating fields are. Tumor treating fields are applied to a patient with a transducer that's placed on the skin, and what it does is it applies an electrical field, and that disrupts mitosis when the cancer cells are trying to divide. And the mechanism of cell death is a little bit unclear. There are sort of many mechanisms that are postulated, one of which is immunogenic cell death, but we don't really know, I think, what's happening. But there have been studies that show improved results with tumor treating fields and other diseases. For example, particularly in glioblastoma multiforme, tumor treating fields are used in combination with surgery, radiation, and temozolomide (Temodar). So it's something that's being used in other disease sites, and this is some of the early data that we've seen in metastatic non-small cell lung cancer.

And so in this trial, 276 patients were randomized to tumor treating fields plus standard of care or standard of care alone. Now, I should mention that this trial began enrolling patients in 2016, and so the standard of care was very different. After platinum-based therapies, the standard was considered docetaxel. Of course, platinum-based therapy alone for frontline treatment of advanced non-small cell lung cancer is also not the standard of care anymore. And so I think with that in the background, it does make interpretation of these results somewhat difficult, and that's probably the major caveat to this study. But nonetheless, patients were randomized, 276 patients. The primary endpoint of the study was overall survival. They were looking at progression-free survival and overall response rates as secondary endpoints as well as overall survival in patients that received immunotherapy versus just chemotherapy alone. And the trial was positive. Overall survival was improved. The median overall survival was 13.2 months for patients that received tumor treating fields with standard of care versus 9.9 months for standard of care alone. If you look at 3-year survival, it was 18% versus 7%.

I think this is a new type of therapy for our patients with non-small cell lung cancer. It is somewhat of a difficult thing to wear the transducer, and you have to wear it for many, many hours. So that is one thing that I think can be difficult for patients that are using this treatment, but nonetheless, it is something new for advanced non-small cell lung cancer. I do know that the technology of tumor treating fields is being studied in other settings for non-small cell lung cancer, for stage III non-small cell lung cancer, for example, and also in the frontline setting. I think this trial kind of speaks to the fact that the landscape of advanced non-small cell lung cancer is changing so rapidly, and when we're studying something novel, we have to make sure that we make these trials feasible for enrollment so that we can get them completed rapidly, and we can get a readout and it doesn't become obsolete based on this shift in the standard of care. So I think it just really kind of drives home that we need to make sure that we're taking that into account with trial design. It's not standard of care changing right now, but it'll be interesting to see how the data evolves over time. Melina, I'm interested to hear your point of view because I know that these can be used in mesothelioma, maybe not that frequently. What is your experience with tumor treating fields, if any?

Dr. Marmarelis: Tumor treating fields are approved as a device in pleural mesothelioma in the first-line setting in combination with chemotherapy. They have been used off-label in other settings, but that's the device approval. The trial that looked at tumor treating fields in mesothelioma was a single-arm trial, so there was no control arm, and it was really actually just looking at the safety of the device. So I have not used it personally in mesothelioma, although I know of patients and I know of real-world studies looking at its use, and I think it's potentially an interesting modality of treatment, especially in combination with immunotherapy, given that it really doesn't have a lot of additive toxicity. But I think the question is really, which patients are benefiting from it, and which patients are able to actually wear the vest in the case of mesothelioma?

Dr. Higgins: Yeah. Any thoughts, Charu?

Dr. Aggarwal: I agree, and I think this is going to be largely driven by patient experience. I think this is going to be quite onerous to wear this, carry the suitcase, so I would be very interested in patient reported outcomes as well as patient experiences and stories, which will really drive our use here.

Dr. Higgins: Yeah, that's a great point. I should say that this trial was sponsored by Novocure. My institution does have other Novocure studies underway, and we receive research funding, but I was not involved in the study, and I did not personally receive any research funding.

Dr. Aggarwal: Thank you, Kristin. This has been a wonderful review of practice-changing and some promising research that came out of the ASCO Annual Meeting. I hope our listeners enjoyed it, and we'll be sure to update you with the next annual research conference. Thank you, everyone.

ASCO: Thank you, Dr. Aggarwal, Dr. Marmarelis, and Dr. Higgins.

You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

The theme of the 2023 ASCO Annual Meeting was "Partnering With Patients: The Cornerstone of Cancer Care and Research." From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today's episode, our guests will discuss new research in symptom tracking and improving health equity in childhood cancer.

First, Dr. Fay Hlubocky discusses research on new ways of tracking symptoms in order to improve outcomes in people with cancer. Dr. Hlubocky is a licensed clinical health psychologist with an expertise in psychosocial oncology and a health care ethicist at the University of Chicago. She is also the 2023 Cancer.Net Associate Editor for Psychosocial Oncology.

You can view Dr. Hlubocky's disclosures at Cancer.Net.

Dr. Hlubocky: Welcome. I'm very glad that you are able to join us today. My name is Dr. Fay Hlubocky. I am honored to serve as the Cancer.Net Associate Editor for Psychosocial Oncology. I'm a clinical health psychologist specializing in psychosocial oncology at the University of Chicago Medicine. Psychosocial oncology centers on addressing the emotional needs of patients, caregivers, and clinicians from clinical research and educational perspectives. I have no conflicts of interest to report today.

Today, we will discuss research on quality cancer care that was presented at the 2023 ASCO Annual Meeting. The theme for this year's meeting selected by the 2022-2023 ASCO President, Dr. Eric Winer, required all attendees to critically examine how interactions between clinicians and patients have changed over the years. "Partnering with Patients: The Cornerstone of Cancer Care and Research" centered on the need to observe what has been improved, what has worsened, and what can be achieved to make interactions between clinicians and patients better. The extraordinary quality and psychosocial care research presented at this meeting honored and fulfilled Dr. Winer's theme. For example, one session centered on the use of novel informatics technology to carry out research and care in the cancer clinical setting. This session, entitled, "Implementing Innovation Informatics-based Technologies to Improve Care Delivery and Clinical Research," illuminated the current research progress of implementation for emerging information technology innovations in cancer care delivery.

This session was designed to help oncologists and cancer care team to evaluate whether and how to integrate these innovations into their own clinical context. One outstanding research presentation was by Dr. Monika Krzyzanowska from Toronto's Princess Margaret Hospital called, "Implementing ePROs in the Real World Oncology Practice," where she emphasized the importance of not only identifying and monitoring patient-reported outcomes or specific symptom burdens such as pain, fatigue, depression, or anxiety in the clinic, but yet they need to be monitored across the patient's treatment course well into survivorship at different time points, including at home. Therefore, there is a need for a standardized approach of identifying symptoms from patients because as Dr. Krzyzanowska said, patients forget to report even distressing symptoms, and clinicians at times are not always prepared to obtain these symptoms from patients. Historically, in the clinic setting and as patients receive treatment in the chemo suite, we have moved from paper and pencil clinical assessments to the use of robust assessments via electronic medical records systems in both the clinic and subsequently while patients are at home. She reported that more than 10 randomized clinical trials examined the benefits of remote monitoring for patients who undergo mostly systematic therapy with consistent improvements in both symptom control and other outcomes, including survival. She provided very robust real-world and life examples of successful implementation of patient symptom monitoring systems.

For example, these have shown consistently that there's a need of improvements in symptom control, but improvement with the other outcomes. To date, she reported on several ongoing initiatives, including a large oncology community practice in Arkansas, who reported on their preliminary initial experiences with an assessment platform of 1,000 patients on systemic therapy who reported symptoms on a weekly basis. This team identified a very high recruitment rate of 79% with amazing retention rate at 88% at 6 months, dropping to about 67% at 12 months. Another real-world implementation example she noted is the work by the National Cancer Institute-funded SIMPRO consortium project, where 6 cancer centers evaluate symptom burdens in 2 different clinical scenarios: patients receiving systematic therapy and patients recovering from surgery. Here, patient data and symptoms are collected via an EMR-based E-system to readily respond to patient needs. The preliminary data and a whole host of research presentation centered on SIMPRO at the Annual Meeting showed that it was feasible, but yet a dynamic design is needed to address any operational and technical barriers for optimal implementation. Ideal partnerships between oncologists, cancer teams, patients, administrators, as well as the IT team is needed for optimal implementation as Dr. Krzyzanowska emphasized.

Once these interventions are implemented, a study of sustainability of consistent patient reporting with adequate follow-up by team members, such as nursing, is important for long-term practice success. Finally, she reports that the future research of ePROs evaluation will involve novel approaches, such as clinical teams that will need to gather more complex data, including the use of dynamic approaches, such as wearable technologies, machine learning to address barriers and to improve the overall patient experience. In fact, a specific example of this type of research which reported on both the benefits and barriers centering on ePROs trials at the ASCO Annual Meeting included a very large randomized controlled trial by a Danish team led by Dr. Blechingberg Friis to evaluate the effects of remote symptom monitoring of patients with advanced lung cancer completing induction treatment in a Danish setting. Patients were randomized 1-to-1 to a remote symptom monitoring or an intervention arm added to standard care or just a standard care arm alone. Patients in the intervention arm completed an electronic questionnaire from home covering 13 common symptoms related to lung cancer. A severity alarm or threshold was applied to each question where elevated scores were sent to a clinical nurse for intervention. Weekly compliance to symptom monitoring during that first year was 82% with an intention to monitor population.

Although remote monitoring did not significantly improve clinical outcomes for all patients with advanced lung cancer in the Danish population, the benefits were identified for a subgroup of patients not receiving maintenance therapy and for those with a prior organizational experience with ePROs monitoring, which may be essential for improving outcomes of symptom monitoring.

In summary, as indicated by the researchers and Dr. Krzyzanowska, more research is needed using these novel approaches to determine the best ePROs platforms for the practice setting. Yet these approaches are critical to improve the overall quality of life of patients, especially during treatment, after surgery, and well into long-term survivorship. In summary, patients should be encouraged to discuss symptom burdens from physical to emotional with their oncology team and to use this technology.

It was an honor and pleasure to present this research to you today. Thank you for listening to this brief summary of new research and quality care from the 2023 ASCO Annual Meeting. Best wishes.

ASCO: Thank you, Dr. Hlubocky.

Next, Dr. Daniel Mulrooney discusses new research on improving health equity in children, adolescents, and young adults with cancer. Dr. Mulrooney is an Associate Member in the Division of Cancer Survivorship at St. Jude Children's Research Hospital. He is also the 2023 Cancer.Net Associate Editor for Pediatric Cancers.

You can view Dr. Mulrooney's disclosures at Cancer.Net.

Dr. Mulrooney: Hello, my name is Dr. Dan Mulrooney from St. Jude Children's Research Hospital. I am the Deputy Director of the After Completion of Therapy Clinic at St. Jude and primarily care for survivors of pediatric cancers. Like previous meetings, the 2023 ASCO Annual Meeting was quite busy and full of research presentations sharing knowledge and advances in cancer treatment and care. Nearly 100 abstracts were presented concerning children with cancer, and these ranged from early studies of new agents to treat relapsed or refractory cancers, some of the most difficult to cure, to molecular profiling of tumors, to late outcome studies characterizing late effects, improved surveillance methods, and potential preventive treatments for adverse effects after cancer therapy.

Now, while all of these were particularly exciting to hear and learn about, this year's meeting also had an important focus on addressing equitable cancer care for all children diagnosed with cancer. When a child is ill, it affects the entire family and can be very stressful for all concerned and may especially place a burden on families economically, particularly for those who may live in underserved areas or lack resources when their child is first diagnosed with cancer. Importantly, financial stresses can increase over the course of treatment. And unfortunately, studies have shown that outcomes are inferior for children from low socioeconomic backgrounds compared to those from other, more resource-filled backgrounds, despite the same protocol-driven therapies. Today, I'd like to highlight some of these presentations. Please note, I do not have any relationships to disclose related to any of these studies.

A study with the goal of determining the ability to assess social determinants of health in upfront treatment protocols was conducted by the Children's Oncology Group, or COG, a large consortium of pediatric oncology centers that runs national and international trials to advance the treatment of children with cancer. Historically, the COG was only collecting information on race, ethnicity, insurance, and ZIP code. Collecting information on household material hardship may provide information that might be addressed and modified and help improve the treatment of children with cancer. However, before this study, it was not clear if parents would be willing to share this information with their child's treatment team.

Investigators asked parents of children newly diagnosed with neuroblastoma and enrolling on the COG study ANBL1531 to complete a survey about where they live, their household income, and their access to stable food, housing, utilities, and transportation, which were called "measures of household material hardship." Investigators also asked about access to social supports. The surveys were administered with paper and pencil and in the primary language of the participant. 360 of 413 eligible participants, or 87%, opted to complete the survey across 101 different treating sites. 89% of the surveys were completed within 11 days of enrollment. Most participants answered all of the questions. In fact, less than 1% left some questions unanswered.

Importantly, nearly one-third of participants reported having household material hardship, of which 55% reported a single insecurity around food, housing, utilities, or transportation. And 45% reported multiple hardships in these domains. These investigators are planning to extend this work and evaluate associations with cancer outcomes in the hopes of better understanding the mechanisms of these disparities and developing interventions to address these issues in future COG studies. This study raised important issues about what can be done to improve or minimize household material hardship for families of children with cancer.

In a pilot study conducted by the same study group at the Dana-Farber Cancer Institute and in collaboration with the University of Alabama, investigators studied the feasibility of a randomized intervention providing transportation and groceries to low-income pediatric oncology families. To be eligible, participants had to be less than 18 years of age at diagnosis of cancer and living in a household that screened positive for food, housing, utility, and/or transportation insecurity, the measures of household material hardship, and those who would be receiving at least 4 courses of chemotherapy.

Participants were treated at the Dana-Farber Cancer Institute or the University of Alabama between May 2019 and August 2021, and were randomized to receive the intervention called PediCARE, which provided transportation and groceries versus usual care, and this was conducted over a 6-month period. The main outcome was to test the feasibility of the intervention. Would families participate? And the secondary outcome was to assess what proportion of recipients successfully received the intervention and if they found it acceptable. The total of 40 families agreed to participate and be randomized, and none dropped out of the study. All completed surveys at baseline and at the 6-month follow-up period, suggesting that the intervention was feasible, could be successfully delivered, and was acceptable to families.

Now another study from the large Childhood Cancer Survivors Study, or CCSS, assessed the association between the expansion of Medicaid under the Affordable Care Act, or ACA, and Medicaid enrollment among childhood cancer survivors. These investigators linked data from over 13,000 5-year childhood cancer survivors to Medicaid insurance data across the years of 2010 to 2016. Survivors were adults, ages 18 to 64 years old, and all had been diagnosed with cancer prior to age 21 years, between the years of 1970 and 1999. The analyses were adjusted for age, sex, race, ethnicity, income, education, and chronic health conditions. The primary aim for these researchers was to determine any Medicaid enrollment for greater than 1 month in the year. They found that Medicaid enrollment rates increased in states that expanded Medicaid coverage from 17.6% pre-expansion to 24% post-expansion, compared to those states that did not expand pre-expansion and 16.9% post-expansion. Adjusting for other factors, the net enrollment increase was 6.6 percentage points. In the expansion states, the increase was greatest among survivors of leukemia and non-Hodgkin's lymphoma. It was also greater among non-Hispanic Black and Hispanic survivors compared to non-Hispanic White survivors and among those with lower household incomes or a high school degree or less. These investigators now plan to look at associations between Medicaid access and health care utilization and long-term cancer outcomes, such as chronic health conditions and mortality.

And additionally, a small study from Stanford University reported a partnership with a community-based nonprofit organization [Jacob's Heart] to improve cancer center-based follow-up for Latinx adolescent and young adult cancer survivors, or AYA survivors. These investigators conducted interviews in the participants' preferred language, with cancer survivors, their parents, and staff from the community organization. They were able to identify important themes around unmet needs for this population, such as challenges with obtaining health care and understanding which providers to see for which health issues, an oncologist or primary care provider, uncertainty about what questions to ask these providers, difficulty adjusting to life after treatment, and understanding the late effects of cancer on the whole family, economically and mentally. For example, issues with parental job loss, financial strain, or impacts on other siblings in the home. However, these investigators also found supportive themes such as gratitude, strength, and support. Addressing these barriers is important for families and communities to promote follow-up after cancer treatment. This study was particularly unique because of its ability to successfully partner with a community organization to reach out and provide opportunities to improve care for Latinx AYA cancer survivors.

The studies highlighted here and presented at this year's ASCO Annual Meeting focused on identifying barriers to equitable care for all children diagnosed with cancer and has laid the groundwork for future investigations to address these issues for children and families during treatment as well as after treatment and during survivorship. Thank you for listening to this brief summary of some of the exciting and novel research in pediatric oncology presented at the 2023 ASCO Annual Meeting.

ASCO: Thank you, Dr. Mulrooney.

You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

The theme of the 2023 ASCO Annual Meeting was "Partnering With Patients: The Cornerstone of Cancer Care and Research." From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today's episode, our guests will discuss new research in melanoma and health equity.

First, Dr. Katy Tsai discusses new research in melanoma.

Dr. Tsai is a medical oncologist and Assistant Professor of Medicine in the Division of Hematology and Oncology at the University of California, San Francisco. She is also the 2023 Cancer.Net Associate Editor for Melanoma & Skin Cancer.

You can view Dr. Tsai's disclosures at Cancer.Net.

Dr. Tsai: Hello. Welcome to the ASCO Cancer.Net Research Round Up. I'm Katy Tsai, an associate professor of medicine and the clinical medical director of the Melanoma and Skin Cancer Program at the University of California, San Francisco. I'm happy to be here today to discuss research on melanoma and skin cancers presented at the 2023 ASCO Annual Meeting. I do not have any disclosures relevant to the studies to be discussed.

So, it's always exciting to see the latest research presented at ASCO. One theme in particular that I'd like to highlight in this podcast is recent advances in the field of adjuvant therapy. For the listeners who may not be familiar with this terminology, adjuvant therapy refers to drugs given after surgery to try to decrease the risk of cancer recurrence. Specifically, late-breaking abstract 9505 presented updates from KEYNOTE-716, an adjuvant study of pembrolizumab, or pembro, in patients with resected high-risk stage II melanoma. Late-breaking abstract 9503, which I'll also discuss, presented data from KEYNOTE-942, a pivotal study of a personalized cancer vaccine plus pembrolizumab in patients with resected high-risk stage III and stage IV melanoma.

So, let's start with KEYNOTE-716. We've known for some time in our field now that adjuvant pembrolizumab or nivolumab can help decrease the risk of recurrence for patients with resected stage III or IV melanoma. What may not be as well-known, however, is that patients with stage IIB or IIC melanomas, in other words, thicker, ulcerated primary melanomas, even without lymph node spread, actually have a comparable risk of melanoma recurrence compared to patients with early stage III melanomas. KEYNOTE-716 was a large, international phase 3 study that randomized patients with stages IIB and C melanoma to receive either pembro or placebo. The positive results showing improvement in relapse-free survival led to approval of adjuvant pembro in December 2021, but what was presented at ASCO was an update on distant metastasis-free survival. This is obviously an important endpoint for us because ultimately, if someone is going to develop widely metastatic disease, unfortunately, it is a development of these distant metastases that we are concerned about. So what we saw here is that with landmark 36-month follow-up, there was a 41% reduction in the risk of developing distant metastasis in patients who were treated with pembro compared to those who received the placebo. In addition, there was a consistent maintained benefit in relapse-free survival, and importantly, no changes in the side effect profile. These are important data because I believe it is practice-changing in the sense that this is a population of patients who historically might not ever have been referred to medical oncology, maybe just monitored serially with their dermatologists. And this is an option that should be discussed.

Ultimately, the risk versus benefit about whether to pursue a year of therapy versus maybe consider treatment only at the time of recurrence is a very personalized discussion between a patient and their treating oncologist, but it is an option that should definitely be offered. So let's move on to KEYNOTE-942. The novel drug being tested in this trial is very exciting. We're calling it "individualized neoantigen therapy." So this is basically a platform that allows us to develop individualized treatment for someone based on characteristics of their own cancer. This involves taking the actual tumor specimen, genomic sequencing, specifically whole-exome sequencing is performed to try to identify any changes in the DNA. And then through a bioinformatic pipeline, the mutations in the DNA that are thought to be most likely to generate proteins that can be bound within presenting molecules are then identified in the computer program, then synthesized within mRNA. So very similar to the way that COVID vaccines have been made. So this actually becomes the actual drug product. So in this study, patients were randomized to receive either pembrolizumab by itself for a year, which is, as we alluded to earlier, standard adjuvant therapy, but then with the addition of this individualized neoantigen therapy starting with dose 3 and then throughout the rest of the year.

So the recurrence-free survival data were actually presented earlier this year at another major conference, AACR [American Association for Cancer Research], and were highly positive. At ASCO 2023, I think what was most impressive about the presented data is that distant metastasis-free survival, so again, a similar important endpoint that we discussed with the other trial, is that the distant metastasis-free survival here was quite impressively maintained. There was a hazard ratio of .35, meaning really a 65% reduction in the risk of recurrence for patients who received the personalized neoantigen therapy plus pembrolizumab. So this is a huge advantage for distant metastasis-free survival in this particular population of patients. What was even more intriguing is that usually when we combine therapies, we tend to see additive toxicity, more side effects. And what was really exciting about this particular trial is that the additive toxicity really wasn't as much as you would expect for giving 2 immunotherapies at the same time. I'll also highlight that even though these results are really exciting within melanoma, that part of the reason this data is so exciting is that it represents a really promising platform for therapeutic development and application in other tumors besides melanoma.

So this is definitely super exciting. While perhaps not practice-changing in this moment, it's potentially practice-changing. And I look forward to seeing additional data coming in from planned trials using this particular combination in the metastatic setting in addition to the adjuvant setting.

So on the whole, I do think that updates in adjuvant therapy for melanoma were super exciting to see at ASCO 2023. As I mentioned earlier, it's a very large conference. A lot of exciting data being presented. So I do think that other themes to pay attention to as we continue to sort through existing data and look forward to incoming data from forthcoming trials is looking at neoadjuvant therapy. For example, drug given before surgery to try to improve long-term outcomes. For example, at ASCO this year, there was interesting neoadjuvant immunotherapy data presented not for melanoma, but for a different type of skin cancer called squamous cell carcinoma. So that would definitely be another theme to pay attention to in the coming months and years.

Thinking about novel combinations, for example, what's new in immune checkpoint inhibitors, we've been used to for a long time referring only to anti-PD1 antibodies, anti-CTLA4 antibodies. What was interesting to see this year were updates in novel combinations, for example, PD1 antibodies combined with LAG3 antibodies. Antibodies against TIGIT. So I think this will be another exciting space to pay attention to both in the metastatic skin cancer setting and in the adjuvant and neoadjuvant settings.

Thank you for your time and attention. That concludes my research roundup for melanoma and skin cancers. Thank you.

ASCO: Thank you, Dr. Tsai.

Next, Dr. Manali Patel discusses new research in health equity. Dr. Patel is a medical oncologist and Assistant Professor of Medicine at Stanford University. She is also the 2023 Cancer.Net Associate Editor for Health Equity.

You can view Dr. Patel's disclosures at Cancer.Net.

Dr. Patel: Hi, my name is Manali Patel. I'm the Associate Editor for Health Equity for Cancer.Net, and I'm so incredibly excited to present some really amazing work that was presented at our ASCO Annual Meeting this past June in Chicago. Before I start, I do have one disclosure. I will be talking about studies that were presented relating to patient navigation and one study in particular that my group presented looking at community health workers. And so that is a little bit of a disclosure that I would like to address upfront.

And now, just to get right started. I thought what was really interesting was the amount of work this year that was presented on disparities in health equity. As in past years, we actually saw quite an influx, probably more so this year than previously, on studies that looked at differing outcomes, inequities in cancer care delivery, describing disparities in terms of receipt of treatment, so if people were receiving treatment. There tended to be a lot of studies that focused on looking at and describing a lot of these disparities. But what I was really impressed by came out from the pediatric colleagues, individuals who are taking care of younger patients, children who are less than the age of 18, and how many of those particular studies were focused on moving from description to actually intervening and making a difference in health equity. And so I want to highlight a couple.

There was one that was done out of Dana-Farber, and actually, a multi-site group of authors. So lots of authors from all over the place, but Emily Jones was the lead author. And they described and actually evaluated how they could collect, in the context of clinical trials for children, which is called Children's Oncology Group Trial-- how they could collect social determinants of health data, meaning data that evaluates people's income, transportation, where people live, what kind of work they may do, if they have food and housing insecurity. And what they were able to show is that, by embedding a lot of these data points-- they actually made these data points optional for patients when they came into the clinical trial. And they found high feasibility, meaning lots of people that were signing up to do clinical trials for the Children's Oncology Group Trial were able to complete this extra data, which is extremely important and is a remarkable willingness of individuals to participate in providing this data which is important for their treatment.

Along those same lines, Amy Newman from the Children's Hospital of Philadelphia really did a very nice study looking at the feasibility of what they called PediCARE. And it was this intervention that was focused on trying to ensure that people-- again, children less than the age of 18 across 2 different clinics. They evaluated whether PediCARE would help people to receive necessary and important resources as it relates to social and economic needs. And so they screened for food insecurity, for housing insecurity, for people that had difficulties paying for utilities, and transportation security. And then they randomized individuals to either PediCARE or to just usual cancer care. And what they found was that 100% of the people that were randomized to PediCARE successfully received grocery and transportation resources. They felt that it was easier to buy food for their family, and they reported it was easier to get to and from the hospital and that they would be very likely to report and to recommend this intervention to other individuals. And so it really shows how these interventions can move from just describing that housing, food insecurity or problems-- number 1, it starts with the collection of the data, right? What's really important is making sure that we collect this data because we don't currently do that in cancer care. And then number 2, when we actually do collect the data, what are we going to do about it? And it shows that these interventions really do help people to move past their housing and social and economic issues that they may experience into actually receiving care that's important and necessary to improve outcomes.

We did see a lot of data reflecting the importance of health insurance and big policies, what I call Big P, which are these national policies, like the Affordable Care Act. And now we've seen, just year after year and including this year, plethora of studies showing how beneficial the Affordable Care Act has been on reducing disparities and improving cancer outcomes overall.

We also saw other studies, such as one presented by Dr. Gladys Rodriguez from Northwestern, which looked at disparities in the intensity of care at the end of life amongst patients with gastrointestinal cancers. And the team revealed, across almost 20 years of data in California, that patients were receiving higher rates of what would be considered low-quality care. Now, this is lower hospice use, which we know helps to actually improve survival, lower rates of palliative care use, and greater rates of burdensome hospitalizations. And now, why I think this is particularly important is because this study evaluated what we know is a problem, that there is low-quality care amongst patients from particular racial and ethnic populations, such as Black and Hispanic patient populations, that aren't receiving the right care when they're diagnosed. And then what this reveals is that, even at the end of life, they're perhaps still receiving low-quality care.

Another study looked at screening, which I thought was really impressive. It was by Nicole Anne Gay from the UM Sylvester Comprehensive Cancer Center in Miami. And what they evaluated was essentially a quality improvement program to reduce disparities in lung cancer screening. As a lung cancer doctor myself, it's still shocking that fewer than 6% of people that should receive lung cancer screening, meaning a screening test to help us identify and to treat patients with lung cancer-- they aren't receiving lung cancer screening. And so we know that this is a problem overall. They put into place what's called a multi-level, meaning that there were improvements in the electronic health record that they embedded. They also provided patients with navigation, and they also helped clinicians in the primary care clinics obtain information about who should be eligible and which patients should be receiving screening. And what they found was that they were able to move screening rates from 25% improvement completed during the project period from their baseline, which is actually quite impressive.

We also saw an interesting study, and actually, just an interesting evaluation, of childhood leukemia survival on the U.S.-Mexico border. And it was a description of how to implement changes by strengthening care partnerships. And so they evaluated and they described the implementation of this program to achieve what they called sustainable high-quality care for children with leukemia. It was done by Paula Aristizabal and was really in a unique border health setting. It was in partnership between the North American and Mexican institutions. And they used what was called the strengthening model developed by the World Health Organization to evaluate specific domains and to try to improve a sustainable program for children with acute lymphoblastic leukemia at a public referral hospital right on the border region. And I thought that that study was particularly interesting because it shows how to be able to use an approach to improve the staffing of a leukemia service, to implement a sustainable training program as well for other clinicians to learn how to provide leukemia care, and then also to try to improve clinical outcomes and funding for patients to receive medications through local partnerships. I thought it was a really fantastic description of how to begin to do this work that is extremely necessary in low- and middle-income nations but also even on our own U.S.-Mexico border.

There were also a lot of studies that evaluated the importance of social and economic factors. We know that financial toxicity, which is an unfortunate side effect of cancer treatment and cancer care and a cancer diagnosis overall, is associated with worse outcomes. Financial toxicity means the burdens and costs that arise with having a cancer diagnosis. And now we've seen studies that were presented at ASCO this past year by Dr. Khan, who showed that, within 2 years of diagnosis, are at higher risk for dying after adjusting for many social and also clinical factors. And Dr. Hu also presented data looking at the implications of having a lot of medical debt and death. And what both of these studies showed is that medical debt is associated with having perhaps a lower likelihood of surviving. It does make sense for Dr. Hu's study that one would have a lot of medical debt if they also have a lot of other conditions, but it does begin to shed some light on the fact that there are worse clinical outcomes, meaning people aren't doing as well, depending on how much other medical care expenses they may have.

And then finally, one important piece, which I think is really crucial for what's happening now in the way that oncologists may perhaps be able to advocate for payment for services that are important, is looking at navigation studies. Now, this is patient navigators, and that is a very broad topic. And so there were lots and lots of studies that came out at ASCO that evaluated the importance of navigation, including our own work that looked at what happens to veterans after receiving a lay health worker or a navigator to assist with advanced care planning, meaning helping veterans to understand their goals and preferences. And what these studies have shown is that there's actually not only clinical benefit but also, in our own study, that perhaps there may be a survival benefit even 10 years later. It was very wonderful to be at ASCO this past year, and I really hope that you all can look at some of these studies or take away the important and amazing work that's going on in the health equity space. And I thank you for listening to our podcast.

ASCO: Thank you, Dr. Patel.

You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

[music]

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

The theme of the 2023 ASCO Annual Meeting was "Partnering With Patients: The Cornerstone of Cancer Care and Research." From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today's episode, our guests will discuss new research in gynecologic cancers [2:06], multiple myeloma [9:15], and head and neck cancer [16:03].

First, Dr. Lan Coffman discusses new research in ovarian cancer, uterine cancer, and cervical cancer. Dr. Coffman is a physician-scientist and gynecologic oncologist at the Magee-Womens Research Institute and Foundation, and assistant professor in Hematology-Oncology at the University of Pittsburgh School of Medicine. She is also the 2023 Cancer.Net Associate Editor for Gynecologic Cancers.

You can view Dr. Coffman's disclosures at Cancer.Net.

Dr. Coffman: Hi, my name is Lan Coffman. I'm a physician-scientist at the University of Pittsburgh. I'm a medical oncologist that specializes in gynecologic cancers, and I'm happy to discuss research that was presented on gynecologic cancers at the 2023 ASCO Annual Meeting. I do have a relevant disclosure. I participated in one of the trials I'm going to discuss, a trial called MIRASOL. I was the site principal investigator at University of Pittsburgh.

I think there were a lot of interesting studies to highlight, and I wanted to focus on studies involving ovary cancer, endometrial cancer, and cervix cancers as the main sites that we study in the gynecologic oncology world. So when we talk about ovary cancer, I think there was one really impactful study that was presented at ASCO this year, and it was called MIRASOL. And again, this is the study that I also participated in at our hospital at University of Pittsburgh. So it was a large study, so a randomized phase 3 study looking at a drug called mirvetuximab, which is an antibody-drug conjugate.

So basically, it's an antibody against a protein that is expressed on ovarian cancer cells and the protein's called folate receptor-alpha. And that antibody basically carries a little poison. And so it's kind of like a Trojan horse. This antibody goes, finds that protein on the tumor cells, and then delivers that poison. And so this drug has been studied and actually was presented last year in a different trial called SORAYA, which showed that it had activity, meaning the drug helped to kill ovarian cancer cells, and actually led to the first approval of this drug in ovary cancer. So this trial was the confirmatory trial, so enrolling more patients to see, actually, is it better than standard-of-care chemotherapy? So this was in women with ovarian cancer that had come back and was platinum resistant, meaning the cancer started to grow within 6 months from the last platinum-based therapy. Women were eligible if they had high expression of this folate receptor-alpha, and they had to have a couple of prior lines of therapy.

And then they were randomized, so kind of chosen out of a hat to either be treated with mirvetuximab or with investigator's choice chemotherapy. So one of the chemotherapies we'd use standardly. And so that would be something like taxol, or liposomal doxorubicin, or topotecan. And basically, this study was comparing how well does mirvetuximab work compared to chemotherapy. And importantly, it showed that it improved survival, both progression-free survival, so how long it took before the disease started to grow again, but probably more importantly, actually improved overall survival, so how long a woman lived. And actually changed overall survival from about 16 and a half months compared to 12 months with chemotherapy. And so this was really important and demonstrated that mirvetuximab does actually impact women with ovarian cancer and actually helps women live longer. And that's really hard to do in this setting.

And the other nice thing about this trial was that not only did it work well, but there are actually lower side effects with it, and so less women actually had to discontinue their treatment, and they had less what we call adverse events, or basically bad things that had happened from the treatment themselves. So just telling us that this drug is actually well tolerated. Women feel well on it, even when their cancer is shrinking. So I think that was one of the most impactful studies in ovary cancer. Moving on to endometrial cancer. We recently had 2 studies, one called RUBY and one called GY018 that looked at using immunotherapy in combination with chemotherapy in endometrial cancer. And what was presented at ASCO was some follow-up from this RUBY trial, which was basically validating that this combination of adding immunotherapy actually helped. To give you a background, traditionally, women that have endometrial cancer that is advanced staged, meaning spread outside of the uterus itself or has come back, we treat it with chemotherapy.

But this study added an immunotherapy called dostarlimab in combination with our standard chemotherapy and actually showed that women were living longer with this, at least in that progression-free survival. We're still waiting on final evaluation. But at ASCO, what they reported was another independent blinded review of the data to show that even when we're really carefully looking at this data, it looks like immunotherapy helps women with endometrial cancer live longer. They also presented quality-of-life data showing that women actually feel better with the addition of the immunotherapy. So I think this is practice changing. And again, this data has been coming out over the last year or so, but I do think this will change the way in which endometrial cancer is treated.

And then the final thing I wanted to discuss would be in cervix cancer. And while there wasn't a lot of new data presented here in terms of kind of paradigm shifts or large changes, we did have final survival [data] from the KEYNOTE-826 presented, which is also using immunotherapy along with chemotherapy in cervix cancer. And so this was in women that, again, had advanced-stage cervix cancer. So it was a cervix cancer that had moved beyond the cervix itself or cervix cancer that had come back and was treated with chemotherapy along with another immunotherapy called pembrolizumab. And this was the final survival data that confirmed that the immunotherapy did help women live longer. The survival data was impressive with about a 10-month improvement in overall survival. So how long a woman lived. And so that was really confirmatory of the previous trials. So again, that emphasizes that immunotherapy is moved towards the standard of care in cervix cancer as well. I can't hit all the highlights of the impressive research coming out of ASCO 2023, this is a brief summary of some of the critical studies in gynecologic cancers.

ASCO: Thank you, Dr. Coffman.

Next, Dr. Sagar Lonial discusses new research in multiple myeloma. Dr. Lonial is a professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University, where he also serves as Department Chair. He is also the 2023 Cancer.Net Associate Editor for Myeloma.

You can view Dr. Lonial's disclosures at Cancer.Net.

Dr. Lonial: Hello, I'm Dr. Sagar Lonial from the Emory School of Medicine and the Winship Cancer Institute in Atlanta, Georgia. And today I'm going to discuss some of the really exciting research in the context of multiple myeloma that was presented at the 2023 ASCO Annual Meeting. In terms of my conflicts of interest, I have enrolled patients on many CAR T trials as well as bispecific trials from all of the different companies involved here. So, I do have some engagement with those trials. And one of the studies that I may talk about at the end came from our institution. So I was an investigator on that study as well.

When I think about some of the really exciting work that was presented at ASCO this year, there are really 2 big categories of trials that I think were most exciting. And the first is CAR T-cells and moving them earlier and earlier in the disease state. And what we saw at ASCO this year was the CARTITUDE-4 study, which was a randomized phase 3 trial comparing CAR T-cells versus standard treatment in the context of first or second relapsed multiple myeloma. And this was a really important study for us to hear because we know that CAR T-cells are highly effective in the later lines of therapy. A big question at this point is, "Does their efficacy hold up in earlier lines of therapy? And how does it compare in a randomized setting against what we might normally use in that clinical context?"

And what I think we were really excited to see at ASCO this year was that CAR T-cells appear to be superior to standard treatment in the context of that randomized phase 3 trial. Now, there were a few patients who were randomized to CAR T-cells who didn't get to the CAR T-cell infusion because their disease progressed in that interval. And that is a challenge that many of us deal with on a regular basis when we think about using a CAR T in a patient. But in general, the treatment was available for almost all patients. And the analysis of benefit as measured by a longer remission duration for the patients who received CAR T cells versus those who didn't was really done on what we call an intent to treat basis. And what that means is if you were randomized to the CAR T arm, even if you didn't get the CAR T, which again was a very small number of patients, you were still evaluated as if you got a CAR. And what I think that tells us is that even taking into account some of those patients who may not get there, there still was significant clinical benefit.

And this is really important data for us to have insight into. We've seen this with cilta-cel in CARTITUDE-4. We'd seen similar kinds of findings in KarMMa using ide-cel as the CAR T-cell, although it does appear that the remission duration, at least when you're comparing across trials, appears to be a little bit longer for cilta-cel than what we've seen with ide-cel. But nonetheless, it suggests that even in the context of early relapse, there may be some benefit for CARs over standard therapy. Now, does this mean that CARs are going to replace standard therapy in terms of early relapse? I don't think we know the answer to that right now. I think there's a lot of information that we need to look at to really feel comfortable making that step.

The other big set of data I think that we were all very excited about to see at ASCO this year were the T-cell engagers or the bispecifics. And what we saw from a number of different bispecifics was that the efficacy data looks like it continues to hold up. But what to me was really quite exciting was the idea that the T-cell engager could be highly effective even if a patient had seen prior BCMA-directed therapy. And what this means to me is that perhaps if you're progressing on a CAR T-cell, you still may have a pretty reasonable chance at a response, again, to a BCMA-directed therapy with a bispecific. The other way around may not necessarily be the same. And so I think what we learned at this meeting is that the bispecific or T-cell engagers clearly could have activity in the context of prior BCMA-exposed therapy. And I think, as a field, we need to think more about how we define what it means to be resistant to a BCMA-directed therapy. So that I think was really important and exciting and will have relevance in our daily clinical practice.

We also saw updates on a different non-BCMA-directed target. So we saw updates on GPRC5D-targeted bispecifics, also known as talquetamab. What I think was really exciting here is we saw a very high overall response rate, modest infectious complications compared to what we've seen with BCMA-directed therapy.  

Finally, what I want to wrap up with was a very small study addressing what I think is a pretty significant unmet medical need. And that was a trial from Dr. Nooka at my institution, where we evaluated a combination of carfilzomib with pomalidomide and dexamethasone, or KPD. And we used that specifically as maintenance in the high-risk group. And what we learned from that evaluation is that it appears for patients with high-risk disease that KPD maintenance is better than either carfilzomib and len [lenalidomide] or even bortezomib and lenalidomide, which historically has been what we're using.

But there remains an unmet medical need patient population, particularly the double-hit patient population, that even with KPD still didn't have a great outcome overall. So more work for us to do down the road. But certainly, food for thought for many of those other patients that perhaps don't fit into that double-hit classic category. So I think what I've given you is a nice sort of overview of many of the exciting data that were presented at ASCO 2023. Again, go to the website to see additional ones. And thank you again for listening to this brief summary of research in myeloma updates from the 2023 ASCO Annual Meeting.

ASCO: Thank you, Dr. Lonial.

Finally, Dr. Cristina Rodriguez discusses new research in treating head and neck cancer. Dr. Rodriguez is a medical oncologist at Seattle Cancer Care Alliance, an Associate Professor in the Division of Medical Oncology at the University of Washington, and an Associate Member for solid tumor clinical research at the Fred Hutchinson Cancer Research Center. She is also the 2023 Cancer.Net Associate Editor for Head and Neck Cancers.

You can view Dr. Rodriguez's disclosures at Cancer.Net.

Dr. Rodriguez: Hello, my name is Cristina Rodriguez, and today I'm going to discuss some new research focusing on head and neck cancer that was presented at our annual ASCO 2023 meeting. As part of my disclosures, my institution receives research funding from CGEN. My takeaway from this meeting was there were a few major themes represented by the research. One of them was research on uncommon cancer types, such as nasopharyngeal cancer and salivary gland cancer. The other major theme and what was exciting for me was research on groups that were typically not represented in clinical trials in head and neck cancer. These include elderly or frail patients with many other comorbid illnesses that might have excluded them from clinical trials. Another theme was research in areas outside the developed world. In other words, resource-restricted countries. There was some exciting research coming out of that. And finally, a few new agents, novel agents that looked to have activity in patients with head and neck cancer that are going to be studied further.

So with that, I'm going to start with talking about research that came out of France, presented by Dr. Fayette. This was a clinical trial that focused primarily on the frail elderly population. A group that might make very difficult for one to enter clinical trial because of many different illnesses or not being fit enough. And this group, out of France, looked at a combination of immunotherapy and a gentler lower dose chemotherapy called carboplatin and paclitaxel. Interestingly, in this group, there was very encouraging results, including 71% of patients having an objective response or a reduction in the size of their tumor, and very few patients, less than 5% of patients, having toxicity that required permanent discontinuation of the drug. So I thought this study was particularly interesting and gives us physicians and patients who are in this situation some more options to use when we're in the treatment of head and neck cancer.

The next study that I thought was particularly interesting came out of India and was presented by Dr. Kothari. The special thing about this study was that it asked the question of the efficacy of a very low-cost combination for patients with recurrent or metastatic head and neck cancer. It's a combination that we don't tend to use here in the United States, one that involves methotrexate, celecoxib, and erlotinib. This particular clinical trial was carried out in several sites in India, and it randomized patients to this low-cost oral regimen versus physician's choice.

In other words, any type of treatment that might involve immunotherapy or antibody therapy. The main issue here being that sometimes many of these therapies are not easily accessible to patients in low-resourced situations. The investigators observed an overall survival advantage, what that means is more patients lived longer when they use the low-cost oral regimen, which was much more practical, much easier for patients to take, and had more success in improving and prolonging the lives of patients. So I thought that that was a particularly important observation. And we forget a lot of times when we're practicing in the United States that a lot of our practice patterns here may not be applicable to low-resource settings. And I think it's very exciting that research is being carried out to answer questions that are relevant to this area.

The third abstract that I thought was particularly intriguing was one presented by Dr. Glenn Hanna from Dana-Farber. And it looked at a new drug called BCA101. BCA101 is an antibody that has 2 functions. It inhibits EGFR, or epidermal growth factor receptor, very commonly overexpressed in head and neck squamous cell carcinomas. And it has a dual function, which is it modulates TGFβ, which is an immunosuppressive cytokine within tumor cells. This drug was combined with pembrolizumab in this small study and offered to patients who have never received treatment for recurrent or metastatic head and neck cancer. There was a lot of enthusiasm for this drug because in the 33 patients enrolled in the trial, 48% of them had an objective response, meaning a reduction in the size of their tumor. Anemia was one of the more common side effects that were noted. But the efficacy of this agent in this population, these patients expressed PD-L1 or had a CPS score of 1, was enough to support further study of this drug and a larger clinical trial is going to be carried out looking to see if this drug will have similar efficacy or better efficacy in a larger population.

Finally, the last abstract is one that was presented by Dr. Swiecicki. And it was an interesting abstract to me because it examined the activity of another novel agent not FDA-approved for head and neck cancer, called enfortumab vedotin. This is a class of drugs that belong to a group called antibody-drug conjugates. This is an antibody that's directed toward the target called Nectin-4 and has a small chemotherapy payload that's attached to the antibody. Unlike Dr. Hanna's study, this study was a small phase 2 trial that focused on patients who've previously been treated in the recurrent or metastatic setting and are now receiving this drug either as their second or third option after they developed recurrent or metastatic disease. 46 patients were enrolled in this trial, and 24% of patients had an objective response or reduction in the size of this tumor. Although that number doesn't seem very high, it is an encouraging signal because in patients who previously received treatment for head and neck cancer, we tend to see very poor response rates. So this is encouraging given the population that was studied. Another 32% of these patients had what's called stable disease or no significant change in the size of their tumor. So that too is quite encouraging. This drug is going to also move on for further study in head and neck cancer.

So I thought that these themes really brought about a lot of excitement for me for the future of treatments in patients with head and neck cancer, not only in developed countries but also in resource-restricted environments. And I look forward to next year and more work being done in these areas. And I'd like to thank you for listening to this brief summary of developments and head and neck cancer presented in the 2023 ASCO Annual Meeting.

ASCO: Thank you, Dr. Rodriguez.

You can find more research from recent scientific meetings at www.cancer.net.

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The theme of the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting was "Partnering With Patients: The Cornerstone of Cancer Care and Research." From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting, and explain what it means for people with cancer. In today's episode, our guests will discuss new research in breast cancer, lymphoma, multiple myeloma, and brain tumors.

First, Dr. Norah Lynn Henry discusses new research in early stage and metastatic breast cancer. Dr. Henry is Professor and Interim Chief of the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the 2023 Cancer.Net Associate Editor for Breast Cancer.

You can view Dr. Henry's disclosures at Cancer.Net.

Dr. Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of the most exciting new research in breast cancer that was presented at the 2023 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both early-stage and metastatic breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We treat those cancers with anti-estrogen or anti-endocrine treatments, which block estrogen or lower estrogen levels. Other breast cancers are called HER2-positive. These are often more aggressive cancers. But because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or HER2. These are called triple-negative breast cancer and are also often aggressive cancers. Most of the results I'm going to highlight today are treatments for estrogen receptor-positive and HER2-negative breast cancer. One of the main stories from the ASCO Annual Meeting was the result of the NATALEE trial. At the present time, for patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who were at high risk of having their breast cancer come back, the currently recommended treatment is anti-endocrine therapy. Based on the results of a prior trial called monarchE, we also consider adding a medicine called abemaciclib, which turns off some enzymes in the cell that are called CDK4 and CDK6, which are known to make estrogen receptor-positive breast cancer cells grow. Abemaciclib can further reduce the risk of cancer recurrence compared to endocrine therapy alone, but it does have some side effects, most commonly, diarrhea.

In the NATALEE trial, which was presented for the first time at this ASCO meeting, researchers studied a similar type of medication called ribociclib. It acts similarly to abemaciclib, although it is more likely to cause low blood counts and less likely to cause diarrhea. Ribociclib is currently routinely used in combination with anti-endocrine therapy to treat patients with metastatic estrogen receptor-positive breast cancer but is not yet routinely used in the early-stage setting. In the NATALEE trial, patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who are at high risk of breast cancer recurrence were enrolled. Half the patients were treated with just standard anti-endocrine therapy and half also received ribociclib for 3 years. After the 3-year treatment period, those who received both ribociclib and anti-endocrine therapy were about 25% less likely to have their cancer come back compared to those who received only anti-endocrine therapy. Overall, the medication was quite well tolerated. It is important to note that this drug is not yet FDA-approved in the setting.

The remaining trials I will highlight are for treatment of metastatic breast cancer. There were many trials examining how best to use drugs that we are actually already using in the clinic. For example, many presentations were about the CDK4/6 inhibitors that I just mentioned. Typically, patients who have just been diagnosed with estrogen receptor-positive, HER2-negative metastatic breast cancer get treated with anti-endocrine therapy plus a CDK4/6 inhibitor. One trial called SONIA examined whether this is the right approach, or whether patients should just get the anti-endocrine therapy up front and hold off on starting the CDK4/6 inhibitor medication until a later time.

It appears that this delayed approach would reduce symptoms as well as cost of the medication, while not reducing benefit from the treatment. Therefore, it appears it is likely fine for some patients to get just anti-endocrine therapy alone initially. However, we don't know how to identify those patients. Researchers are still figuring out which patients should follow this new treatment plan and which should keep getting the double therapy at the beginning. Some more to come in the future. There was a different trial called PADA-1 that included patients taking anti-endocrine therapy and the CDK4/6 inhibitor, palbociclib, upfront. Those patients were monitored using a blood test, looking for a mutation or a change in the estrogen receptor in the cancer. Patients who had that mutation either remained on the same treatment that they'd been on or switched to the next line of therapy, even though their scans didn't show any progression of their cancer. Overall, this switching strategy looks like a very promising approach for managing patients since it may help patients' cancer respond to treatment for a longer period of time. Although this approach is not yet officially recommended according to our guidelines. In another example, many patients with all types of metastatic breast cancer are treated with a drug called capecitabine, also known as Xeloda. Although this drug is effective for many cancers, many patients experience hand-foot syndrome, nausea, diarrhea, and mouth sores. In the X7-7 clinical trial, the researchers compared the official standard FDA-approved dose based on a patient's height and weight and given for 14 days followed by 7 days off. That was compared to a fixed dose of treatment given 7 days on and 7 days off. The trial found that the fixed-dose regimen was easier to tolerate, but importantly, the benefit from the 2 doses and schedules of treatment appears to be similar.

Therefore, we will likely be using this lower dose, 7 days on and 7 days off, for most of our patients who receive treatment with capecitabine for metastatic breast cancer, since it is likely to improve their quality of life while not negatively impacting the potential benefit they receive from the therapy.

There were a lot of other research findings presented that are related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, including a new antibody-drug conjugate against HER2, as well as other new anti-endocrine and targeted treatments. We eagerly await the results of large, randomized trials so the drugs that work can be used to treat patients with breast cancer. But for now, that's it for this quick summary of important research from the 2023 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you.

ASCO: Thank you, Dr. Henry.

Next, Dr. Christopher Flowers discusses new research in lymphomas and multiple myeloma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and Division Head ad interim of Cancer Medicine. He is also the 2023 Cancer.Net Associate Editor for Lymphoma.

You can view Dr. Flowers' disclosures at Cancer.Net.

Dr. Flowers: Hello. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and interim division head for cancer medicine at the University of Texas MD Anderson. And it's my pleasure to talk to you today in this Cancer.Net podcast about latest updates in the hematological malignancies focused on lymphoid cancers from the American Society of Clinical Oncology Annual Meeting. The ASCO Annual Meeting every year is an exciting time for latest updates in the care of patients with cancer. And in particular this year, there were 3 abstracts that I'd like to highlight that were presentations at this meeting about lymphoid malignancies that have potential significant impact for patients over time. The first 2 come from a special session that was on late-breaking abstracts that were latest advances from clinical trials. The first is from the ZUMA-7 trial. This is a trial looking at axicabtagene ciloleucel, a chimeric antigen receptor T-cell therapy, or CAR T-cell therapy. The CAR T-cell trial in question here was led by Jason Westin, who's a colleague of mine at MD Anderson. And MD Anderson is a partner with Kite pharmaceutical company that is a manufacturer of this and has a research alliance with that group.

In the ZUMA-7 trial, this was a trial that involved the use of CAR T-cell therapy in comparison to standard-of-care therapy, which typically would be aggressive chemoimmunotherapy followed by autologous stem cell transplantation for patients with relapse of large B-cell lymphoma. As many of you may know, large B-cell lymphoma is a kind of lymphoma that is potentially curable with standard frontline therapy. And when patients relapse, the standard of care historically had been for patients to receive autologous stem cell transplantation, which is also potentially a curative therapy. This trial to do a ZUMA-7 trial compared patients who received the typical standard of care, the autologous stem cell transplant following the aggressive chemoimmunotherapy regimen for patients who had relapsed early after their initial therapy, so within 12 months, or were refractory, meaning that they did not respond to their initial therapy. And this was compared to the axicabtagene ciloleucel or axi-cel CAR T-cell therapy. The initial publication of the trial came out in the New England Journal of Medicine in 2022 and showed that the event-free survival for patients who receive CAR T-cell therapy was superior.

This update of the ZUMA-7 trial at the ASCO Annual Meeting that was presented by my colleague, Jason Westin, discussed the overall survival of the study, and in this update, it showed that overall survival was also improved for patients who received axi-cel as opposed to standard-of-care therapy. And now with a median follow-up of a little bit more than 47 months, axi-cel demonstrated superiority that was statistically significant and clinically meaningful over the traditional standard of care.

In that same session, there was another trial looking at CAR T-cell therapy for patients with multiple myeloma. This was a BCMA-targeted CAR T-cell therapy that was presented by Dr. Dhakal in that session providing results from the CARTITUDE-4 global randomized phase 3 clinical trial. That was a trial that involved 419 patients where patients were randomized to cilta-cel CAR T-cell therapy for myeloma or standard-of-care therapy, which in this case included combination therapy. And in this trial, this showed that single agent with a single cell-to-cell infusion significantly improved progression-free survival versus standard of care for patients with multiple myeloma who had 1 to 3 prior lines of therapy and were refractory to lenalidomide. This is also a meaningful advance for patients with this disease.

And the final abstract that I'll mention is an abstract that was presented by Dr. Alex Herrera from City of Hope and was presented in the Plenary session. And it was really exciting to see a Plenary session presentation focusing on lymphomas. So this trial presented by Dr. Herrera was led by the Southwest Oncology Group. Dr. Sara Ahmed from MD Anderson, from my institution, was a participant and actively engaged in this clinical trial. This trial was a success in a number of ways. First, it involved both pediatric and adult patients and is one of the first trials of its kind to involve both large populations of patients with pediatric lymphomas as well as adults with lymphomas. It helps to consolidate the approaches that we use for Hodgkin lymphoma, both in the pediatric population and the adult population. It also represents a major advance in the ways that we conduct clinical trials in the United States in that this clinical trial finished ahead of schedule in terms of completion of the trial with collaboration from the adult and pediatric groups across the National Clinical Trials Network. As I mentioned, this was presented by Dr. Alex Herrera in the Plenary session and involved patients with stage 3, 4 Hodgkin lymphoma, where patients were randomized 1 to 1 either to receive an anti-PD-1 therapy, nivolumab, with chemotherapy, the AVD chemotherapy regimen, or the antibody-drug conjugate, brentuximab vendotin, combined with that same AVD chemotherapy. And what this showed in 994 patients who were enrolled from 2019 to 2022 was that there was a benefit for patients who received the combination of nivolumab AVD or NAVD versus the group that received brentuximab and AVD. It improved the progression-free survival in patients with advanced-stage Hodgkin lymphoma.

In this trial, few immune-related adverse events were observed and a lesser number of patients went on to receive radiation therapy, which is also a benefit for patients with Hodgkin lymphoma. And this concludes my presentation of abstracts at the ASCO Annual Meeting and really exciting advances for patients with lymphoma that were presented this year.

ASCO: Thank you, Dr. Flowers.

Finally, Dr. Roy Strowd discusses new research in treating brain tumors, including those in people with von Hippel Lindau syndrome. Dr. Strowd is a neurologist and neuro-oncologist at Atrium Health Wake Forest Baptist Comprehensive Cancer Center. He is also the 2023 Cancer.Net Associate Editor for Central Nervous System Tumors.

You can view Dr. Strowd's disclosures at Cancer.Net.

Dr. Strowd: Hello, everyone. This is Roy Strowd. I'm a physician neuro-oncologist at Wake Forest University School of Medicine in our comprehensive cancer center. And I'm really excited to be with you for this podcast on important CNS or brain tumor updates from the 2023 ASCO Annual Meeting. I don't have any relevant disclosures for the research that we'll discuss today. It was a really exciting meeting. It was actually a really fun meeting to be a brain tumor doctor at ASCO this year. So I'm really excited to talk with you about some important updates. And I think it's actually a really important time to be a patient and a caregiver and know some of the things going on in brain tumor care. So I'm going to dive into 3 studies. And one that we just have to talk about, and this was a really exciting study called the INDIGO study. At ASCO, if you present a study, you want to have a Plenary presentation, you want to be up on the big stage presenting your work. And brain tumor studies aren't always on the big stage. We just haven't had enough really good treatments out there for brain tumor patients over the years. And this year, we had a Plenary presentation, a really big study, making a big splash. And that was this INDIGO study. So I'm going to spend a few minutes talking about that study. I want brain tumor patients and caregivers to know about this and know about some of the important updates from the Annual Meeting.

The study was called the INDIGO study, and it's a phase 3 study. So when you think about clinical trials, there's a phase 1, phase 2, phase 3. That phase 3 is that last step, that last hurdle that a drug needs to overcome to move towards approval. And a positive phase 3 study is really exciting for the field and means that we may have a new treatment that will change how we take care of brain tumor patients. And that's what this study was. It was also a really unique study. So it's looking at a different group of brain tumor patients, patients that have an IDH mutant glioma. Most common brain tumors that we see are the glioblastomas. And those are often and really, by rule, IDH wild-type. IDH is a gene. It's called the isocitrate dehydrogenase gene. And it's one of these really important genes for us to understand how brain tumors are going to work and how they act and it turns out, with this study, how they may respond to treatment.

So this study looked at enrolling patients that had an IDH-mutant low-grade glioma, or a grade 2 glioma. Those are those often slower-growing, but they continuously grow tumors that occur early in life, typically in the 30s or 40s for young people. And we haven't really had a lot of good treatments for these patients. And so this study looked at giving a new drug that's called vorasidenib. It's hard to say vorasidenib. And it's an IDH mutant inhibitor. So it attacks that IDH mutant gene that makes these tumors what they are. And it's been undergoing development for many years. It's an exciting treatment because it's what we call a molecularly targeted treatment. It specifically targets that IDH gene that makes the low-grade tumors low-grade tumors. This study enrolled 331 patients, so a large group of patients. Half of those patients received the drug, the vorasidenib, and half received placebo. And that's pretty uncommon in cancer. We don't often do studies that are placebo-controlled studies. But for these patients, there's often not a good treatment early in the course, they get surgery. And for patients that don't need an additional treatment, we do surgery and then we wait and watch and see what happens. And that gives us an opportunity as a brain tumor community to figure out whether this type of treatment will help prevent the need for a next treatment, prevent the need for radiation and chemotherapy. And so that's what was looked at in this study. And there was some really exciting data.

So I'm going to go through a few numbers, but we just got to talk about these numbers because they're really important. So at 14 months, 28% of the patients receiving the drug vorasidenib had progressions. That's about a quarter of patients compared to half that received placebo. So that's a big improvement in the number of patients whose tumor grew. So this drug prevented tumor growth in these patients. And that's exactly what we want. That's why we develop drugs, is to prevent tumor growth. When we look at the time that those patients had until they needed a next treatment or until their tumor grew, it was over 2 years of time patients receiving the drug when their tumor grew versus less than a year, 11 months for those receiving placebo. So it's adding a lot of time for brain tumor patients without tumor growth or without needing another treatment. And typically, these patients with low-grade gliomas would need something like radiation therapy or chemotherapy. And those are good treatments, and we need those treatments. But they can have toxicity. And so this is the type of drug that could prevent that toxicity, cognitive decline, other problems that can happen with chemotherapy that those patients didn't potentially suffer.

So there are some important things that we learned from the INDIGO study that I would want you to take away, kind of what do these data mean? The first is that we can target this IDH gene. And that's really important for our field. And it means if you're a brain tumor patient, knowing whether your tumor is IDH mutant or IDH wild-type is important, and that's something I want brain tumor patients to ask me as a neuro-oncologist and ask their cancer doctor because that's important in deciding treatment for them. The second is this medicine vorasidenib, it gets into the brain. And that's one of the big challenges that we have in brain tumor care in developing drugs is we need things that get into the brain. And this study really shows that this is a good medicine. There's a number of IDH inhibitors, but this medicine vorasidenib is one that we want to specifically think about for our patients. And this is a practice-changing study. So for the first time, we now have a treatment that works for grade 2 gliomas and really prevents the need for radiation therapy and chemotherapy. So those are 3 important things to take away from this.

There's a number of things that we don't yet know. This medicine is not available. So patients coming in and emailing me and calling me, we don't have it yet. And after a big phase 3 study like this, this is announced. There's still a number of steps that need to happen to make sure that this can be delivered to patients safely and we can get it out there. And that's in partnership with groups like the FDA, the Food and Drug Administration, and others. So this is an important conversation to have with patients, neuro-oncologists, and to know that this is something that's on the horizon. Two other things is we don't know if this is going to work for all brain tumors. In particular, for these IDH wild-type glioblastomas, the most common brain tumor, this probably is not a good therapy that we don't have any data to suggest that it would work. They don't have that IDH mutation. And so this is important for some brain tumor patients but not for everybody. And that needs to prompt a conversation with the cancer doctor. And it may not work at all times. So there's some data to suggest that this is really a drug that's best given early in the course of treatment and not later on. And so it is something that I want my patients to be aware of at the first time that I see them so we can be deciding what kind of the right time is.

So I want to give folks 2 take-homes from this study and summarize a few of these things that we heard about because it's such an important study. So what are the 2 take-homes from the INDIGO Study? The first that I wrote down is targeting IDH mutation in glioma works. And that's a groundbreaking discovery from this. This is really important for our field. IDH mutations have been important to diagnose brain tumors but have never been really a therapeutic target. And this changes the landscape, and we can now target IDH mutations in gliomas. And that's really important. The second thing, the second real take-home message, is we can safely delay radiation therapy and chemotherapy in some patients with these lower-grade gliomas, potentially with IDH mutation and IDH inhibition. And that's really important. Chemotherapy and radiation therapy are important, but if we can delay those treatments and prevent side effects, that could be helpful for some of our patients. So really important update from ASCO and what I want to spend most of the time on our podcast focusing on this INDIGO study. But there were a bunch of other things going on in brain tumors at ASCO, as there always are. And I want to highlight 2 studies about some things that the groups of patients may be interested in knowing that happened at the meeting.

The first is a study called the INB-200 study. And this is a phase 1 study, so it's earlier in development. But it's an immunotherapy study. And brain tumor patients and caregivers will know that we've really wanted to find an immunotherapy that works for brain tumors. And we haven't yet. And we're still not there, but this study is an important step in that direction. So this study from a group at the University of Alabama looked at something called gamma delta T cells. And T cells are really important. They're part of the anti-tumor response. They're what the body uses to attack the tumor. So we like those T cells. And particularly, these gamma delta T cells are important in targeting tumor cells in glioblastoma cells. They're also unique. They can avoid the toxicity of chemotherapy. Radiation therapy and chemotherapy suppresses the T cells. They make some go down, or decreased in number, which is not what we want. And these gamma delta T cells were genetically created so that they were resistant to chemotherapy. And that's really, really important. We want an immunotherapy that works and one that isn't suppressed by our other treatments. And that's been a real barrier for glioma patients.

So in this phase 1 study, they found the right dose of these gamma delta T cells, and that's the goal of a phase 1 study. But there were some early signs that this may be changing the tumor. One of the patients underwent surgery before and after they got this infusion. And we were able to see this. Investigators were able to see the gamma delta T cells up in the tumor. So this doesn't change practice. Patients don't need to go out and seek out the gamma delta T cells yet. But it's one of those early findings that says that we need to keep looking at immunotherapy. And as a community, this is something we need to keep focusing on.

And then the last abstract and study I wanted to focus on is for a rare disease. This would not be something that would be relevant for all of our listeners and the brain tumor patients but for a subgroup of patients that have a condition called VHL, or von Hippel-Lindau. And von Hippel-Lindau is a genetic condition. So, most brain tumors are not inherited. You don't get it from a mom or a dad or pass it on, except for these patients, you do. And it comes from a gene that's inherited in families called the VHL or the von Hippel-Lindau gene. And these patients are predisposed to get tumors all throughout the body and the kidneys and the brain and the eye. And this is a lifelong disease where these tumors can really grow slowly over time and cause significant problems. And in the past few years, there's been a new treatment called belzutifan. Belzutifan is the name of this drug that has been shown to be effective in the kidney tumors for patients with VHL. And at ASCO this year, there was a new study showing that it's also effective in treating the brain tumors for these patients. And that's really important. We just haven't had a treatment other than surgery or radiation therapy for these tumors. And oftentimes, they grow after surgery and radiation therapy and we need an additional treatment.

So in this study, the investigators looked at, "Does this drug belzutifan work for treating the CNS tumors, hemangioblastoma?" And found that around 50% of patients had a response, so a shrinkage in the size of the tumor. 90% of patients had control of their brain tumor disease, which is really important. And it worked really quickly, so it worked in about 3 to 5 months, which is shorter than what we would see for the kidney tumors. So that's exciting news for VHL patients, patients with von Hippel-Lindau, and another important update from the 2023 ASCO.

So thanks for listening to this update of CNS brain tumors at the 2023 ASCO Annual Meeting. Again, I'm Roy Strowd, a neuro-oncologist at Wake Forest University School of Medicine. Delighted to bring you this brief summary of new research in the field.

ASCO: Thank you, Dr. Strowd.

You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In September 2022, ASCO and the Society for Integrative Oncology, or SIO, published a joint guideline on using integrative therapies to manage pain in people with cancer. Integrative therapies are treatments and techniques used in addition to standard cancer treatment to help people cope with the side effects of cancer, including cancer-related pain.

In this podcast, Dr. Richard Lee talks to the guideline panel co-chair, Dr. Jun Mao, about these guideline recommendations. They discuss why the guideline was created and the different types of integrative therapies included in these recommendations, including acupuncture, reflexology and acupressure, hypnosis, massage, yoga, guided imagery and progressive muscle relaxation, and music therapy.

Dr. Lee is a clinical professor in the Departments of Supportive Care Medicine and Medical Oncology at City of Hope Comprehensive Cancer Center and serves as the medical director of the Integrative Medicine Program. Dr. Lee is also the 2023 Cancer.Net Associate Editor for Palliative Care. Dr. Mao is chief of the Integrative Medicine Service at Memorial Sloan Kettering Cancer Center and holds the Laurance S. Rockefeller Chair in Integrative Medicine at the institution.

View disclosures for Dr. Lee and Dr. Mao at Cancer.Net.

Dr. Lee: My name is Richard Lee. I'm a clinical professor here at City of Hope Cancer Center. I'm in the Departments of Supportive Care Medicine and Medical Oncology and medical director for the Integrative Medicine Program. I'm honored to be accompanied today by Dr. Jun Mao. He's the chief of the Integrative Medicine Service at Memorial Sloan Kettering and holds the Laurance S. Rockefeller Chair in Integrative Medicine. So we're going to talk about the joint SIO-ASCO guidelines that recently came out in the Journal of Clinical Oncology looking at integrative approaches to cancer pain. And so let me first ask you, Jun, could you talk about what is a clinical practice guideline, and how does it help guide cancer care?

Dr. Mao: The clinical practice guideline is a process bringing multidisciplinary experts to look at the evidence from randomized clinical trials or systematic reviews and meta-analysis and to really evaluate the level of the evidence from research and clinical trials, and also incorporate our clinical expertise, consideration for the benefit and risk. Then, making a set of recommendations for doctors and nurses, health care providers to make informed decisions for patients.

Dr. Lee: Great. And tell us more, what is integrative medicine for those patients who may not have a full understanding what this field is about?

Jun Mao: So integrative medicine is a complex term. Originally, a lot of people may have heard that term of "alternative medicine" or "complementary medicine." So those terms are referring to using things like herbs or shamanism instead of a conventional cancer treatment. So recognizing the needs of patients who want to explore alternative ways to help them to cope with cancer, and the importance of adhering to conventional surgery, radiation therapy, chemotherapy. So the field of integrative medicine has emerged. Integrative medicine is a field that is based on evidence and acknowledge the patient's wishes to carefully incorporate evidence-based lifestyle interventions, mind-body treatments, and consider for natural products and herbal medicine in a safe and effective way to improve patients' physical, emotional, and spiritual well-being. Also, part of the goal of integrative medicine is to really engage the patient as an active participant to prevent cancer and to really engage in their own care during and beyond their cancer treatment.

Dr. Lee: And for patients who are new to this concept of integrative medicine or integrative therapies, why is it important for us to study this for cancer care?

Dr. Mao: Richard, this is really important because often when a person gets cancer, you get friends and family who really want to be helpful who say, "Do this, try that, use this herb, or this supplement has been used by that." So there's a lot of anecdote. There's a lot of sort of people just want to be helpful. But in actuality, some of the treatments, without carefully considering actual evidence and potential risks of drug herbal interaction, can induce harm, not only increase the toxicity of the cancer treatment, but may even shorten the lives of cancer patients. Therefore, we often tell patients don't use these treatments as alternative, but to use in an integrated way. And doing research is going to be helpful to understand in what setting for what condition or symptoms. These are helpful, not helpful, are they safe or unsafe?

Dr. Lee: That's really important. That's great to see the research coming along. And so let's talk about ASCO, the American Society for Clinical Oncology, which is the world's leading and largest professional organization for oncologists, as well as Society for Integrative Oncology, SIO. You know, how did they come together to produce this joint guideline on integrative medicine and pain management?

Dr. Mao: So, as you know, ASCO is a world-leading conventional oncology society. It's a multi-discipline, you know, surgeons, medical oncologists, radiation oncologists, a lot of psychosocial supportive care folks are part of this society. Society for Integrative Oncology is a relatively new society, but this year we're celebrating 20th year, so it's not so new anymore. You know, a lot of very passionate physicians, nurses, nutritionists, social workers, we joined together to really help to advocate for evidence-based integrative medicine in the context of care delivery. SIO brings that expertise together with ASCO to formulate a set of guidelines that can be readily implemented into the care setting to help patients and families to deal with pain, a very common and disturbing side effect for cancer and cancer treatment.

Dr. Lee: It's so great to see 2 leading organizations come together to put these guidelines together. So let's jump into the guidelines a little bit, and one of the areas that they covered is acupuncture. So can you let us know and let patients know what is acupuncture, and what types of cancer-related pain has it been shown to be helpful?

Dr. Mao: Acupuncture is a type of therapy that originated from the traditional Chinese medicine. It has been documented over 2,500 years ago. So the way acupuncture works clinically is putting very thin, sterile needles in specific locations of the body to help address symptoms, promote a sense of relaxation and wellness. Often, you need a series between 6 to 10 treatments. I always tell patients it's almost like a physical therapy. You need a few treatments to see the benefit. In animal research, there has been a documented mechanism that acupuncture may help your brain to release endogenous neurotransmitters, like endogenous opiates, serotonin, or dopamine, as a result to reduce pain, increase a sense of relaxation, well-being.

So the ASCO-SIO Joint Clinical Guideline looked at clinical trials, found pretty strong evidence that acupuncture can be used for a type of joint pain that is very common in women with breast cancer taking aromatase inhibitors. Aromatase inhibitors are a class of drug that drop the estrogen level in women with breast cancer as a result of preventing the breast cancer from spreading. Unfortunately, about 50% of women do develop very diffuse joint pain. A lot of time it is in the low back and knees and makes a lot of patients stop this life-saving drug. The committee feels strongly like acupuncture should be recommended as one of the options to treat aromatase inhibitor-related joint pain. In other areas, not as strong, but also in general cancer-related joint pain and musculoskeletal pain. And there are also some weak evidence on acupuncture can be helpful for chemotherapy-induced peripheral neuropathy, as well as to be used in post-surgical related pain. So those are the recommendations we would tell a patient who experienced those pains to try acupuncture.

Dr. Lee: So Jun, you mentioned about the different recommendations around acupuncture, and you're talking a little bit about levels of evidence. Could you explain to patients what you mean by the levels of evidence and the types of recommendations that were put forward by ASCO and SIO?

Dr. Mao: So when experts review evidence from clinical trials, if you have several large clinical trials producing very consistent findings that a therapy is beneficial with very low risk, that will give you a high level, strong quality of evidence with strong recommendation. Unfortunately, in the field of integrative medicine, often there's a lack of funding for this type of research. So what you do see is there are maybe only 1 trial showing that it's very beneficial and maybe there are some smaller trials to show some signal, then we will give an intermediate quality of evidence and moderate strength of recommendation. And then you have therapies that are being used by patients, but there's very little trials or the trials, the sample size are very small. Sample size means how many patients participate. Then you see some promising signals overall, but it's kind of, you know, we don't have a strong confidence in the result. That's where we give low quality of evidence and weak strength of recommendation.

Dr. Lee: That's really helpful and it's, I think, important since integrative medicine is really based on evidence-based approaches that we are looking at the levels of evidence. So thank you for explaining that. Let's move on to some other therapies that were mentioned within the guidelines. You talk about reflexology and acupressure. Can you talk about what these types of therapies are and what have they been shown to help?

Dr. Mao: So reflexology acupressure, so this is a very similar sort of a principle of treatment, but instead of putting needles, it's actually a therapist will put hands on or teach the patient to press specific acupuncture or pressure points as a result to reduce pain or induce relaxation. So here is where you see some intermediate quality of evidence with moderate strength of recommendation for general cancer pain or musculoskeletal pain as the patient is receiving treatment. One common area you would see that is sometimes when a patient's getting chemotherapy, they will have these muscle aches and joint pain. It's not long lasting, but it's very annoying for a number of days. So in those settings, you can try that.

Dr. Lee: So for patients who might have a needle phobia and are very hesitant, would it be reasonable for them to think about reflexology and acupressure as another modality?

Dr. Mao: Oh, absolutely. And also I want to clarify reflexology often is done on the feet. So a lot of patients may not necessarily like general massage. Some people love it, but other people just don't want people to touch their whole body. Then the reflexology just focusing on massaging the feet or lower legs can be a really good option.

Dr. Lee: Yeah, great to see there are options for patients, depending on their preferences. Let's move on to another therapy in the guidelines that mention hypnosis. And so a lot of patients may not be familiar with what is hypnosis and where can that be applied for patients with cancer?

Dr. Mao: Hypnosis is really about changing a state of awareness and a sense of increased relaxation that often allows for improved focus or concentration. But when you talk about hypnosis in a health care setting, it is often done by a provider with verbal repetition, provided with some mental images. Often during hypnosis, patients can be taken to a different mental place and feel a sense of relaxation and calm. And where you see some evidence is actually for procedural pain. This is derived from a large, randomized trial for biopsy, as well as some interventional procedure showing that hypnosis produces benefit for pain reduction, more of acute pain relief. Again, it makes sense physiologically, right? You take your mind and consciousness to a different place rather than focus on the procedure and pain. So this is where we give intermediate quality of evidence and moderate strengths of recommendation.

Dr. Lee: Mm-hmm, good. And let's talk a little bit more about massage. You mentioned that a little bit when you were talking about reflexology. Can you tell us about what situations might massage be helpful for the patients?

Dr. Mao: So massage, many people know is really applying pressure in a specific body area. And certainly, for oncology massage, people need to have some specific training to be safe, make sure people don't put pressure in where the tumor is or where there may be fracture risk for bone metastasis as well as in where their medical port is. So I would advise patients work with people who have specialized oncology training. With that said, I think we find really good evidence, particularly in the area of use in palliative care. So there was a large trial with over 300 people randomized to either massage or just gentle touch. Massage reduced pain and improved mental health. So I would say massage to be utilized in patients living with advanced cancer or for patients in a hospice setting can be a really beneficial tool. Where there is a slightly, sort of a weaker evidence I would say, is in the area of a general musculoskeletal pain as the patient is experiencing treatment or in survivorship. There, we give a low quality of evidence, but a moderate strength of recommendation. The reason we give a moderate strength of evidence is the risk is really minimal, right? Like even though we don't have a good amount of research, but even say massage produces some temporary relief, it can still be very beneficial for the patients.

Dr. Lee: And let's shift gears a little bit to something called yoga, which many of us may know from your local gym. Can you talk a little bit about yoga and what does that mean for patients who have cancer, and how can that help with cancer-related pain?

Dr. Mao: Yoga, as many of you know, originated from India, maybe even as old as 5,000 years ago. So yoga practices, it really combines breath work with meditative work with posture, right, specific postures. So often we know in routine, just health industry, yoga can be really good for physical balance, for flexibility, for induced sense of relaxation. So less is known about the use of that for pain management. So there were some small studies to show that yoga showed really good potential benefit in addressing aromatase inhibitor-related joint pain. The reason we give it a low quality of evidence and weak strength of recommendation is because the research is not as developed in this area. Also, in one of the trials, the pain was the secondary outcome rather than the primary outcome. So it was not the outcome they hypothesized to find, although they did find some benefits. So with that, we do feel like given how yoga is relatively low risk, it's very accessible. So it could be considered for women with breast cancer experiencing aromatase inhibitor-related joint pain.

Dr. Lee: And then, Dr. Mao, could you comment a little bit about--there's so many different styles of yoga. Some of them are very physical, like the kind of hot yoga versus other styles might be more gentle. Can you comment a little bit about that and in terms of what style patients might want to consider?

Dr. Mao: There's also a national organization to help to train yoga instructors to work with cancer survivors. So as you look out for those programs, you should really look at people who have those experiences. And I would say most of the studies use more of a hatha type of, more gentle yoga rather than the probably rigorous sort of yoga. Particularly, I would say for women with breast cancer on hormonal drugs, there's higher risk for osteoporosis. So it's important to consider the risks. And I would work with highly experienced instructors rather than trying very risky moves that potentially can cause musculoskeletal injuries or fractures.

Dr. Lee: Good things to keep in mind as you think about these different therapies. Let's focus more on these kinds of what some consider mind-body techniques: guided imagery, progressive muscle relaxation. Can you talk about these types of therapies, and can the 2 techniques be used in combination to help with cancer pain?

Dr. Mao: So these are very common techniques in the realm of mind-body and relaxation technique. Often you will listen to words and the words will guide you to imagine you're on a beach or hiking in the green meadows. And often there's nice music along with the verbal suggestions. And with progressive muscle relaxation, sometimes we'll ask you to squeeze certain muscle and then release, squeeze and release. By doing that, it also causes a sense of relaxation. So where the application for this is where you see in general cancer pain or musculoskeletal pain. So in those settings, this can definitely be elements to help you improve the coping of pain, it's almost in the realm of self-care. So patients can potentially do that at home. However, I would say the evidence still very low. So the quality of evidence we give is a low quality of evidence and weak strength of recommendation. Although this therapy is very intuitive, they cause relaxation, which should help with pain. But I would say they by themselves may not be... the primary mode to manage pain, but rather than improve the coping of pain.

Dr. Lee: And let's shift gears a little bit to other techniques. One that was mentioned was music therapy. And of course, a lot of people listen to music on the radio or on the way to work. Can you talk about  what is music therapy? Is that the same as just turning on the radio, and where can that be helpful for pain management?

Dr. Mao: So I'm so glad you're asking this question because music therapy is not just music. Music therapy is working with a specialized trained therapist to use music as an avenue to allow patients to develop a very meaningful therapeutic report to induce relaxation, to manage specific physical and emotional symptoms such as pain, depressive symptoms, anxiety. So often, you know, either through playing an instrument, creating sounds, and sometimes by passive listening and passive relaxation. So it's a very sort of an involved process. Where I think there are currently some weak levels of evidence is music therapy for post-operative for surgical pain. That's where there are some research, but because of the trial, the sample size and the control, so unfortunately we can only give a low quality of evidence and weak strength of recommendation. There's much more knowledge about the use of music therapy to reduce anxiety and depression. So, and often those psychological symptoms go hand in hand with a patient with pain. So I do think when we talk about pain management, we shouldn't be so reductionist to just think of a person with pain. Often you have pain, you have anxiety, then you feel depressed about the pain, right? So I think music therapy can play a role to improve the mental coping with pain.

Dr. Lee: I think you bring up a really great point, Dr. Mao, about for patients who are being evaluated for pain to really work with their medical team to explore all the potential factors that might be contributing to the pain. Not only their cancer or the treatment, but their mood or how they're sleeping might play a factor.

Dr. Mao: Rich, as you know, I'm an integrative medicine specialist. So when we work with patients, we really take a comprehensive history to really understand what are the symptoms. Often, I have never seen patients just presenting with one symptom, right? So then you'll understand their symptoms and needs and then help them to prioritize what matters the most for them and which therapies potentially have the biggest bang for the buck to improve the things they want to help the most. And then often those therapies will produce some, what I call the "side benefit," say by improving pain, also improve your sleep, improve your anxiety. So the mechanism may be slightly different, and also patients may have different preference. Some people love yoga, other people would never try it. So you got to really, this is what the beauty is about integrative oncology, to give that choice and control back to the patients. But really, as physicians, we provide them with the evidence to help them to make informed decisions.

Dr. Lee: And what do you think are the kind of key takeaway points a patient should think about based on these guidelines?

Dr. Mao: I think the key takeaway is when you experience pain, don't just think about drugs. Really think about, there are evidence-based non-pharmacological interventions that can really potentially help you reduce pain, improve your emotional and physical coping with the pain. So talk to your doctors and nurses. Are there those therapies available in your cancer center or clinical practice? Or connect you with the qualified community providers and be a strong advocate for your own health.

Dr. Lee: And for patients who really want to dive deep and learn more about these, where would you suggest they go to learn more about integrative therapies for cancer-related pain?

Dr. Mao: Yeah, as a patient as well as a family member, it's really important to go to websites that are credible for reliable information. So, ASCO has Cancer.Net. It provides incredibly valuable information for patients and families impacted by cancer. American Cancer Society will be a good resource as well. National Cancer Institute also have monographs for integrative therapy, so those can be really valuable. Other places like a Society for Integrative Oncology website or Memorial Sloan Kettering Cancer Center website also have a lot of information about integrative therapies.

Dr. Lee: So this has been wonderful. I really want to thank Dr. Mao for a great overview regarding the ASCO-SIO joint guidelines on pain management. And you mentioned a lot of great websites, including Cancer.Net, in which you can learn more about these guidelines as well as other therapies to help with your care.

Dr. Mao: Dr. Lee, thank you so much for doing this really important podcast. I do think as one of the co-chairs for this committee, our group really aspired to use this set of ASCO-SIO clinical guidelines to make integrative therapies part of comprehensive pain management for patients impacted by cancer. And together, we can move closer to allow cancer patients to have lower symptom burden, high quality of life.

Dr. Lee: I really congratulate you and Dr. Bruera for a job well done, co-chairing this really large effort. It took a lot of time. We're looking forward to additional guidelines coming out from ASCO and SIO looking at different symptoms.

ASCO: Thank you, Dr. Lee and Dr. Mao. Learn more about integrative medicine at www.cancer.net/integrative.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Fatigue is a common symptom of cancer and its treatment, and it can be very difficult to treat. However, exercise is one simple method that's been shown to help people with cancer manage and cope with cancer-related fatigue.

In this podcast, Dr. Anna Roshal talks with Dr. Tarah Ballinger and exercise physiologist Danielle Halsey about what people with cancer should know about cancer-related fatigue and the ways that exercise can help.

Dr. Roshal is a medical oncologist and assistant professor of clinical medicine at the Indiana University School of Medicine. She is also a member of the Cancer.Net Editorial Board. Dr. Ballinger is a medical oncologist, an assistant professor of clinical medicine, and the Vera Bradley Foundation Scholar in Breast Cancer Research at the Indiana University School of Medicine. Ms. Halsey is the lead exercise physiologist at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center.

You can view disclosures for Dr. Roshal, Dr. Ballinger, and Ms. Halsey at Cancer.Net.

Dr. Anna Roshal: Hello, my name is Dr. Anna Roshal. I am a medical oncologist at Indiana University, and I am very, very pleased to have 2 great guests today, Dr. Tarah Ballinger and Danielle Halsey, who is an exercise physiologist. And the topic of our podcast today is cancer fatigue. So before we start, I'm just going to disclose that none of us have any relevant conflicts to disclose today.

So I will introduce our guests very briefly. So Dr. Ballinger is also a medical oncologist here at Indiana University. She is an assistant professor of medicine and also an associate director of our supportive oncology program. And like I said, Danielle Halsey is the lead exercise physiologist supporting our Multidisciplinary Oncology Vitality and Exercise (MOVE) program for patients with cancer.

So my first question to start us, and I would direct to Dr. Ballinger, but Danielle, please jump in as well. We all know that cancer patients have a lot of fatigue, and there's many, many reasons why. And it's actually one of the most common, if not the most common concern and complaint that our cancer patients have as they're first diagnosed and as they're going through treatment, and also even after treatment. So it is something that specifically affects their quality of life, maybe more than any other symptoms. So, Dr. Ballinger, can you discuss what are some of the reasons cancer itself and cancer treatments can cause fatigue?

Dr. Tarah Ballinger: Yeah, that's a great and somewhat difficult question. So as you mentioned, cancer-related fatigue is the most prevalent cancer-related symptom, both in patients going through treatment, but even for many years after experiencing cancer. Cancer patients have significantly more fatigue than someone who has not gone through the disease.

The reason why it's so prevalent and so difficult to treat is because the causes of it are so multifactorial. There's, of course, physical symptoms from cancer that can cause fatigue, pain, shortness of breath, depending on where the cancer might be located. And there are psychological symptoms associated with cancer that can cause fatigue, like anxiety, depression.

Definitely trouble sleeping is a big issue. But even beyond these symptoms from cancer, tumors themselves have direct effects that can cause fatigue. So cancer itself causes inflammation that can impact hormone production and other balances in the body that can certainly cause fatigue.

And all of that is before we even start to talk about the other thing you mentioned, which is side effects of treatment. So that includes anemia, which means there's less red blood cells, so there's less oxygen delivery to tissues, and that can make people feel a lot more tired. We also have a lot of evidence that cancer treatments actually impact muscle function at the cellular level. Often what I hear from patients is that they feel sore, like they've worked out, but they haven't actually done anything. And that's really a real thing directly caused by cancer and its treatments. So again, the reason this is so hard to treat is because there are so many potential things that are kind of coming together to cause the problem.

Dr. Anna Roshal: Yeah, that's certainly very interesting. And again, it's complex and lots and lots of factors contributing. I'm curious to hear how would you distinguish, we've all been tired, right? So there's regular tiredness and there is this relentless cancer fatigue that our patients experience. And it's, how do we tell the difference and how do our patients tell the difference? That's most important. How do your loved ones tell the difference of somebody just having a difficult day and they're tired, or is this cancer fatigue that we're talking about?

Dr. Tarah Ballinger: Yeah, cancer-related fatigue is different from the fatigue I might have if I stayed up late or was in clinic all day. That fatigue you can push through and probably will get better if you take a nap. Cancer-related fatigue, classically, it somewhat feels like moving through sand, like you just can't get through it.

Taking a nap tends to not be something that actually makes it better. And I think that can be a real struggle for patients in terms of their loved ones relating to them because a lot of people will think, oh, well just get some rest and you'll feel better. But that's not really how it works for cancer-related fatigue, which is why we try to look for other ways to try to improve this symptom.

Dr. Anna Roshal: That's a great point. I certainly noticed that in my patients and certainly noticed it in my interactions with the loved ones of patients because that's one of the most common responses. So they just didn't get enough sleep or maybe they didn't drink enough water or anything like that. But we do know that it's much more complex than that. So maybe this is a good jumping point to talk about what kind of research has been done to look into how we can make this better.

You know, since fatigue is this very complex symptom affecting our patients' quality of life, what can we do to make this better?

Dr. Tarah Ballinger: Yeah, so that's one of the reasons I'm really excited that we're talking about this prevalent symptom today because one of the, or the best thing that we have found to help with cancer-related fatigue is actually exercise. And that can seem a little bit counterintuitive if you're fatigued that you should exercise, but even light movement can help. So what's really awesome about exercise is that it can target all of those different mechanisms for cancer-related fatigue that I mentioned. And that's really different from what we typically think of in treatment, which is medications. Medications have kind of 1 mechanism of action. They might treat 1 cause of something, but exercise is able to actually treat all those different potential causes of cancer-related fatigue.

So it can help with physical symptoms from the cancer, the psychological symptoms from the cancer, and even those direct effects of the tumor and the treatment. So exercise, it's really one of the only things that's been proven to improve the symptoms of cancer-related fatigue. It helps with our muscle function. It helps improve oxygen delivery to tissues.

And when you exercise, it actually changes your body's immune system and it's anti-inflammatory. So there are true scientific mechanistic reasons for why exercise can be helpful. And again, it's one of the only things that we've proven over and over again can and does improve these symptoms.

Dr. Anna Roshal: That's great. And that's, yeah, like you said, it does seem counterintuitive. And I find that as an oncologist discussing this with patients in the clinic can be quite challenging. Because like, yeah, I'm tired. And you really want me to do what? So yeah. So maybe this would be a great point for Danielle to jump in and talk about what kind of exercise, right? Because when we talk exercise, there are so many different ways people can exercise and do exercise.

So what kind of exercise? Is this walking? Is this weights? And can we talk about, maybe in detail, of what kind of exercise has been looked at and found beneficial or what you recommend for patients?

Danielle Halsey: Yeah, of course. So exercise walking and resistance training have both been proven in lots of research that it is beneficial to patients and their cancer-related fatigue, but also in combination. And one of the big things that I talked to you about with patients is just finding the exercise that works best for them and something that they're going to stick to. And so the actual "dosage," and I say that with air quotes as I say it, but what the research has shown or what strong evidence has shown is that at least 3 times a week of some sort of aerobic activity, so that can be swimming, walking, if you like running, running, if it's biking, some sort of aerobic activity at a moderate intensity that will get your heart rate up for 30 minutes, has been linked to a decrease in cancer-related fatigue.

And then at least 2 days a week of resistance training for at least 2 sets at 12 to 15 reps is going to have a positive impact on cancer-related fatigue as well.

Dr. Anna Roshal: So speaking of types of exercise, you have mentioned walking and resistance training, and even swimming. Are there any other exercises? I know a lot of people like to do yoga or Pilates, especially before, and that's a different form of exercise than maybe going for a walk. What are the patients or people enjoy this more? Is there data for doing more of that type of exercise rather than traditional, let's go for a walk?

Dr. Tarah Ballinger: Yeah, there is data that exists for some of these other forms of movement to improve cancer-related fatigue. So we do have evidence that yoga can help with cancer-related fatigue. Even massage therapy can help with cancer-related fatigue. Tai Chi, we have data for that as well. So I think those are important adjuncts. I think whether or not they can replace traditional aerobic exercise depends a little bit on how you're doing it. For a lot of the benefits of aerobic exercise, like Danielle mentioned, it's just about increasing your heart rate a bit or increasing your breathing a bit. So for some patients, that's happening when they're doing something like yoga, but for others it's not.

So I still think that while those things can be important adjuncts and they can help with a whole comprehensive plan to treat cancer-related fatigue, I think traditional forms of aerobic exercise are still important and getting your heart rate up is important. However, things like yoga, they're still resistance exercise depending on how you're doing them because you are loading parts of your body with your body weight. So there are muscular benefits to doing that as well. So it's all, again, it's all an individualized thing depending on how people are doing it, what they like to do, what they're able to achieve in each of those exercises.

Dr. Anna Roshal: So anything that they can do, but definitely having that emphasis on increasing the heart rate and using your muscles, regardless what that is. Yeah.

Dr. Tarah Ballinger: Yep, exactly. Exactly. And that's really the difference. A lot of times people, we debate as exercise oncology researchers and a lot of people debate the difference between the term "physical activity" and the term "exercise." So both of them are important in different ways. So physical activity is really any type of movement. So if I walk from my office to clinic, I'm doing physical activity.

But I'm not doing exercise because exercise is done with a specific purpose to achieve a specific goal. So to really be exercising, I have to go out for a walk and say, "I'm gonna do this for 5 minutes because I know it's gonna make my cancer-related fatigue better." Then that becomes exercise. So that's an important nuance and a different way to think about it, again, more like a prescription, a medication, something you're doing for a specific purpose.

Danielle Halsey: Yeah, adding that intention where like going for a walk is, you know, a very important thing and being more active throughout the day and getting up and getting steps and things like that, it's going to benefit you. It's going to be a good thing. But adding intentional movement with a goal in mind of that 5-minute walk that is a challenging 5-minute walk versus the 5-minute walk with your, you know, dog who's stopping and sniffing every 2 minutes is going to have a different impact than the exercise that is intentional to get that heart rate up and you're like, speed walking to the stop sign and speed walking back to your door and, you know, little things like that where it's just intentional movement.

Dr. Anna Roshal: Got you. And are there any guides for patients for the information that you just mentioned? Where can they go to find this?

Danielle Halsey: Yeah, there's some really good resources using the American College of Sports Medicine, both their website and finding a health care provider that can get them more information as well. There's actually, on their website, a search bar to find different exercise physiologists or cancer exercise programs like myself that are in your area.

Dr. Tarah Ballinger: I agree. The American College of Sports Medicine probably has the most good resources available online for patients. They have a program called Exercise is Medicine, which is perfect in terms of what I was explaining for how exercise can actually work like a medicine to help with cancer-related fatigue. If you just Google "Exercise is Medicine from the American College of Sports Medicine," you'll find it. And then they have a search area where you can look for professionals like Danielle that might be in your area. There are a couple of other national programs. The YMCAs have a program called Livestrong. Most all of them carry that program, and they have trainers that will work with cancer survivors at any point in their disease journey.

I also work with another program called Maple Tree Alliance. If you Google that resource as well, they have several cancer exercise programs across the country. They also have some exercise videos available online. But like Danielle said, I think the first thing to do is advocate for this resource for yourself and ask your oncology care team about where you might be able to get help with this type of thing. Oftentimes, I think patients can get a little frustrated because they need the type of specific information that someone like Danielle can provide rather than just, oh, you should move around, or you should do aerobic exercise. A lot of patients need to know, how long can I do this? How long should I be doing it? How high should my heart rate be getting? And a lot of those more specific questions need to be answered by a specialist.

Dr. Anna Roshal: Yeah, that's definitely true. And that's, yeah, like you mentioned, it's difficult maybe for just oncology professionals in the clinic to know all of this and have time to consult patients on this. So maybe, Danielle, I know we mentioned a few times that you're an exercise physiologist, but can you explain what you do on a regular basis and who is the exercise physiologist? How is it different maybe from a trainer at the gym? Which is maybe more patients are maybe associating that, but I know that's not what you do.

Danielle Halsey: Yes, yes. It's very funny because when I want to tell people what I do, like random people I meet on the street, I say, "I'm an exercise physiologist." I do put it in layman terms. I say, "I'm a very fancy, well-educated personal trainer some days." But you're not totally off. But generally, what it is, is exercise physiologists are individuals that are highly trained, I have a background in chronic diseases. I have a background in physiology. I have a background in chemistry and all of the similar education as a physical therapist might have had, but my education stopped at a master's comparative to physical therapists who go into a DPT school. And they are more focused on injury where exercise physiologists are going to be more focused on chronic illness and patients who have chronic illnesses. Or, where we typically see exercise physiologists working in health care systems is in cardiovascular departments. My job on the day to day is utilizing the structure of cardiac rehab to develop a cancer rehabilitation program here at IU.

And we've seen how beneficial that exercise can be in the cardiac population. And we've also seen how beneficial exercise can be in cancer rehabilitation, but it's not as well known or established. And so my day to day can vary dependent upon the number of patients that I have coming in, but in an ideal day, I'll see 4 to 5 patients individually. I help them with aerobic endurance. So, we do have a target heart rate and duration on a treadmill or a bike if they prefer one or the other. And then we do about 20 to 30 minutes of resistance training based off of where their baseline is and their overall comorbidities and range of motion and things like that. I spend time in clinic also talking to patients about different exercise modalities that might be beneficial for them, doing a little bit of health coaching, I guess you could say, in the sense of talking to them about what they're currently doing, what they might be able to add to their day-to-day activities, and what would help them maintain their physical activity if they're doing that outside of our program. And then I do assessments with all of our patients as well to just see where their baseline physical function is.

And we use that as the means to build them an exercise program and an exercise prescription to make sure we get them either maintaining their physical function throughout treatment or improving and exceeding their goals, I guess you could say, in the stages after treatment.

Dr. Tarah Ballinger: Ideally, we want to be identifying patients and working with them from the time of diagnosis. So we think of it more like prehabilitation rather than rehabilitation, because if you're able to integrate physical activity and exercise as part of your cancer treatment from the very beginning, we know there are so many benefits to that, not just in terms of your fatigue and quality of life, but also a lot of other cancer outcomes in terms of responding to treatment. So it's really important, but I think the onus is on us as the health care team to help be able to deliver those services directly to patients. And again, we want to do this in a way that is almost like a prescription, very individualized. Like Danielle mentioned, there are guidelines for 30 minutes, 3 times a week, resistance exercise, this many reps of this many things. But for a lot of patients, that might be something they can't do. So your prescription, maybe 5 minutes of walking is enough to get your heart rate up. So you're just doing that every day. Next week, maybe a couple of the days, you can increase to 7 minutes or 10 minutes. So for every single patient, it's different, and we need to provide that support so patients know what to do and have a prescription to follow.

Dr. Anna Roshal: Great description. And then hopefully those services will be available, are available to more of the patients around the country and around the world. Can you speak to other certain types of patients that in your experience benefit more from this exercise-based prehabilitation and rehabilitation? Or is that really all cancer patients?

Dr. Tarah Ballinger: Yeah, so like most things, most of the evidence that exists for the support of exercise and cancer-related fatigue exists in breast cancer, but that's primarily because breast cancer is so prevalent. So it's more well-studied in breast cancer. There's good evidence for exercise preventing or treating cancer-related fatigue when it's done during chemotherapy, when it's done after chemotherapy. But also there's a lot of evidence in patients with lung cancer who have unique reasons for cancer-related fatigue, especially with all of the respiratory symptoms that those patients can have. But I think ultimately, the patients who benefit are the patients who do it. So the patients, yeah, the patients who do it benefit.

What we find the barrier is, is just getting patients through the door in the first place and getting them over that hurdle of understanding the importance of this, not being afraid to do it and kind of trying to find a reason to make this a part of their treatment plan. I always encourage people, again, I sound like a broken record, but I think thinking of this as a medication or a prescription is really important because it should just be a habitual part of what you're doing as part of your treatment. I think cancer patients and people in general wait for some type of magical motivation to exercise. And people always say, "I'm not motivated today. I can't find the motivation." But if you think about it as just something that you need to do every day, like brushing your teeth and taking your medicines, and just get out and go for your walk and try to reframe it a little bit differently, that can be very helpful and very important.

Dr. Anna Roshal: That's great advice. I was thinking about this, making this part of routine, not just in cancer patients, but in all of us. For some reason, the image of the pill box, like many of our older patients use, came to mind. So your morning pills, your evening pills, and there is a box, go out for a walk. Something like that. We need to design that.

Dr. Tarah Ballinger: Yes.

Danielle Halsey: Yeah, I would say that's a big thing. Like in the general population, it's this, a lot of the barriers that general population have to exercise, you'll see the same exact thing with cancer patients. And they're just, they just might be exacerbated a little bit more by this fatigue and the amount of appointments they have and other aspects of their life adding on to, oh, this is one other thing I have to do.

And it is extremely interesting to see the differences in some of my patients who have been active prior to treatment and their diagnosis compared to those who were not active before. And I have 1 patient in particular who was not active before her treatment and any other patient that she's met who was active before her or who was active before their diagnosis, I hear her say, "I wish I had been active sooner. I wish I had been active prior to being diagnosed because I think it would have made a world of a difference in coming back." And so I love the idea of making it a habitual thing. I like the idea of making physical activity something that isn't necessarily like a, "I have to do it" kind of thing, but something I get to do because I need to do it or it's something that's going to help me in the long run as well. And it's something that all of us, no matter our disease status, could benefit from making more of a habitual thing and an everyday task.

Dr. Anna Roshal: Thank you, both of you. I know we talked mostly about exercise as a prescription for cancer fatigue. And I know in the beginning, Dr. Ballinger, you mentioned that really that's the only proven way to really reduce cancer fatigue. Are there any other things that our patients can do to try to cope with the fatigue in addition to the exercise? Obviously not instead, but in addition, are there any other tips that you have?

Dr. Tarah Ballinger: Yeah, so like I mentioned, there are a lot of causes of cancer-related fatigue. So I think thinking about some of those other causes. So mental health is a huge one. So if depression or anxiety are something that you're experiencing, then treating that is going to make your cancer-related fatigue improve. So I always encourage talking to a therapist, a psychologist, if you want to consider taking a medication to help with depression or anxiety, all of those things can help. Sleep hygiene is really important. So again, thinking back to the naps, I encourage people to go for a short walk when they're tired as opposed to taking a nap so that it doesn't disrupt their nighttime sleep quite as much. Better sleep hygiene can help a lot with cancer-related fatigue. We mentioned other things like yoga, acupuncture, massage therapy. For some patients, there are stimulant medications that can help with severe cancer-related fatigue. I've certainly had some patients with debilitating cancer-related fatigue who have benefited from those as additional parts of their treatment. And that brings up the point that I think if the cancer-related fatigue is really severe, then it's definitely something that you need to discuss with your oncologist. You might need other blood work to make sure there's not something else causing you to be very fatigued. Or even sometimes we have to adjust the doses of a patient's medication so that they can better tolerate the treatment if the treatment is causing a lot of the cancer-related fatigue. So I think, again, this is a very complicated, difficult symptom, but there are a lot of ways to address it from multiple aspects that can make things better for patients.

Dr. Anna Roshal: I think that's a very important point, right? Because there could be other reasons besides what we talked about, just the cancer diagnosis and its physiological effects. So I definitely agree with the comprehensive evaluation by the patient's oncologist who then can determine how it was really causing the fatigue and make the appropriate determination for other things, maybe in addition to exercise.

Well, I think this has been very wonderful and extremely informative. I learned a lot. Are there any other things that, Dr. Ballinger or Danielle, you guys want to add for listeners?

Dr. Tarah Ballinger: I think this is really important, and would encourage everyone to empower themselves and believe that they can and should be doing exercise and every little bit counts.

Dr. Anna Roshal: Well, thank you very much, both of you. That's been wonderful. Thank you.

Danielle Halsey: Thank you.

Dr. Tarah Ballinger: Thank you.

ASCO: Thank you, Dr. Roshal, Dr. Ballinger, and Ms. Halsey. You can learn more about exercise during cancer on the Cancer.Net Blog.

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Brielle Collins: Hi everyone, I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. June 15th to June 21st, 2023, marks the third annual National Black Family Cancer Awareness Week, an initiative led by the U.S. Food and Drug Administration's, or FDA's, Oncology Center of Excellence to increase cancer awareness within the Black community. Today we're going to be talking about cancer disparities in the Black community, the importance of cancer screening and prevention for Black families, and resources available to Black families for support. Our guests today are Dr. Luckson Mathieu and Rea Blakey.

Dr. Mathieu is a thoracic oncologist at the FDA in the Division of Oncology 2. Thanks for joining us today, Dr. Mathieu.

Dr. Luckson Mathieu: Happy to be here. Thank you for inviting me.

Brielle Collins: Ms. Blakey is the Associate Director for External Outreach and Engagement at the Oncology Center of Excellence and leads the National Black Family Cancer Awareness Initiative for the Oncology Center of Excellence Project Community. Thanks for joining us today, Ms. Blakey.

Rea Blakey: Thank you, happy to be here.

Brielle Collins: Before we begin, we should mention that Dr. Mathieu and Ms. Blakey do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to begin, Dr. Mathieu, research has shown that Black people are more adversely affected by cancer than other racial and ethnic groups in the U.S. Can you describe some of the cancer disparities that exist in the Black community?

Luckson Mathieu: Sure, thank you for that question. Before providing a description, I would like to first define cancer health disparities. The National Cancer Institute, or the NCI, defines cancer health disparities as adverse differences that exist among certain population groups and cancer measures, such as numbers of cases, the number of deaths, cancer-related health complications, and quality of life after cancer treatment. Black and African American people have higher rates of acquiring and dying from cancer compared to members of other races. For many of the most common types of cancer, including breast, lung, prostate, and colorectal, the incidence and deaths are higher among African Americans than any other racial and ethnic groups. Furthermore, despite having similar rates of breast cancer, African American women are more likely than White women to die of this disease. African American men have a prostate cancer death rate more than double than that of men of other racial groups. Unfortunately, my description is a brief depiction of an alarming and expansive reality.

Brielle Collins: Thank you for walking through that, Dr. Mathieu. And thank you, too, for providing that definition of disparities. And Ms. Blakey, can you describe the purpose of National Black Family Cancer Awareness Week and its role in addressing these disparities and raising cancer awareness in the Black community?

Rea Blakey: Sure, happy to. The purpose of the National Black Family Cancer Awareness initiative and the dedicated social media week is to increase cancer awareness in one of the most vulnerable segments of the U.S. population, as you just heard described. OCE's Project Community appreciates ASCO's Cancer.Net involvement, absolutely. We also aim to marshal community-based stakeholders, faith-based organizations, historically Black colleges and universities, Black sororities and fraternities, all of this to increase cancer awareness and to build knowledge surrounding cancer clinical trial participation, as well as minority population donations to national genetic databases for cancer research. So OCE's Project Community is the hub of the social media campaign for the National Black Family Cancer Awareness Week via our hashtag, #BlackFamCan. Project Community's intent is to enlist and encourage a wide array of public and private community-focused engagement entities, organizations, families even, throughout the U.S. and beyond, to support efforts to increase cancer clinical trial awareness. So with a common and concerted mission, organizers are urged to focus their supportive endeavors and activities to occur during National Black Family Cancer Awareness Week. That's also in conjunction with the White House Cancer Moonshot Goals.

Brielle Collins: Wonderful, and it sounds like that hashtag, #BlackFamCan, is a good place for people to go if they want to learn more as the week progresses.

Rea Blakey: Absolutely.

Brielle Collins: Wonderful. And Ms. Blakey, what do you think is most important for Black families to know about their cancer risk?

Rea Blakey: The hashtag, #BlackFamCan, and there's also a tagline that's called "Engaging the Generations." So we know African Americans have the highest mortality rate of any racial and ethnic groups for all cancers combined and for most major cancers. That contributes to a lower life expectancy, obviously, for African American men and women. And so with that, the real effort here is to get people to talk to their families. All too often, families don't really know their own cancer history, and some find it just too difficult to talk about, especially with older generations who may have associated a stigma with a cancer diagnosis, or those who just don't tell to avoid being perceived as a burden to others in their family. So engaging the generations is one of the key aspects of personal or familial cancer awareness and understanding risk and mapping out preventive strategies and pursuing cancer screening. Not only does it take a village, but it requires every generation.

Brielle Collins: Absolutely. And I want to build on that piece of cancer screening. So Dr. Mathieu, can you talk a little bit about why cancer screening is so important and some of the hurdles that Black families may face in getting regular screening?

Luckson Mathieu: Yeah, absolutely. So cancer screening tests, such as Pap smears, mammogram, low-dose CT scans, and colonoscopy, can help find cancer at an early stage before symptoms appear. When abnormal tissue and cancer is found early, it may be the best time or the more easier time to treat. And treatment may even result in cure. By the time symptoms appear, cancers may have grown and spread, thereby making it more challenging to treat and/or cure. Black people are at the highest risk for cancer deaths. This increased mortality risk may reflect a later stage disease at the time of diagnosis among Black patients. Cancer screening is so important for everyone, especially Black people, because it helps identify cancer early and thereby allows for better clinical outcomes. Regarding the hurdles for cancer screening, I believe the hurdles varies for each family. There may be many complex and interrelated factors that can stand in the way of screening for Black families. Each family should directly address that question of what is in the way of getting appropriate screening for cancer. Identifying and overcoming the hurdles may be the best way to address this cancer screening disparity.

Brielle Collins: Got it. Thank you for walking through that. And in terms of resources, Dr. Mathieu, what resources are available to help Black people access this screening?

Luckson Mathieu: So your primary care physician can serve as a good start to discover cancer screening resources. Earlier this year, the Department of Health and Human Services announced the Accelerating Cancer Screening Program. The program's goal is to accelerate access to cancer screening as part of the Cancer Moonshot Initiative. I would encourage everyone to go online and consider the role a local HRSA-supported health center can play in the process of getting screened for cancer. In addition, NCCN.org, CDC.gov, American Cancer Society, and the FDA are great online resources to obtain more information on cancer screening.

Brielle Collins: Perfect. And I really want to talk about that cancer prevention piece, too, which is another incredibly important element of this. So why is cancer prevention in particular so important, and what measures can Black families take to prevent cancer?

Luckson Mathieu: Yeah, cancer prevention is important because the best treatment for cancer is to prevent it from occurring at all or catch it at the earliest and most curable stage. In addition, cancer prevention offers the most cost-effective long-term strategy to manage cancer's devastating societal impact. As previously mentioned, screening tests can find cancers early when they are treatable and it has the prospect of cure. In addition to regular screening tests, everyday behaviors such as not smoking cigarettes, maintaining a healthy weight, and being vaccinated against certain cancer-causing viruses can all help prevent cancer from developing.

Brielle Collins: Thank you. And Ms. Blakey, going back to some resources, what resources are available to help Black families as they navigate cancer screening and prevention?

Rea Blakey: Well, I'll start with the prevention aspect first. The Centers for Disease Control and Prevention, the CDC, has great resource information for reducing cancer risk. Anyone can share the web page links or even print out materials to hand out to their communities. There's information on the importance of family health history and cancer, on the correlation between alcohol consumption and cancer, cancers related to obesity, smoking cessation resources. And often these resources are culturally curated to meet the needs of a variety of communities, including African Americans, Latinos, LGBTQ. For resources to help families navigate cancer screening, I would recommend that all Americans become familiar with the recommended cancer screening tests that are listed on the National Cancer Institute webpage. It's specific to screening tests. So along with becoming aware of the cancer screening possibilities, you would also want to find a health care provider that you trust. We know trust is a huge issue. And ask questions to help you understand the best cancer screening plan for you. NCI's resource, for example, recommends you ask questions like, are any cancer screening tests recommended for me and which ones? And what's the purpose of the test? Does the test require preparation? How do I do that? These are questions you should be comfortable asking your health care provider and know more about so that you are well equipped to do as much as you can, to make sure that your screening options are actually taken advantage of, and that you do what you can to reduce your risk. You might also want to ask, how often should I have the test and at what age should I stop having that test?

Brielle Collins: Got it. Thank you for that. And I know we touched on this earlier in the podcast, but I just want to circle it back here with National Black Family Cancer Awareness Week. But where can people go online throughout this week? We mentioned that hashtag, #BlackFamCan, but are there other resources available during the week that people can go to online?

Rea Blakey: Absolutely. We have a webpage and a dedicated social media toolkit. So anyone who uses an online search engine and looks up National Black Family Cancer Awareness should see our webpage. On that page, you will find all kinds of resources that include, for example, in the social media toolkit, videos and graphics, as well as a customizable selfie frame for those who are, please do use the hashtag #BlackFamCan. Thank you.

Brielle Collins: Wonderful. It sounds like it's going to be a very engaging week. Thank you for that. And thank you both so much for your time and for sharing your expertise today, Dr. Mathieu and Ms. Blakey. It was so great having you both.

Rea Blakey: Thank you, Brielle!

Luckson Mathieu: Thank you very much.

Brielle Collins: For more information, you can view this podcast on Cancer.Net, where you can also find a link to all the resources mentioned around National Black Family Cancer Awareness Week.

ASCO: Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Cancer.Net Specialty Editor Dr. Petros Grivas talks to Dr. Marianne Dubard-Gault about what people with bladder cancer should know about genetics and genetic testing, including what information genetic testing can provide, how it can inform bladder cancer treatment, and what to expect when meeting with a genetic counselor.

Dr. Grivas is a medical oncologist at Seattle Cancer Care Alliance, clinical director of the Genitourinary Cancers Program, and professor at the University of Washington School of Medicine. He is also an associate member of the Clinical Research Division at Fred Hutchinson Cancer Research Center. Dr. Dubard-Gault is the medical director of the Cancer Genetics Program at Fred Hutchinson Cancer Research Center and an assistant professor at the University of Washington School of Medicine.

View disclosures for Dr. Grivas and Dr. Dubard-Gault at Cancer.Net.

Dr. Grivas: Hello, I'm Dr. Petros Grivas. I'm a medical oncologist and serving as the clinical director of the Genitourinary Cancers Program and professor at the University of Washington Fred Hutchinson Cancer Center. I'm very excited and thrilled today to discuss with one of the amazing leaders in the field of cancer genetics, Dr. Marianne Dubard-Gault, who is my colleague here at UW Fred Hutchinson and has been such a wonderful human being and advocate for her patients and also really a key opinion leader in the field of genetics and the implementation in patient care. Dr. Dubard-Gault, welcome, and I will let you introduce yourself.

Dr. Dubard-Gault: Thank you very much, Dr. Grivas, and it's a pleasure to be here. So thank you for the invitation. I am Dr. Marianne Dubard-Gault. I am a trained oncology doctor and a trained genetics doctor, and my focus now, as Dr. Grivas mentioned, is in the cancer genetics world where I help people either get genetic testing in the first place and/or their family members have interventions for their screening and early detection. I'm also an assistant professor at Fred Hutchinson Cancer Center in Seattle, Washington, and then at the University of Washington on the other side. And I lead the Cancer Genetic Survey Center at Fred Hutchinson Cancer Center. And I have no disclosures.

Dr. Grivas: Thank you so much, Marianne, and again, thank you for helping our patients. And I'm really, really excited today because it's a very important topic, not frequently discussed. And I really, really wanted to make this happen, and thanks to Cancer.Net for helping us getting the word out there. I have no relevant disclosures in this topic. My disclosures are listed on the ASCO website. And Marianne, I will start us off by asking you, just for the audience to set the stage, can you define what we call "genetics"? What exactly are we referring to?

Dr. Dubard-Gault: Yes, that's actually very important. That's probably the first thing that happens in the clinic when we talk to patients is, what is genetics anyway, right? So genetics is the study of the DNA or the genetic makeup that we all have. And that makes a person who they are, right? So looking into the genetic makeup to make sense of it and inform treatment or other interventions.

Dr. Grivas: Thank you much, Marianne. And I think it's so important again for our patients to understand the definitions here. So let me ask you, can you define the difference between a genetic mutation versus genetic alteration? How would you explain that to a patient?

Dr. Dubard-Gault: I think about them in a similar way. So, to me, a genetic mutation or alteration is a spot in your DNA. So there's a long stretch of letters, and there's a spot in there that either was copied or wasn't copied properly over. And so that leads to a command that kind of not being executed properly. And so an example of that would be if I gave you the 2 words "red" and "bed," those 2 words would mean totally different things in your mind. And so if you were supposed to hear "red" and you heard "bed," then downstream will be a different outcome.

Dr. Grivas: Thank you so much, Marianne. And this is very important because for the audience as you pointed out nicely, the genetic code, the DNA translates a message, alright, that becomes a protein and eventually a function of the cell. So if that code, if that message is misspelled, it can lead to different altered and changed-up protein for the cell. That has implications and can potentially predispose someone to cancer. So if we can also help the audience understanding the differences between what we call "somatic genetic mutations" and "germline mutations."

Dr. Dubard-Gault: Absolutely. And this is also something that comes up every time because they're part of the same groups of things overall, right? So somatic means tissue or tumor. And germline, or hereditary, sometimes you'll hear that word interchangeably means inherited or hereditary or part of the genetic makeup or the code that you were born with. So different parts of our body have different genetic mutations. And that is why even with 2 identical twins, they won't have the same moles on their skin, or they won't have the same medical conditions, even if they have exactly the same genetic code. And it's exactly the same for a person who has a tumor, right? The DNA or the genetic makeup they were born with will stay exactly the same as they grow older, but the genetic makeup their tumor has as the tumor grows can change and make more or have more mutations. So testing different parts of the body will help tease out which ones of the mutations are located where? Is it in a tumor only? Is it in the genetic makeup you were born with or is it part of that transition between the 2?

Dr. Grivas: Thank you, Marianne. I think this is great when we explain to the patients what exactly mutations, alterations, means, and the difference between a somatic tumor testing, as you said, mostly to help define treatment options. And what you very nicely discussed are germline testing, looking at hereditary predisposition to cancer that can impact the patient and also family members and the broader family. And one kind of take-home message may be for our audiences, when someone is about to see an oncologist or their provider, is greatly helpful if they can do quote-unquote "their homework" and try to understand and delineate and capture as much as possible regarding the family history. And sometimes it's hard, especially when you go to distant relatives, cousins, nephew, nieces, it's more difficult, but it can help a lot and inform that discussion and whether a referral to a genetic counselor or geneticist is relevant. So that's what we try to do with nurse navigation these days to help inform people with cancer before their appointment how they can maximize to capture that information, it can be helpful to them and for the provider. And the next question, Marianne, is how common are these genetic germline mutations in people with bladder cancer?

Dr. Dubard-Gault: I think the answer is still out there. We don't have the complete answer today. We don't know all the genes that are implicated in bladder cancer today. So given that, we probably don't have the full or complete answer as to how many people with bladder cancer would have it. But kind of to get close to the answer, as close as we can possibly be today, I think it depends on the group of patients with bladder cancer that you test, but I would probably give a 1 in 10 people with bladder cancer would have an inherited genetic mutation.

Dr. Grivas: And that's very helpful Marianne. And of course, varies, of course, across the different scenarios and the family history as you mentioned, the age of cancer diagnosis. And sometimes it's interesting in patients with urothelial carcinoma, cancer in the upper urinary tract, like renal pelvis, kidney problems, or ureter, there seems to be some higher frequency of germline mutations in that as opposed to bladder cancer. Of course, it can happen in that scenario, but seems to be some higher frequency in the upper tract cases, is that right?

Dr. Dubard-Gault: I agree. Not all cancers are created equal, right? In the bladder, that's probably also true. So depending on where it starts, the type of cells that are involved, and how the person was born with certain genetic predispositions, it may very well affect how all of these are linked together in one line of event versus maybe something that happened randomly or occurred that we don't have a one specific answer or a combination of answers.

Dr. Grivas: That's a great point. And obviously, there are the huge impacts that we discussed to help prevent cancers in the bladder family. Cancer prevention mode, I call it, when I explain to the patients before they see you. And also, some patients are also asking, in addition to that family benefit in my brother's family, is there any potential impact on the treatment selection for the bladder cancer? Any comment?

Dr. Dubard-Gault: Yes, I do believe there is actually more today than ever before, especially with the new medications that have come around, right? So sometimes a genetic mutation will happen in the DNA or the code that is important for repairing the code of the DNA, or sometimes it will happen in an area that helps boost the immune system or the response to the cancer cells by the immune system. So in that case, if we find a genetic mutation, then we can use a chemotherapy that concentrates or targets that area that's not working well and fix it, right? So that's one really important area. And then another area, and Dr. Grivas, I know you've done a lot more clinical trials and studies that involve the DNA that makes new blood vessels for feeding the tumor. And in that case, you can use a chemotherapy that would block the body from making those new blood vessels and basically shut off the feeding system to the tumors. And so that way, the genetic testing can also help the patient find a therapy that would work better for them.

Dr. Grivas: That's a great discussion. And we're doing many clinical trials to test this hypothesis. This assumption kind of practice, and we try to look at particular therapies that might be relevant in the context of a germline mutation. And those clinical trials are very promising. And I always encourage our patients to consider subsequent trials. And the other aspect of it, as you said very nicely, is that a patient who may have some changes in the code encoding some enzymes, some proteins that repair the DNA, this can cause some more mutations. And in this particular scenario, there may be a much higher response to immunotherapy. That immunotherapy may help shrink those tumors with what we call more unstable genomes. So that's very interesting to see that across tumor types, to your point. The other question is if someone is referred to genetic counseling, how can they be better prepared for their appointment?

Dr. Dubard-Gault: I think the most important thing that I would say is to really embrace it and go. Because it's often something that makes people worried that they have a genetic predisposition in the family, and they may not necessarily be ready to hear it or want to have as much information, especially being diagnosed with a cancer at the time. And so really embrace it and go for the genetic visit because it is something that could be very useful and bring information not only to you as a person for your own treatment, and/or then for your siblings or relatives for them to have access to interventions they would not have otherwise.

Dr. Grivas: What question do you think people should ask their providers? How can they better prepare for the visit with the provider overall regarding the topic we are discussing today?

Dr. Dubard-Gault: That's also very important because as much information as you can gather is really important. So, if possible, gathering as much information about your family history as you can, as Dr. Grivas mentioned. And sometimes you can't have all the information, some grandparents died, they did not share the information about their cancer diagnosis because they didn't want to upset the family. Sometimes you have no information on one side of the family because you don't know who your father's parents are, for example, or a certain relative may be OK now and they have cancer later on, and you will probably not have that information, right? We can still do the genetic test knowing that some of this information is missing. So keeping in mind that as much information as you can get is good. And if we have a lot, that's helpful, and if we don't, we will kind of factor that in our conversation. And a few other tips I would keep in mind is the timing of the testing matters. Sometimes doing the testing earlier in the process is a good thing because it takes a little while for the results to come back.

That's a sophisticated test that takes usually 3 to 4 weeks. There are many different types of genetic testing; that's also very important. You may very well have more than 1 genetic test, as Dr. Grivas mentioned. The test on the tumor, the test on your genetic makeup from a blood sample or a saliva sample. I mean, keeping in mind-- I think the third one that's really important is keeping in mind that when we do the genetic test, the results may implicate other people in the family straight away. And I'll share an example of this because this comes up in my clinic very often. So I met a brother not so long ago who had bladder cancer. No exposures, no smoking, nothing to point to a risk of bladder cancer for him, but his sister had uterine cancer earlier on before the age of 40, and then had colon cancer as a second primary cancer. And the test came back with the genetic predisposition we talked about, Lynch syndrome. And this diagnosis basically explained his cancer diagnosis on why he had an unstable genome in his tumor. And his sisters, both of his sister's cancer. So by proxy by testing him, we tested not only him, but his sister as well, even if we'll do the sisters confirmation tests, we know the sister is likely positive for this.

Dr. Grivas: Thank you so much, Marianne. The very useful information. Again, the positive impact and benefit for the broader family. What happens during and after the initial meeting with the genetic counselor or the geneticist?

Dr. Dubard-Gault: Well, I love genetic counselors, I think they're very helpful. And I work with them on a day-to-day basis. So, what they'll do is they'll sit down with you either in person or telemedicine or telehealth from the comfort of your own home or on the phone. I don't like the phone as much as I like the interpersonal connection with a person. But they'll help you draw out your family tree, put all the people in the family on the page together to kind of see and share a pattern. They'll talk a little bit more about the different types of genetic testing one person could have. And then they'll facilitate getting the genetic test that is best for you and your family. And so that really is the most important piece because they'll work with your oncology doctors and other doctors to come up with the best option.

And the one that matches the family story. And then if you're in person, you could even provide a sample, either a blood sample or a saliva sample, right there. And then the authorization and all goes through, and then the results usually will come back a few weeks later. And then the genetic counselor or myself as a genetics doctor will sit down with you when the results come back to review what they mean, not only what the actual test says, but what they mean specifically for your treatment, and/or for yourself or your screening and interventions later on, and/or your family members, if they need to be tested themselves or what needs to happen for them. And then you can obviously be referred to a specialist like Dr. Grivas or others for a colonoscopy or for thyroid ultrasound or some other tests that may be needed for these screening interventions in the future.

Dr. Grivas: Great points. And as you mentioned before, it's important for the patients who see the provider to discuss their family history-- close and distant family history as much as they can, and they can even ask whether they need to see genetic counselors. Sometimes the patients can remind a busy provider how important that is and ask for a referral, it's definitely important to ask the provider.  Very quickly, Marianne, you mentioned before the value of testing for both the patient and the broader family in terms of what we call cascade testing and cancer prevention. You mentioned the example in your patient, can you very briefly comment on that and what is the value here again for the patient and the family?

Dr. Dubard-Gault: Absolutely. And sometimes someone with a genetic predisposition, so someone born with a genetic predisposition to cancer, can be at risk of more than 1 cancer in their lifetime. So sometimes, when they're diagnosed with the cancer, we find this genetic predisposition to said cancer, but it may come with other cancers as well, just like the bladder cancer and uterine cancer and colon cancer. And this may not be something a person would want to hear when they're diagnosed with cancer, but it is good information that will stay there for the future as they go through the treatment for having interventions done, right? So it's good information to talk about with their doctors so their doctors can order the colonoscopy or different screening protocol. We'll recognize a certain intervention like removing the uterus of someone in the family so they would reduce their risk of uterine cancer. And obviously, genetic mutations tend to be shared in the family. It's most likely something was inherited in the family rather than new in a person. So each person who's positive for a genetic predisposition, we think about their siblings, their children, their nieces and nephews, and those people may have exactly the same genetic predisposition or mutation, and they may be at risk of the same kinds of cancers. And that's the reason why they would get this information to be eligible for other screenings as well. And interventions.

Dr. Grivas: Very important, and very useful for the patient. Before we wrap up, Marianne, can you comment a little bit on barriers to testing, out-of-pocket costs, culture, trust, literacy, busy practice, competing priorities?

Dr. Dubard-Gault: Yes, absolutely. I think the main ones are awareness that bladder cancer can be a genetic cancer. It's really rare, but it can be. And so keeping that in mind, because then if you're not even referred or that doesn't come to mind, it may not get us to doing this genetic testing. The diagnosis of cancer is a lot to take in, right? So it may not be the right time to do it right away, but keeping that in mind for the future is also important. The cost. Sometimes the generic testing isn't covered by Medicare, unless there are specific criteria that we talked about, a family history of specific type or early diagnosis and all these things. And the genetic counselor will really help push to find as much information as possible to get the test covered. And there are lower-cost options out there. And I think the last 2 are really the privacy of the results. People worry that this information will be shared outside of health care, and/or sharing themselves this information with their family members when they're probably or maybe not ready to disclose their cancer diagnosis. So I find that that's maybe less or lower on the list, but in order to keep in mind as well.

Dr. Grivas: Thank you, Marianne. Maybe the last 2 very quick questions for you. Germline testing and options and value of counseling. I know you have touched upon that already. But did you have any departing thoughts on that part on the value on the patient and the family and any other considerations, for example, DNA biobank, etc.?

Dr. Dubard-Gault: Absolutely. So, I find that meeting with the genetic counselor, even after you've had genetic testing and the results are back, is a valuable thing to do. And not necessarily right away, but later on down the road, right? So because this field, the genetics field, advances rapidly, it's possible someone will be testing again or there are more genes or more mutations out there we weren't testing for a few years ago that we would test again. So keeping in mind, we can test again. And that meeting with the genetic counselor is always useful even if you have heard a little bit about it already. And then the DNA biobanking piece, if that's a service that's available to you, keeping your DNA for the future, when the technology is not advanced yet, is very important because we know for sure the knowledge will change and will bring new treatments and new options for screening and interventions, so keeping the DNA for the future is very useful.

Dr. Grivas: That's a great point. And because technology is evolving very fast, the methodologies are changing, many times we have the information and genetics team, and counselors and geneticists try to keep track and follow those people who are tested to see if any of the information may potentially make a mutation that was of a certain significance-- something that may be significant down the road as more information are coming in. And because of this rapidly evolving nature of information, it is good for people with cancer and also any affected family members to stay in touch periodically and follow up with the genetics team. Maybe the last question for you, Marianne, is if you have any take-home message for our people, our audience today so they can remember going forward.

Dr. Dubard-Gault: Information is power. It really is. And having this information helps your doctors bring the best treatment to the tumor that you have and not somebody else's, right? And for the family, that may bring an answer that was longed for really generations before you, and that would help not only have this information, but take it forward and say, "You know what? I'm going to do something about it because we can." So to me, that's the reason I transitioned careers, and that's the message that I want to keep sharing.

Dr. Grivas: What a great message by Dr. Dubard-Gault. And now we're trying hard to involve and engage genetic counselors and geneticists to our multidisciplinary clinics. And bladder cancer is a great model for multidisciplinary approach, and we try to engage them earlier. So we need more of you, Dr. Dubard-Gault. We need more geneticists and genetic counselors. And with your background in oncology, it's fantastic to work with you. Thanks again for a great discussion. Thanks again to Cancer.Net for all they do for the mission of patient education and of course ASCO. And thanks to the audience for your attention today. Thank you.

Dr. Dubard-Gault: Thank you for inviting me.

ASCO: Thank you, Dr. Grivas and Dr. Dubard-Gault. Learn more about genetic testing and cancer at www.cancer.net/genetics. 

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Allison Magnuson talks to Beverly Canin, a cancer survivor and patient advocate, about the importance of specialized cancer care for people over 65. They discuss how the health care team can assess and provide specific support for people over 65, why people over 65 should be included in cancer research, and tips for people with cancer in this age group.

Dr. Magnuson is an associate professor of medicine and a board-certified medical oncologist and geriatrician at the University of Rochester Medical Center. Ms. Canin is a patient advocate, research partner, and the co-chair of the Cancer and Aging Research Group's Stakeholders for Care in Oncology & Research for Our Elders Board, or SCOREboard. Dr. Magnuson is the Cancer.Net Associate Editor for Geriatric Oncology, and Ms. Canin is an advisory panelist on the Cancer.Net Editorial Board. You can view their disclosures at Cancer.Net. 

Dr. Magnuson: Hi, I'm Dr. Allison Magnuson. I'm a geriatric oncologist from the University of Rochester, and I'm here with a good colleague and friend of mine, Ms. Beverly Canin, who is a patient advocate that I work closely with in geriatric oncology. And we're here today to have a conversation about why geriatric oncology is important, and what advice Beverly would have for older adults with cancer as they're navigating the cancer care process. Beverly and I do not have any relevant relationships to disclose. Good morning, Beverly, how are you?

Beverly Canin: Good morning. I'm very happy to be here. I'm well, thank you. And looking forward to our conversation.

Dr. Magnuson: Me too. Beverly, I thought maybe we could start by you just sharing your story about how you became involved as an advocate in geriatric oncology. I think it's such an interesting story. So I'd love the listeners to hear about that.

Beverly Canin: I'm very happy to do that. I was originally diagnosed with breast cancer in 2000. And for over 10 years, I was a very active advocate for breast cancer doing support for individuals of all ages and also peer review in the California Breast Cancer Research Program, the Department of Defense Breast Cancer Research Program. I worked in NCI, National Cancer Institute, committees and with the FDA. And in all those years of doing both personal support for breast cancer patients and committee work at national, state, and local levels, I was never made aware of special issues for older adults with cancer until I heard a session at the Annual Meeting of ASCO, the American Society of Clinical Oncology. I had been attending that Annual Meeting, but had never noticed that there was a session on cancer and aging. I was attending sessions that pertained to breast cancer only. And I was kind of blown away at what I heard and the fact that I had been an advocate for so long and didn't understand that there was such severe issues pertaining to cancer care for older adults. And it seemed to be based on 2 basic concepts or realities. In simplistic terms, it was that older adults were systematically ineligible for clinical trials, which meant that the results of clinical trials didn't necessarily apply to older adults. So treatments were being recommended that were based on a different population. And the other thing that struck me was that oncologists didn't have any training or minimum training in geriatrics, and geriatricians had little or no training in oncology. So that's what really caused me to see what I could do as an advocate to address these issues.

Dr. Magnuson: That's great. And you know those are some of the reasons why I am so passionate about geriatric oncology and really trying to move forward research about how to best care for older adults with cancer and ensure that older adults are included on clinical trials. I think delving into that piece a little bit more, Beverly, thinking about members of our audience that might be older adults who are talking with their oncologists about treatment options, knowing that some treatment options might be less studied in older adults or there may be less data. Do you have advice for your patients when they're talking with the oncologists about kind of how to talk about this and how to ask questions about how they might tolerate treatment or respond to treatment in that regard?

Beverly Canin: Well, of course, the first thing is to know what studies they're basing their recommendations on. And whether they included older adults in the results of the study. And unfortunately, all too often, we're going to find that the answer is going to be no. So, unfortunately, it really is incumbent upon patients to advocate for themselves and to do some research. And there are places, of course, here at Cancer.Net, and it is a very good resource. We also have the Cancer and Aging Research Group, which I have worked with now for over 10 years. And on their website, there is help and suggestions for older adults with cancer. The basic idea, I think, no matter who the patient is, is to have someone with you to make notes so that you can look back and study later. And to also understand that in most cases, there is time to make decisions. We tend to get very panicked about any kind of cancer and some, obviously, are much more aggressive, much more quickly than others. But for the most part, there is time to do a little bit of research and not make decisions hastily.

Dr. Magnuson: I think that is such important advice. Yeah, always bringing extra supports to help kind of absorb the information too is so key and really being able to have somebody to talk to about kind of that information in the context of your own personal goals and preferences is so important. And I agree also that patients and their support system can be such an advocate about aging-related issues or concerns that they might have that kind of interface with their cancer treatment plan. And I know ASCO and also the ACCC [Association of Community Cancer Centers] are really working hard to kind of disseminate information into academic and community oncology practices about caring for older adults with cancer. So I think we're all working hard to kind of spread that knowledge and patients can help us in that too.

Beverly Canin: It just occurred to me, it's really important also to understand that one of the primary issues and the thing that really needs to be explored with older adults with cancer is what are their goals? What's their hope for their life? Are they more interested in prolonging their life no matter what that means or in the quality of their life? And we have to remember with older adults or with anybody, we actually have 3 ages. We have a chronological age, we have a biological age, and we have a functional age. And those vary with every individual. I mean, the chronological age is fixed. That we know. But what that means for your biology or for your function is not relevant at all. And that is something that has to be explored and that patients need to be thinking about themselves because some patients are willing to tolerate toxicity for a short term in order to extend their life for varying periods of time. To me, a 2-month extension of my life might be very valuable because there may be something that I wanted. I may want to go to a wedding or see my granddaughter graduate or whatever it is. There may be a specific goal that I would like to live to see, but for someone else, that may not be important. They don't want to undergo that kind of toxicity because it may also impair your function or probably will impair the function.

Dr. Magnuson: I think that's so well said. Yes. And I think it's important for us to kind of comment on how doctors do have ways to talk with patients to assess their functional age and really kind of help understand where patients are coming at in relation to their chronological age. And how that might relate to kind of treatment and also supports that we might put in place to try to optimize that treatment experience. But your advice on the goals and values and talking about what your values are with your oncologist, I think, is so important. And really, no matter what your age is.

Beverly Canin: Right. And be honest. Be honest. Sometimes we are reluctant to discuss these things, and that can be a real impediment to the right choices for treatment. And it's not always easy to be honest with yourself. You have to really think of yourself, and your family, those who are also affected by what happens to you. And so it is complicated. It isn't easy. It takes determination. And it's good to be fearless as a patient and not be intimidated by your physicians, by your doctors.

Dr. Magnuson: Yeah, I heard a colleague once say that really, patients are the experts on their own bodies, right? And their own goals and preferences. So really, they are the experts there, right? And so kind of having that knowledge really makes patients such an important, that perspective is so important in the conversation. So making sure there's time and space to talk about that is really important.

Beverly Canin: I also appreciate the clinician who admits that they learn from their patients and that it's impossible to keep up with everything on their own and that they really need to learn from their patients so they appreciate what patients can bring to them.

Dr. Magnuson: Absolutely. Yeah. Beverly, we talk a lot about what we refer to as supportive care during treatment, meaning kind of aside from just the cancer treatment, all the extra things that we might put in place for patients to try to help them through their cancer treatment journey as well as survivorship journey. And sometimes, as a geriatric oncologist, I'm really using information about aging-related things. Maybe physical function or cognitive status. I wonder if just from a patient standpoint, you might comment on kind of why some of those aging-related aspects might be important in our cancer care and how doctors might create a supportive care strategy for patients.

Beverly Canin: I think we're beginning to learn how to do this. I think that's an aspect that has been missing for a long time in intensive care, not just for older patients, but especially for older patients where there are all kinds of issues. And we have not mentioned specifically the geriatric assessment. But this is an important way of getting to these issues. And unfortunately, again, it's something that may be used in academic centers, but you're not finding that this is happening throughout the health care system. And it's very, very important that you use some kind of tool to assess these different ages that we refer to on each patient. And we know that there are several. We know one that is used quite frequently is the one that is found on the Cancer and Aging Research Group site, or CARG site, and which has been validated and used widely. But again, not widely enough, but it is a good way to get to these different issues that are not strictly medical.

Dr. Magnuson: I always use an example of if we have an older patient come in and we assess how their balance is and how quickly they're able to walk, that helps us estimate, are they at an increased risk of falling at home? Because we know a fall can really be a life-changing event. And starting on cancer treatment or chemotherapy might increase our risk for falls. So we really want to be aware of kind of all of those other aspects that might interplay with the cancer treatment so that we can try to head those off and mitigate them. So sometimes we might refer patients to physical therapy to try to improve their balance and strength as we're starting on that cancer treatment journey to try to lower that chance of falling. And I think the most important step is kind of assessing that, as you said, and figuring out where are those vulnerabilities and how can we intervene to try to help support patients in those spaces better?

Beverly Canin: The other thing patients can do is to connect with other patients who are going through what they're going through. And there don't seem to be specific support groups for cancer and aging or organizations that are focused on older adults with cancer. I'd like to see that happen so that we do have that resource available. But for the moment, I think, for the most part, it's a matter of through whatever organizations there are, if they have support groups, to join the support groups and try to meet other patients who are older adults.

Dr. Magnuson: Excellent. I would love to hear your thoughts on research, Beverly. You've been so active as a research advocate and we've worked together, collaborated in that space. But I'd love to hear your advice for patients, older patients who are considering clinical trials, or supportive care research studies. What recommendations you have to them about participating in research and why that might be important.

Beverly Canin: Oh, it's very important as I mentioned early on. One of the issues that is still prevalent is that the eligibility criteria for participation in clinical trials traditionally excluded older adults for reasons that didn't really make any sense. It was fear of comorbidities. Older adults are likely to have other illnesses as well. So they were feeling it might confound the results to have this mix, which didn't make any sense at all. And so now we don't have upper age limits on most clinical trials. But there is a need for patients to engage in clinical trials. And I think there are a lot of misconceptions about participation in clinical trials. And particularly, any of those that have to deal with medical treatment, that patients feel like, "I want to know what I'm getting. I don't want to go into a clinical trial that is having some people on a drug and some people are not on a drug, and I don't know which group I'll be in." But what I think is behind that concern is that you might not be getting the best care that's available at the time. And that's not true because any clinical trials you have to be assured that the participants have at least existing standard of care. And so I think dispelling myths such as that.

The other thing, which you're bringing up, is that there are many, many, many trials that are so important about supportive care for older adults with cancer. And because these are the issues that fall by the wayside, but really, really influence how patients are going to respond to treatments. And so I think it's really, really important for older adults to ask their doctors about clinical trials, if they're eligible for clinical trials, and really consider participating in clinical trials. Many older adults will do so not for themselves, not expecting of results to be helpful to them, but for the future generations, to help future generations. And it's very, very important to think in that way, think in those terms. It's also important to find out, if you do start investigating any clinical trial, to find out what the costs might be to you. The ideal situation is that the patient will incur no cost at all, but we have found that that is not always true. And so it's really, really important to investigate that and understand if there is a risk of incurring any expense, which most patients can't do. And understandably.

Dr. Magnuson: Thanks, Beverly. We've talked a little bit about where patients might be able to go for more resources about cancer and aging information, but I'd love to highlight that. So if you have some just suggestions for patients where they might be able to access that information?

Beverly Canin: We don't have cancer support organizations the way we do for breast cancer or lung cancer and of the association that supports that. We don't have one that does that, but the best sources, I think ASCO here in Cancer.Net is providing information for patients. The Cancer and Aging Research Group website also has a page with information. The SIOG, the International Society of Geriatric Oncology, also has a page for patients. So it's really a matter of addressing the organizations that are focused on cancer and aging, for mostly focus for the research, for the scientists, but many of them also have pages that help patients. And ACCC I believe as well is a source for that.

Dr. Magnuson: Absolutely. Great advice. Lots of resources out there for patients.

Beverly Canin: Yeah, I mean, I wish it were easier than that. It's what we need to develop. We really do need to develop that. But we do have a group, we're engaging patients more and more in research, not as participants in the research but as partners with the researchers. This has been a very, very important development in advancing the issues and improving the research that is being done about cancer and aging.

Dr. Magnuson: Absolutely. As a researcher myself, who's worked with patient advocates and what I refer to as research collaborators, my partners on research, I can't emphasize that statement enough. It has been a critical part of my learning as a researcher and I think really strengthened all of our studies here at Rochester, for sure.

Beverly Canin: We have formed a research group called SCOREboard, Stakeholders For Care and Oncology and Research for our Elders, which is composed of older adults who are in treatment or were treated for cancer as older adults. And caregivers of such patients as well as advocates. And it has been very, very effective. We've been in existence now for over 10 years, about 12 years. And work very closely with the CARG researchers.

Dr. Magnuson: Well, thank you so much, Beverly, for chatting today about this. I hope there were some pearls of wisdom that our listeners were able to take away from you, and I always enjoy talking to you so much. I feel like I learn more every time, Beverly. So thank you for making the time today.

Beverly Canin: Well, I thank you for having me and giving me this opportunity to share my story.

ASCO: Thank you, Dr. Magnuson and Ms. Canin. Learn more about cancer care for adults over 65 at www.cancer.net/olderadults.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Norah Lynn Henry covers new research in breast cancer treatment, prevention, and survivorship presented at the 2022 San Antonio Breast Cancer Symposium, held December 6-10.

Dr. Henry is a Professor and Interim Chief of the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center in Ann Arbor, Michigan.

View Dr. Henry's disclosures at Cancer.Net.

Dr. Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates from the 2022 San Antonio Breast Cancer Symposium. I have no conflicts of interest for any of the trials that I will talk about today. First, I'm going to give a very brief overview of the types of breast cancer, and then talk about some research that was presented on both metastatic and early-stage breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We treat those cancers with anti-estrogen treatments, which block estrogen or lower estrogen levels. We often combine anti-estrogen treatments with other medications to try to make them work even better against the cancer. Other breast cancers are called HER2-positive. These are often more aggressive cancers, but because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or HER2 receptors. These are called triple-negative breast cancer and are also often fairly aggressive cancers.

One of the most exciting takeaways from the San Antonio meeting was the promise of new medications on the horizon to treat hormone receptor-positive, HER2-negative metastatic breast cancer. A commonly used treatment for metastatic breast cancer that is hormone receptor-positive and HER2-negative is fulvestrant, which is a type of medicine called "SERD," or selective estrogen receptor degrader. At the meeting, we heard new data about 2 new SERD medications: elacestrant that was tested in the EMERALD trial and camizestrant that was tested in the SERENA trial, both of which are oral pills instead of injection medications and both of which may work particularly well against tumors that have mutations in the estrogen receptor called ESR1. In addition, we heard about capivasertib, which is an AKT inhibitor that was shown to work well when combined with fulvestrant and had less toxicity than some of the similar drugs that had previously been tested.

For treatment of HER2-positive metastatic breast cancer, there are now a lot of medications that have been FDA approved, so some of the questions that clinical trials are now examining are related to what order we should use the medications in when we are treating patients. We heard about 2 studies of the medication trastuzumab deruxtecan, which I'm going to refer to as Enhertu. This drug is a combination of the anti-HER2 antibody trastuzumab plus a chemotherapy drug, and the antibody targets the drug to a cancer like a guided missile. Enhertu is currently routinely used to treat patients with metastatic HER2-positive breast cancer. We heard updated data that showed that when Enhertu was compared head-to-head against trastuzumab emtansine, also known as Kadcyla, patients who were treated with Enhertu were able to stay on the medication for a lot longer compared to patients who were treated with Kadcyla. We also heard that for patients who had already been treated with Kadcyla but it was no longer working, it is reasonable to switch to treatment with Enhertu at that point, because it is still likely to be effective. These studies may help oncologists decide what order to use these newer medications when treating patients with HER2-positive breast cancer.

To switch gears a little bit, I'll now talk about another study I found interesting. This one is in the setting of people who are at high risk of developing breast cancer, but who haven't actually been diagnosed with cancer yet. In general, people are recommended to take either tamoxifen or an aromatase inhibitor medication, which is the same as treatment for patients who have been diagnosed with hormone receptor-positive breast cancer. But in this case, it's trying to prevent them from ever getting breast cancer in the first place. However, many people don't take the medications because they are concerned about side effects. A study was therefore performed in Italy that compared the 5-milligram dose of tamoxifen, which is only one-quarter of the full dose, with placebo for 3 years. After 7 years of follow-up, this low dose of tamoxifen, which is being referred to as "babytam," was shown to reduce the risk of developing breast cancer by about half, which is similar to the effects seen with the full dose of the medication. Plus, there were fewer side effects. This lower dose is likely to be used regularly for prevention of breast cancer based on these findings, although this lower dose of tamoxifen has not yet been tested to see if it is as effective as the full dose of medication for preventing breast cancer recurrence, so it is not routinely recommended for patients who have a diagnosis of breast cancer to receive this lower dose.

Finally, I will touch briefly on exciting results from the POSITIVE trial, which is a trial conducted around the world that examined whether it is safe for young women with hormone receptor-positive breast cancer to stop taking anti-hormone therapy to become pregnant. The women on this trial stopped taking endocrine therapy after taking it for about 18 to 30 months, and then spent up to 2 years trying to become pregnant. About three-quarters of the patients had at least 1 pregnancy during that time, and importantly, there was no increased risk of breast cancer recurrence seen in these patients. Once patients were done with their pregnancy, it was recommended that they restart taking endocrine therapy again.

There were a lot of other research findings presented that were related to treatment for both early-stage and metastatic breast cancer at this meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, including the 3 that I mentioned already. And we eagerly await the results of large, randomized trials so that the drugs that work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2022 San Antonio Breast Cancer Symposium. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you.

ASCO: Thank you, Dr. Henry. You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Christopher Flowers covers new research in non-Hodgkin lymphoma presented at the 2022 American Society of Hematology Annual Meeting, held December 10-13 in New Orleans, Louisiana.

Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and was appointed Division Head ad interim of Cancer Medicine in August 2020.

View Dr. Flowers' disclosures at Cancer.Net.

Dr. Flowers: Hello and welcome to this Cancer.Net podcast. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center. And it's my great pleasure to talk to you today about updates in lymphoma from this year's American Society of Hematology meeting in December of 2022. I have a number of disclosures related to my work as a consultant for companies in the development of therapies for lymphoma. I will not talk about agents specifically related to those companies, but 2 companies that overlap with some of the areas that I'll talk about in bispecific antibodies includes Genentech, Roche, and Genmab, as well as research support from those companies for research that is performed at MD Anderson. So this year's American Society of Hematology meeting had a number of highlights. I was very fortunate to be the introducer for one of those key highlights, and that was the abstract presented at this year's plenary session. This was actually the first abstract presented in the plenary session where I introduced the abstract and set the context, and Dr. Martin Dreyling from the German group described the TRIANGLE study. So the TRIANGLE study was a randomized controlled clinical trial, meaning that the trial was performed in a randomized fashion to be able to test 3 particular strategies for patients with mantle cell lymphoma.

Mantle cell lymphoma, as many of you may know, is a relatively uncommon form of non-Hodgkin lymphoma. It's a kind of lymphoma that can be quite aggressive, and particularly for younger patients who are suitable for aggressive therapy, the role of autologous stem cell transplantation has been something that's been important for the first-line therapy for mantle cell lymphoma. This study evaluated the use of a standard regimen of giving R-CHOP chemotherapy alternating with R-DHAP chemotherapy. So a chemotherapy regimen that includes Ara-C as their component followed by autologous stem cell transplantation. And it compared using that same regimen to giving it with ibrutinib added to the R-CHOP portion of the chemotherapy, followed by ibrutinib maintenance after the stem cell transplant or another experimental arm that added ibrutinib to the R-CHOP portion of the chemotherapy and gave 2 years of ibrutinib maintenance without stem cell transplantation. I think, importantly, this arm compared to each of those 2 experimental arms versus the standard of care and showed graphically that both of the arms that contained ibrutinib, the BTK inhibitor, looked to have improved failure-free survival compared to the standard stem cell transplant arm. Formal statistical tests were performed to compare the arm that included transplant plus ibrutinib showing that that was superior to transplant alone. And it remains to be seen whether that arm is superior to the arm that used ibrutinib alone.

But those 2 arms look fairly similar in terms of their outcomes, and also the toxicity associated with the transplant obviously was substantially more than performing the therapy without transplant. This suggested perhaps autologous stem cell transplantation can be removed from frontline therapy for patients with aggressive mantle cell lymphoma and provides provocative data that may help to change practice, both in Europe and in the United States, as well as the rest of the world.

A few other abstracts that were presented at this year's ASH meeting presented provocative data about ways to be able to improve the ways that we predict outcomes for patients. Matt Maurer presented the results of the Follicular Lymphoma International Prognostic Index 24, or the FLIPI24, as a risk factor to try and predict patients who might have early progression of disease with follicular lymphoma. One of the things that we know is that when you look at patients with follicular lymphoma, those patients who have progression of their disease within 24 months of the start of chemoimmunotherapy are patients that have markedly worse outcomes. And Dr. Maurer and our colleagues led an international study showing that a new prognostic factor model that included age, hemoglobin, white blood cell count, normalized lactate dehydrogenase, and beta-2-microglobulin, so all laboratory values that are connected within routine clinical practice, along with age, were a better predictor of this early progression of disease. This may serve as a useful model moving forward to help patients and their providers to understand who are the patients who are at higher risk of having aggressive behaving follicular lymphoma, and eventually, we can make strategies that help to address that for those patients.

A second provocative model for using integrated genomics helps to identify patients who also have early progression of disease, and those are for patients with diffuse large B-cell lymphoma. This was presented by Kirsten Wenzel from the Mayo group, where Anne Novak was the senior author for this publication. What they did was they integrated the genomics into the clinical prognostic factors and found that there was a particular RNA-seq profile that helped to identify those patients who had early progression of disease with diffuse large B-cell lymphoma. They compared this approach to other prognostic models and suggested that these approaches may be able to improve upon the prediction of outcomes and be incorporated into the ways that we predict treatment strategies for patients with diffuse large B-cell lymphoma in the future. While these are still early on in their development, I think this holds promise for the future management of patients.

And then the other class of agents that I'll mention from this year's ASH meeting are the bispecific antibodies. There were several abstracts that addressed this, both in patients with relapsing, refractory, diffuse large B-cell lymphoma, and in patient populations with relapsing refractory follicular lymphoma. One of those highlighted came from Nancy Bartlett, who discussed the role of a specific bispecific antibody for patients with relapsed follicular lymphoma. And I think these agents hold broad promise. So I appreciate your time and attention and hope you enjoyed this podcast and look forward to talking to you in the future about new developments in lymphomas broadly.

ASCO: Thank you, Dr. Flowers. You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, esophageal cancer survivor Rachael Kearney shares her story with Dr. Frank Penedo, Associate Director of Cancer Survivorship & Behavioral Translational Sciences and the Director of the Cancer Survivorship Program at the University of Miami Sylvester Comprehensive Cancer Center, and an Advisory Panelist on the Cancer.Net Editorial Board.

They discuss her podcast, Call On Courage, which features conversations connected to courage, starting over, and overcoming. They also discuss the value in sharing your story, and tips for people with cancer and survivors.

You can view disclosures for Dr. Penedo and Ms. Kearney at Cancer.Net.

Dr. Frank Penedo: Hello, I am Frank Penedo. I am the associate director of cancer survivorship and behavioral translational sciences and also the director of cancer survivorship and supportive care programs at the University of Miami Sylvester Comprehensive Cancer Center. I'm also an advisory panelist on the Cancer.Net Editorial Board. Today, it is my pleasure to welcome and talk with Rachael Kearney. Rachael is an esophageal cancer survivor who lives in Manchester, England. After she received her cancer diagnosis, Rachael started a podcast called Call On Courage, which features conversations connected to courage, starting over, and overcoming in general. Rachael, thank you so much for talking with us today.

Rachael Kearney: Thanks for having me, Frank. I'm excited to get into this conversation.

Dr. Frank Penedo: Before we begin, Rachael, I should mention that we have no relationship to disclose related to this podcast today. Rachael, can you please tell us a little bit about your experience being diagnosed with cancer and your journey thereafter and what was it like?

Rachael Kearney: Yeah, so this is kind of coming into about 15 months ago. Out of nowhere, I had sort of severe acid reflux. And I was due to meet up with some girlfriends in Manchester, and I was just really struggling to eat my breakfast. It was just bizarre because I've not had those type of symptoms before. And essentially, what happened very quickly, within a 3-week period, this acid reflux increased, and it got worse. And it got to the point where I couldn't tolerate water. So I knew something was seriously up. But there was a waiting period before I got admitted to hospital, before I could have an endoscopy, which is obviously what I knew was going to get to the bottom of things to find out what was going on. And, yeah, it was just very scary in terms of not being able to tolerate normal food. But essentially, when I did get admitted, the endoscopy appointment came a lot quicker within a matter of 2 days, and then the actual diagnosis of esophagus cancer was within 24 hours after that. Obviously, it was just a massive shock because there wasn't a history of this in my family. And at the time, I was only 42. I'm 43 now. And it just felt very bizarre because I hadn't heard of anyone else that had esophagus cancer in my age group or friendship circles or whatever.

Dr. Frank Penedo: Yeah, you mentioned, Rachael, a couple of words in there that stand out. It's just a shock of that diagnosis and, of course, the fear that comes along with that. It sounds like you were able to get proper attention pretty quickly, which is obviously very important when dealing with a cancer diagnosis. But can you tell us a little bit about how you dealt with that initial shock and fear?

Rachael Kearney: So the weird thing was I was in shock, but I wasn't scared. And I don't know why, logically. I don't know why I wasn't struggling with a lot of anxiety. I don't know. There was just this inner sense, that things were going to get treated quite quickly. And, I mean, I had 2 surgeons because-- I don't know what the procedure is like in other countries, but in the UK, the treatment plan was a sandwich of chemotherapy and esophagectomy, and then chemotherapy at the end of that. The esophagectomy is the critical bit because the surgery essentially-- mine was actually an advanced tumor, so it had been there a while. So I knew surgery was the best course of action because this thing had been growing inside of me. And it was like-- it's a drastic surgery, the esophagectomy, because they're obviously removing a chunk of your esophagus, and you're also having essentially a gastric band. I was massively into fitness before I had cancer, so it almost sounds slightly annoying now, but the challenge now is more to focus on getting the calories in. And maintaining good weight is the focus. But that said, I think it was just a lot of-- I was having to process a lot of information because the treatment was coming at me quite quickly. And there was things about it lifestyle-wise that-- because prior to chemotherapy, I was on a feeding tube to get my nutrition. And at the time, I was more concerned that I wouldn't be able to eat in the normal way, that I'd maybe end up long-term on a feeding tube, which was something that was-- you've got all these questions about what your future and your lifestyle looks like post-esophagus cancer, and that was kind of in the mix.

But I think one of the things that was amazing was I had a lot of community, I had a lot of support around me in Manchester. So I was really fortunate, even though there were some wards within the local hospital I was in that were COVID-restricted still in terms of visitors, they made allowance for me to be able to have visitors and stuff like that. So I was really fortunate and even had a friend that worked in the hospital that would come and see me at the end of her shifts and stuff like that. So I had a lot of people checking in when I was in hospital, so I felt very supported through that process. But the thing that's complicated is you're very unwell and you're having to take in lots of information in terms of your treatment plan. And then they can't give you guaranteed scenarios of what your lifestyle is going to look like at the end of surgery. So that's the grey area, really. Yeah.

Dr. Frank Penedo: Sure, Rachael. And cancer in itself, it can be very challenging, let alone during a pandemic, when we have to adjust so many other aspects of our life. But it sounds like you had a pretty good support system, which, as we know, helps our cancer patients and survivors really manage the experience and get through. You touched a little bit upon your treatment. You mentioned it included surgery and reshaping of your esophagus and the stomach. And you touch upon the effects of surgery, which can be persistent. It can really persist well beyond that active treatment period. Can you talk a little bit more about how you've been able to cope with these side effects and changes that you've experienced?

Rachael Kearney: Yeah, so I was a massive foodie before all of this, very food-orientated. Food was almost, in family and friendship circles, a love language. And Manchester's got a thriving food scene out in the city and stuff, so a lot of socializing revolved around food. And I think the great thing about the upper GI ward that I was on at the time is there's no secrets and there's no sugar coating everything. They give you probably sometimes worst-case scenarios in terms of what things might look like after surgery. But the one thing they did say is I would need to have a puree diet moving forward and that would, to all intents and purposes, be permanent as a lifestyle change. They did say I could have these particular-- they're a bit invasive, but dilatation procedures where there's a physical stretching of the esophagus-- what actually happens is if-- once you come out of the surgery and you try to eat food, what's actually happening is things sometimes get caught. So I've got to be really careful about what I eat. I'm now on basically a liquid diet. And for texture, there's certain types of crisps, or, obviously, you guys say chips, that are melty or crackers that are melty in texture. So at least I get some kind of crunch just in terms of what I'm putting into my mouth and stuff. But I'm pretty much living on blended food or soups and ice cream and yogurt and things like that and smoothies. So the diet is massively limited now in terms of what I eat. The dilatations were offered to me as a way to kind of stretch my esophagus to encourage-- it's the swallow that's the challenge.

So if I had something bread-based and tried to eat that, it just gets caught and it just comes straight back up. So I live alone. So I don't try and test the boundaries of what I can eat and what I can't eat because I don't want to risk choking and things like that when I'm at home on my own. And then obviously, in public, there's so little warning if something needs to come back up. Socially, it's just a no-no. So what I have found, 2 things, are, I guess, really making my needs known. So there's a food market in Manchester I went to at the weekend. And there's this amazing Mexican vendor there. And they make things that are not on the menu for me that pureed, amazing, delicious Mexican food that-- they just know what my condition is. And I'm really clear I've had esophagus cancer, and this is the situation.

And then I think the other thing that's really key for me, because when I tell people I'm never going to be able to have pizza again in my life, people look at you and feel really sad because food is such a thing that brings joy. And I was so food-orientated before all of this. But I think I have to keep remembering I was on a feeding tube for 3 and a half months and I wasn't sure if that was going to be my new normal moving forwards. And there's obviously people, even young people, with other medical conditions-- I found these people on social media who live permanently on a feeding tube. Lifestyle-wise, that is so limiting. And I just thought, "Actually, my lifestyle-- it's changed. But I'm still out, I'm still active." I used to throw around kettlebells a lot, but now I'm just doing a lot of walking. So I'm still walking a lot and getting my exercise in. It's just that my diet has gone more simplified, this liquid diet, and I'm grateful that I can taste things and still occasionally have a cocktail. And obviously, the volume of what I can tolerate because of the gastric band side of things is just less in terms of volume. So I just get fuller quickly, as well, just being mindful of that.

Dr. Frank Penedo: Rachael, thank you for sharing that experience. I think we tend to undermine or underestimate what happens after treatment. We're so focused on curing the cancer and having the right level of treatment and getting the best care possible. But you have so eloquently described what experiences one can face after treatment. And these can be very challenging for anyone. Was there anything that surprised you? Were you expecting these changes or anything that popped up that said, "Oh, I wasn't thinking this was going to be my experience after being treated?"

Rachael Kearney: I did surprise myself at how well, relatively speaking, I coped with the puree diet. I think I thought that was going to affect my mood. The weird thing about my journey that I've shared with Call On Courage and just my story in general is I had 3 difficult years all truncated together. So before I got my esophagus cancer diagnosis, I've had burnout because I've been part of a startup that was a bit bonkers and been working excessive hours and stuff like that. So because I've gone from burnout to then going into this physical illness, from mental health to physical illness, and then coming out the other side of that, I was thinking, "Is this going to really be a setback in terms of mental health journey?" And amazingly, it wasn't. And I think there was things that had been put in place in my life from the burnout that was like support networks and things-- I'm very creative, so things creatively speaking that I put into my lifestyle that I thought just really bolstered my mental health and kind of allowed me to recognize there was a purpose in this quite messy journey. Obviously, the surprise was, "Oh my gosh, I'm living off soup a lot and blended curries and things like that and everything." My blender gets used all the time, but I've also been quite determined to try and not hibernate or not massively change my social life. I've had to adapt my social life. And in the past, it would be a 3-course meal and a bottle of wine. Wouldn't think anything of it. But these days, it's just literally 1 course. It's either pudding or something savory that someone's blended if I can go out and get that, and then 1 glass of alcohol, and then I'm full.

And I'm having to get in the habit of eating little and often. And I don't experience hunger. That's another sort of side effect. There's weird things about it because I don't experience hunger. It has become quite liberating because I've not got food on the brain. I'm not thinking about my next meal or-- I recognize the old version of Rachael was having to work a busy job, and then there was a lot of preparation around food and cooking from scratch and going to the shops and all of that kind of stuff. And everything's so much more simplified now in terms of what I purchase, whether it's ingredients or premade stuff. And it's quicker, and I'm literally just getting the nutrition in. There's still a pleasure to eating certain types of food, but that emotional connection to food has totally gone. And just the hunger isn't there. I've probably got to be a little bit more careful because I get a lot of steps in in a day because I'm active, that I should take snacks with me just because, even not having hunger, suddenly, I can be a bit-- not dizzy but light-headed. And that's when I recognize my blood sugar's low, and I need to kind of get something in to kind of give me energy. But yeah, the surprise would be, I guess, how liberating not having hunger is. And it's one less thing to think about, even though people listening to this, if you love food, that will be hard to wrap your head around because I understand that because I think it's such a big part of our social life and how we express ourselves.

Dr. Frank Penedo: Rachael, I mean, it sounds like you've been coping remarkably well. And I think it's not-- shouldn't be very surprising to all of us that most cancer patients actually do very well. It's a normal fear, concern, anxiety surrounding the diagnosis and treatment. But most of them adjust really well, making these changes and adaptations as needed so that they can manage treatment-related challenges, limitations that are going to persist over time. Anything that you would advise for cancer survivors and patients on coping with cancer?

Rachael Kearney: My 2 big things, I would say, that change stuff is community and purpose. And I think it's an obvious thing to say, but it's not going into that sort of tunnel mental health-wise around like, "Why me?" Because cancer is so indiscriminate, and the statistics we see on TV in the UK is 1 in 2 of us will have cancer at some point in our lifetime. It's obviously just more of a surprise when it happens when you're younger. But I'm massively grateful because there's a very special treatment center in the UK called the Christie, so that's where you go and have chemotherapy. And I was sat in the waiting room one time in the Christie, and there was just a very smartly dressed gentleman probably in his 70s. And I was asking which doctor he was waiting to see, and it was the same one as mine. And it turned out that he had exactly the same cancer as me. But when we spoke about what his treatment was, he was told he had about 6 weeks to live. Esophagus cancer is an aggressive cancer and I'm just-- honestly, there's not a day that goes by that I don't give thanks because the gratitude side of things is it was actually treatable even though it was advanced, and they were able to remove it. So I'm hugely thankful for that. And I know there's going to be people listening to this at all different stages of their cancer journey and different outcomes, but I think the community side of things for me was actually having friends that were like family that kind of swept in in Manchester that would come and visit me. I mean, come and visit me when my hair was falling out, when I was looking a mess. It was sort of important that people saw me at all different stages when I had the feeding tube in and post-surgery and stuff like that. But, yeah, I was massively grateful for that community.

So I think being part of some kind of community or being open with friends around where you are and what you need-- and sometimes, you need privacy as well as that. But yeah, I think connecting with people and seeing people when you're unwell is important to process stuff with people.

Dr. Frank Penedo: Absolutely. You touch on so many words that resonate with me as a behavioral scientist. We know social support and community is just critical to helping individuals navigate through a cancer diagnosis and survivorship. Social support is one of the strongest predictors of quality of life, for example. So having that sense of community support is really critical, and it sounds like you had that available for you. Also, having faith in the treatment you're getting and your treatment team is critically important because that's going to empower you to understand and believe that you're going to be able to challenge this and fight it and get better. You talked also about sense of purpose and sense of purpose and gratitude. And sense of purpose is really important. And I want to talk a little bit about this website and podcast, Call On Courage, which I love the name. So we know that cancer can be a devastating experience to many, and having courage is really a word that I use to describe many of the cancer patients and survivors that I work with, that I interact with. Can you tell us a little bit about this Call On Courage project and what your goals were?

Rachael Kearney: Yeah. Oh, absolutely. It's been something-- I actually started it prior to having cancer. So I started Call On Courage and the website CallOnCourage.com that started when I had burnout because I was really-- I've been basically part of something, a business venture that was faith-based. And I kind of thought that was something I was going to be part of for years and kind of do it with excellence and really go for it. And so when I did have burnout, it was just devastating to really let go of that because, yeah, I thought that was part of kind of what my future career would be attached to. So Call On Courage started initially just as a blog. I was just writing to kind of process some of those feelings and work through some of the sort of things that I felt. It sounds like a strong word because it was a work venture, but a sense of grief, a sense of loss to do with not being able to sustain in the business. So writing and blogging was just something that helped me navigate those feelings. And then I just recognized I ended up-- if I'm honest with you, I deleted a lot of those posts because I guess they felt like quite journal-like in their quality. And I thought, you know what? I want to create something that's a platform and a conversation starter about other people. There's so many other people out there that have got stories about having to start over or they've tried something, they failed, it's not gone in the way that they thought it would go. And so creating Call On Courage as a podcast, doing it as a podcast has definitely opened the door for just building friendships and connections across the world, basically with all different types of people that have done interesting things.

There's a woman that I'm still in regular contact with based in California. She knew at elementary school that she wanted to be a software engineer. She achieved that and then decided she hated it and then ended up having to do something totally different. There's another woman, Lu in LuLand, who's all about growing old outrageously. And she was in Portland and wore lots of fabulous outfits. And then she's moved to South London. And she's in touch with me now regularly as well. And, yeah, having a conversation with a guy, Mike Janda, who had a creative agency that serviced Hollywood and did $25 million worth of billings to creative clients. And we're having a conversation this afternoon. So I've not got a massive Instagram following or anything like that, but it's something very emotive about courage. And I think we've all got-- everyone's got some kind of story about grit and stamina and having to kind of dig deep to make harder things happen, whether that's health or career or whatever it is. But I'm particularly interested in that connection between creativity and courage together.

Dr. Frank Penedo: It is so important for other patients and survivors to hear a story from a survivor like yourself. It's relatable. It creates a sense of commonality, understanding that they're not alone and relating to experiences that you've faced, even if they have a different type of cancer, because some of these challenges are very universal across different cancers. And let me again thank you for sharing your personal story, which is very powerful. How do you think hearing your story can help someone cope with a challenge like a cancer diagnosis?

Rachael Kearney: Hearing my story?

Dr. Frank Penedo: Yeah, your personal story.

Rachael Kearney: I mean, my type of cancer is rare. So I was finding when I was googling-- I mean, it's not the best thing to do when you instantly get a diagnosis, but I was googling esophageal cancer. And the stats around it on Google aren't great. Yeah. It wasn't great when I was unwell to look at that, but it took a long time to get to actual sort of stories or testimonials around how people recovered from esophagus cancer. And so I felt a bit like one of the reasons-- and this is why I've written a piece for Cancer.Net as well. It was important to write about my story, was that at least there's a few more websites that have featured kind of what I talk about is my journey, what's been positive about recovering from esophagus cancer, because I was really struggling to find those particular stories online. And it was skewed-- well, the data around esophagus cancer is skewed way more towards much older people over 65, heavy smokers, drinkers, and more men that have this illness. But I mean, I also want to give sort of grace for the fact that every type of cancer is different, and even just speaking to people that have had breast cancer or ovarian cancer or whatever that is, or even a benign tumor that might have grown somewhere else, it's so case-by-case specific that I wouldn't be in a position kind of to dish out advice to say, "Oh, everything is going to be fine once you get your diagnosis. And it's about do these 3 steps towards gratitude and a creative project and X, and everything's going to be peachy." I really wouldn't patronize people with that information because I think you have good days and you have bad days with it. And it is definitely a journey of processing it through. I think me personally, I found my faith in my prior life really kind of bolstered things as well when I was processing things on my own that I wasn't kind of totally alone in working that stuff through. But I just think, yeah, kind of going back to the original point, I think it was just really practically important to kind of get a bit more content out there about esophagus cancer that's coming from a younger perspective and from a female perspective, because I think that was something that I found hard to research on when I was looking.

Dr. Frank Penedo: It's certainly a challenge, Rachael, for many providers, because there's a lot of resources for breast cancer, for example, prostate cancer, but the less common, more rare cancers, we still haven't done a great job of getting the word out there and creating the necessary support services. So I cannot over-emphasize how important it is to hear a personal story like yours to help these survivors. Just a few words in closing, Rachael, what advice do you-- what advice do you have for other people with cancer and survivors who are interested in sharing their story?

Rachael Kearney: Yeah, I think even just writing down what's happened for yourself is really critical. I think you don't have to necessarily get your story out on a blog. I was nowhere near that headspace as I was going through my treatment or illness or anything like that. But writing definitely kind of helped me process some of those feelings and the difficulty of it. I think if you're in a position to be able to-- I mean, I'm quite fortunate that I come from that background of building websites and creating stuff for myself, and I'm quite used to doing that. But I think if you can do it through a free platform or on social media and start to share your story when you're well, that's also a really great way of getting it out. But I've been really surprised and fortunate that I've approached places like Cancer.Net and, in the UK, Macmillan and some other cancer charities and cancer blogs and just asked, "Would you be interested in publishing my story?" And that's led to some great conversations like I'm potentially doing some press for another digestion charity in the UK that wants to talk about Christmas and the difficulties of someone like me living on a puree diet, kind of how you navigate holiday season or whatever with food.

So I've just found it's been a source of conversation starter and a sense of-- I'm in this interim phase between recovery, and I want to get back into work and stuff like that. And it's enabled me to kind of create things and pieces of work that I'm proud of. I'm in creative industries, so I can talk about that when I'm in job interviews and things like that as well. It kind of feeds into that, which has been wonderful. But I think you're in charge of your own story, and you don't have to overshare anything. So share as little or as much as you want about it. But I've definitely found there has been a response to it and, because I've shared with much bigger cancer organizations, that's also, on a very pragmatic level, that's increased a lot of traffic to CallOnCourage.com, and I'm seeing a lot more visitors from around the world. And the spread is kind of mixed a lot more. So I'm massively thankful for that because it's just wonderful that other people's stories are kind of getting out there as well through the blog.

Dr. Frank Penedo: Well, Rachael, I want to thank you for sharing your very remarkable and inspiring story with us today. Thank you for your time, and it was great having you.

Rachael Kearney: Oh, thank you so much, Frank. I've really enjoyed it.

ASCO: Thank you, Ms. Kearney and Dr. Penedo. You can find more stories from people with cancer at the Cancer.Net Blog, at www.cancer.net/blog.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

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The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net Podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today, we're going to be talking about what health equity and quality care mean in the context of cancer care and discuss highlights from the 2022 Quality Care Symposium in these areas. Our guests today are Dr. Fay Hlubocky and Dr. Manali Patel. Dr. Hlubocky is a licensed clinical health psychologist with an expertise in psychosocial oncology and a health care ethicist at the University of Chicago. She's also the Cancer.Net Associate Editor for Psychosocial Oncology. Thanks for joining us today, Dr. Hlubocky.

Dr. Fay Hlubocky: Thank you, Brielle. Hello, everyone. So wonderful to be with you all today.

Brielle Gregory Collins: Thank you so much. And Dr. Patel is an assistant professor at Stanford University in the division of oncology and a staff thoracic oncologist at the Veterans Affairs Palo Alto Health Care System. She's also the Cancer.Net Associate Editor for Health Equity. Thanks for joining us today, Dr. Patel.

Dr. Manali Patel: Of course. And thanks for hosting both me and Fay to discuss this really fun topic.

Brielle Gregory Collins: Of course, we're looking forward to it. Before we begin, we should mention that Dr. Hlubocky and Dr. Patel do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. So to start, Dr. Patel, can you first describe what the term health equity means and how it relates to cancer care?

Dr. Patel: Great question. Nice one to start off this podcast. So I think we've always been really focused on health disparities. So I love that you've asked, what is health equity? Health equity is really reframing disparities or differences in cancer outcomes with more of a justice lens. And the full definition, which I love from the Robert Wood Johnson Foundation, describes health equity as meaning that everyone has a fair and just opportunity to be as healthy as possible. This means that you remove obstacles that may impede people's ability to attain their highest health, such as poverty, discrimination, and the consequences of such powerlessness, lack of access to good jobs, having fair pay, quality education and housing, safe environments, and health care. And as it relates to cancer care, it means that everyone has a fair and just opportunity to be as healthy as possible, even with a cancer diagnosis. This means having a fair and just opportunity to receive all of the evidence-based care that we know makes a difference, as well as high quality care that matters from screening to the end of life.

Brielle Gregory Collins: Thank you so much for explaining that. And Dr. Hlubocky, talking about quality care, what does quality care mean in the context of cancer care?

Dr. Hlubocky: Thank you, Brielle. So according to the Institute of Medicine, now known as the National Academy of Medicine, quality care requires the safety, the efficacy, and the efficiency of care delivery. It's also timeliness and a patient-centered approach that's coordinated by an inter-professional oncology team with the integration of evidence-based or research-based practices to continually improve cancer care. It's a very comprehensive, a very value-based form of care that adheres to evidence-based guidelines. It assures the treatment of symptoms, and the side effects of cancer, and the cancer treatment. And it's also coordinated care with strong communication amongst all clinicians and patients, which might involve a written care plan that details all of cancer care, the care in a clinical trial, if that's a potential option for patients. And it also involves shared decision-making, including honest and frank discussion about prognosis, the intensive therapy, patient's values, and also preferences regarding care. As well, it's a research-based support for psychosocial needs. It provides palliative care throughout the course of treatment from diagnosis through the end of life, and end of life care involving hospice.

So quality cancer care was first coined by Dr. Joseph Simone, who was a pediatric oncologist and was the first, really, to advocate for quality-based cancer programs in pediatric oncology for both leukemia and lymphoma. And he was the one who truly started this movement that involves centering on every patient with cancer and every care program. So this year in Chicago at the Quality Care meeting, these interdisciplinary experts really highlighted the latest quality improvement research, as well as guidelines that helps us to improve the quality of cancer care from diagnosis through treatment to survivorship, and again, through end of life care.

Brielle Gregory Collins: Great. Thank you so much for walking through that. And yeah, we're excited to discuss more research from the Quality Care Symposium, too, a little later in this podcast. Dr. Patel, we know that health equity and quality care are linked. So how do health equity and quality care relate to better overall cancer care?

Dr. Patel: Great question. I love the fact that you brought up the Institute of Medicine's definition of quality because in my mind, doing work in health equity for over a decade now, really looking at health equity and quality, I've always thought of them as being intricately linked. But what I loved about the ASCO symposium and now some of the word choices that we're using, really does think that equity is not just a single component of quality, which previously it was. And now, the Institute of Medicine moved equity into being more of a cross-cutting dimension where it is an underpinning of all aspects of what Fay just outlined, in terms of effectiveness, safety, timeliness of care, etc. I think equity, in order to actually achieve high quality care, especially in the cancer realm, health equity has to be a fundamental component of such care. And so now, I'm going to take a step back because I think for years, we've been looking at equity as more of an issue of just access. But you heard in Fay's definition, and the definitions that are out there, that exist for quality, that equity and quality are not really just about access. In other words, differences in cancer care and inequity in cancer care is due to the fact that some populations, such as racial and ethnic minorities, for example, have poorer access to care than others. That is true, but this is just one factor, and it's not the only factor. Even when access is equal, we know that some populations tend to receive lower quality cancer care than others, be it by race and ethnicity, be it by socioeconomic status, gender identity and sexual orientation, or even age. So really, equal access does not equate to equitable care.

What's nice about linking quality and equity and this intricate linkage of the 2 means that you're addressing the effectiveness of the care. You're ensuring that, when you think of quality in terms of equity, the outcomes you're thinking about in terms of race and ethnicity and actually moving towards considering, for example, what different things mean to different patients in terms of effectiveness, safety, timeliness of care, and ensuring that not only are people receiving the care, but that they're all receiving high quality care. I hope that makes sense.

Brielle Gregory Collins: It absolutely does, and I appreciate you, again, walking through that and just explaining how those 2 are connected. And I want to go into some of the research that was presented at this year's Quality Care Symposium. So Dr. Hlubocky, can you introduce some of the key studies or themes that came out of this year's symposium that addressed quality care?

Dr. Hlubocky: Thank you. Absolutely. There were several key quality cancer care themes that had to illuminate the cutting-edge research that is being conducted today and the advances by noted experts in the field, specifically at the symposium. The first being financial toxicity, or financial hardship, and problems that patients may encounter that's caused by the cost of treatment. This was identified as a major thematic session, where multidimensional approaches to addressing financial toxicity were presented, things like screening interventions, survivorship advocacy, and policy. Additional interventions to address financial toxicity were presented. And Dr. Ezekiel Emanuel, from the University of Penn, he's Vice Chair of Global Affairs, but a well-known ethicist in the country. He actually launched the meeting with a phenomenal keynote that was entitled, "New Directions for Cancer Care in the U.S.: Building a Transformational Research and Development Ecosystem and Healthy Payment Landscape That Better Supports Our Patients." We then heard about how screening tools add value to identify patients with financial hardship and how to best implement them. We learned what other cancer centers have implemented regarding financial toxicity programs, and how any cancer center or any practice can implement these tools and interventions aimed at helping our patients with financial toxicity or hardship.

Additionally, smart solutions like leveraging digital health tools to improve cancer care delivery, this also included a study on how health technology can be utilized to improve the delivery of cancer care today and the future, which evaluated the use of web versus mobile devices for ePRO reporting [electronic patient-reported outcomes reporting] and severe symptom responses. I believe it was 6 cancer centers. Symptom monitoring and what we refer to as patient-reported outcomes was also a key topic. And we heard about severe symptom reporting in medical oncology patients at a community center that was assessed through a platform, as well as severe symptom reporting and surgical patients assessed through an EHR-integrated ePRO questionnaire, again, at 6 centers by Dr. Wong at Dartmouth. Physical impairment, pain, and fatigue were top concerns that were identified, and Dr. Wong and her team also identified predictors of severe symptoms so that population surveillance should be considered a priority. And she also encouraged that interventions are really needed to address common severe symptoms and that these future studies should define what is the most effective migration strategies for these symptoms.

Successful integration of health care and health services research interventions in oncology was also another thematic session, and it offered a framework for leveraging health care services research to improve cancer care delivery across the diverse populations. And we know that leaders in the field discussed a variety of these interventions, including hospital at home and geriatric assessment. For example, guidance and geriatric assessment and clinical practice was also presented by the former Cancer.Net geriatrics editor, Dr. William Dale, which included a need to use to inform treatment decisions which would systematically change cancer care delivery.

And finally, an interactive roundtable on rethinking advanced care planning was also held here. These panel experts examined the current model of advanced care planning. What is the merits? How can it be reimagined? And how do we measure outcomes and tools, and what is the impact on caregivers? And finally, regarding the smart solutions, leveraging the digital health tools, we looked at big-tech solutions to common care delivery obstacles, leveraging electronic health records to support treatment and achieving equitable screening. Especially, for example, lung cancer was discussed. I think that hit most of the studies that were presented. What do you think, Manali? Did I miss anything?

Dr. Patel: You did a really nice job of highlighting all of them. There were so many exciting studies that were presented, and it was really a fun meeting not only to spend time with you, Fay, but then also to meet up with colleagues and to see the cross-cutting research across both equity and quality, and the linkage between the 2. On that note, I think I can talk about the different ones that were kind of more focused on equity. And the opening theme was a really nice theme about the structural barriers to equitable care delivery. And again, when you think about quality and equity as being intricately linked, if people are unable to get the highest evidence-based care, providing care-- we can provide care, but if it's not evidence-based care, then are you really moving the quality needle forward? And so the opening theme really looked at, I think, reframing and shifting our views of the focus on the patient as the reason for disparities and inequities to really thinking about structural barriers and barriers that may exist not only at the policy level, but also barriers that exist just in the way that our system is set up with structural racism, ways to overcome structural racism through system-level changes.

Another theme that I thought was really nice that was highlighted was the impact of social determinants and complications from social determinants of health on being able to achieve the highest quality of cancer care for patient populations. And a lot of studies looked at associations of the impact of housing and other health-related social needs such as transportation aspects, which we all know are a clear indicator and a clear barrier for some in terms of being able to achieve the highest quality care. We also saw a lot of abstracts both in the poster discussion, as well as in the main plenary session, including Dr. Otis Brawley's presentation that talked about this very question really here that you're asking us, which is about the linkage between quality and equity. And that entire plenary session that I would love for others to go back and to listen to had some very key poignant takeaways about the linkage, and how that has changed and morphed over time, and also, how our view of equity and this intricate linkage-- again, I know I keep saying intricate linkage, but that's because that's what it is. But this component being more of an underpinning, looking at quality from a whole, from the lens of equity, he did a really nice job of shedding light on this topic.

Brielle Gregory Collins: And Dr. Patel, I do want to ask one follow-up question. So you mentioned this term, social determinants of health. Can you just briefly describe for our audience what that term means?

Dr. Patel: Yeah, very good question. And I think there's a lot being done at ASCO, but also at the national level. And the social determinants of health are these structures that are set up within the way that our social system is set up. So things like housing, transportation, food. Interpersonal violence, for example, is one kind of health-related social need that can come out of not having access. But these are the social structures that are set up that determine how healthy you can be. So if you take a step back and you think about cancer care, for example, and you look at individuals that may not have a home and may have homelessness, and you think about how our treatments may impact. So many of our treatments may cause people's white blood counts to lower during periods of their treatment where we hope they aren't living in congregated areas such as homeless shelters, for example, where they can then become really infected with what we call opportunistic or other infections during treatment. How the homelessness situation impacts someone's health. We know that it not only impacts their ability to receive and our ability, as clinicians, to provide the highest evidence care for individuals living in those situations, but it also impacts other health. And we know that homelessness really does impact an ability for one to be able to be as healthy as possible.

The same with food. We know that the pandemic and some of the work that we've done, Fay and I together, as well as others, have looked at the impact of the pandemic on food insecurity. Now, food insecurity has been a large issue for people, and a determinant of health is what I call it, a social determinant of health. But we know that food is medicine, and for people during the pandemic, we saw food insecurity significantly rise due to wage loss, due to other issues regarding income loss. And that then led to being unable to be able to eat as healthily as possible. If you don't have access to the right food, we know that that makes a difference in terms of your ability to make it through particular cancer treatments. For example, if you're unable to get enough magnesium, calcium, potassium, that can influence what we call your electrolytes and your labs, and make it very difficult for us to give treatment. But even prior to a cancer diagnosis, we know that food determines how healthy you are. And if you're unable to attain food sustenance even from an early age, that can really lower your ability - if you go back to the definition of health equity - your ability to be as healthy as possible.

And these social structures then, which I loved about the ASCO Meeting this year, is-- I've been going to the ASCO Quality Meeting for many years and have kind of been-- Fay knows, right? We've kind of been like these lone people out in our little group of people that come to the ASCO Meeting and the Quality Meeting. We all speak the same language, but there was a real emphasis on interventions this time around, and how can you overcome what, traditionally in the medical realm, we don't think of as being linked with health or at least in oncology? I think primary care physicians and pediatricians have been focused on this for many years. But for us, in oncology, it hasn't really been first and foremost as part of our problem that as oncologists, if we know that people cannot get to our clinic, we need to intervene on transportation. But these other issues like homelessness and food insecurity and poverty really are also in our realm as well in terms of impacting one's ability to achieve health equity.

Brielle Gregory Collins: Thank you so much. That's a really helpful explanation. And too, I want to get into-- there was all this great research to come out of quality, but I want to talk a little bit about what changes are happening in cancer care to improve health equity and quality care. So Dr. Hlubocky, we can start with you. Can you talk a little bit about some of the changes you're seeing happening in cancer care to improve health equity and quality care?

Dr. Hlubocky: Well, I love what Manali has said about coming together first as a community at the meeting, where we're not just friends and colleagues, but we're collaborators and mentors to one another, and we are stimulated by one another's presentations to truly design research that optimizes care for every patient everywhere. And I think that's now the priority in that. And it's important to learn about some of the best practices that can help clinicians really reshape strategies and make key decisions to improve, as we said, that quality, that safety, and the efficiency of cancer care delivery. Certainly at ASCO, we're doing quite a bit with the QOPI Initiatives, the Quality Practice Initiatives, where every cancer center or practice has access to measures that are evidence-based, so we can identify what are the key symptom issues that patients are experiencing so we can use these measures. And ASCO has really been a wonderful partner for many practices along the way. So it's really, really seeing this research is such a motivator. And I wonder, Manali, what additional highlights stick in your mind as to what is the future when it comes to cancer care?

Dr. Patel: Yeah. I mean, that's a fantastic question. I love this question, Brielle, that you're asking us to reflect on. As I mentioned, I really do think that there's been a real shift. And sadly, I think it took George Floyd's murder to link us to the huge discourse. Now that's happening not only in our own small circles locally, but also at the national and policy level, that equity, more so than I've ever seen at a meeting, even at our annual meetings in ASCO, has really become the forefront. And I've started to see meaningful change of not just talking about equity, but also thinking about interventions. I certainly, we think that we're seeing more discussion about equity, more awareness of the importance of equity. The question that you just asked about social determinants of health now is now part of our vernacular and our lingo now, which is wonderful, that we don't always have to describe the impact that social structures and our systems set up for us to be either healthy or not. But what we're also seeing are more dollars being put into incorporating equity, not just research dollars. I think what we saw at the ASCO Quality Meeting was there's a lot of research in this area and there are a lot of like-minded folks that are collaborating together to try to overcome this. But there are also programmatic dollars. And I think even within ASCO and within other organizations that are traditionally medically focused, there's a highlight of equity as part of the mission statement now, which is hugely different than where we were just a couple of years ago when both Fay and I were on the Health Equity Committee, that was not part of the mission statement. So the fact that that's being applied in a visual statement is really different.

We're also seeing policies being made both at the local level. For example, in California, lots of policies being made for MediCal organization.  We're starting to see more of a reflection of inequities in care and really, interventions to try to move that on the ground, both within clinics reporting on data, like Fay mentioned, I think is extremely important. A basic step, yes, but one that just has not-- it's been lacking. We conducted a project that was led by Lori Pierce and others through ASCO that looked at just who are the people that are coming into your center? And how many are being enrolled on clinical trials? And what are the race and ethnicity and income and social status of these individuals? And many centers just are unable to report that because we don't collect data on it.

So Fay mentioned that something that does seem very basic now is becoming part of the fabric and there's now more understanding as to why these things are important, and why we need to measure them. And what are we going to do about it? So I really like that there's research happening in parallel where, again, as I mentioned, there were a lot of abstracts that were focused on the association of housing. But at the same time, then you've got interventions that address housing. People that are working with housing authority, or even at the VA, for example, creating safe housing for people during treatment. It doesn't address the whole issue of homelessness, but it does try to band-aid the situation until we have national policy that can provide better housing for individuals overall, or to address some of these issues. And I think that it's been really refreshing-- I don't know about you, Fay, but just for me, refreshing to see interventions that are solution-focused. And what can we take away from these abstracts and really try to implement at home? Or what are some novel ideas that we can do to overcome some of these issues? I hate being stuck in the description paradox of disparities, disparities, inequity, but no real solution as to what we can try to do at home.

Dr. Hlubocky: I fully 100% agree with Manali's statement right there.

Brielle Gregory Collins: Absolutely. And it's so exciting to hear about improvements being made and the needle being moved forward in these areas. I'm sure it's very reassuring for patients to hear that. And speaking of that, there's so much information in this area. For both of you, where do you recommend patients can go online to learn a little bit more about health equity and quality care?

Dr. Hlubocky: Yeah. First and foremost, Cancer.Net. Of course, we have such wonderful content associated with many of the topics that we discussed today, such as financial toxicity, and various symptoms, and psychosocial issues, depression, anxiety, palliative care, end-of-life care. So that's definitely the first stop. As well as the American Cancer Society would be the next one. And the National Coalition for Cancer Survivorship. And of course, the National Cancer Institute, which centers-- they all center on quality care issues, such as those we just discussed today. And of course, I don't know about you, Manali, but really talking also to your cancer team. So that's the first step. But really, I think so many patients are fearful to address some of these issues with the team, [and think that] that we don't have time, and we make time. We make time. Our patients are very important to us, and we really want to optimize care the best that you can. So if any of these issues are a burden and barriers to getting the best care, please reach out to us. There are financial navigators, there's palliative care clinicians, psychosocial clinicians, and many cancer centers, as well as some practices in that. So talking to your oncologist, talking to your nurse practitioner, and they are great resources as the first step to attaining care after you've read some of these resources. Are there others that come to your mind, Manali?

Dr. Patel: Yeah. I mean, great question. I love how you brought it back to the local teams. In terms of thinking about resources, I agree, there are a lot of resources that are local. And so ask your clinical teams, but then also other patient advocacy groups may have more information about resources to overcome some of the barriers that some patients are having, particular barriers, just to get general information about health equity. As Fay mentioned, we love Cancer.Net. I mean, I think it's one of the best resources that I've seen. In fact, my mother and my father go to the website pretty often. They are both cancer survivors as well. But there's a nice piece, again, about health equity and how it integrates into all facets of care and all facets of one's journey through cancer. I think, as I mentioned before, the Robert Wood Johnson Foundation really has nice resources on health equity and also other web-based portals that you can delve into. So there's as much information as you want to learn about health equity, and also solutions focused more on the general picture that's maybe not related to cancer, but again, is linked to cancer. The American Public Health Association is also another really nice website that has a broad swath of how health equity and the issues that we talked about today, the social and economic structures, impact one's health overall. Again, not cancer-related, but everything is cancer-related. And so you can bring back some of those take-home messages to how it may impact one's cancer care.

And then I really love-- for me, personally, the University of California Berkeley is a nice, free resource that has publications, depending on how deeply you want to delve into the questions and some of the brief topics that we've talked here, that are all focused on health equity. And it's a really nice website that hopefully, we can put into the link of the podcast description.

Brielle Gregory Collins: Absolutely. Those are great resources. Thank you both for sharing those. And thank you again for your time and for sharing your expertise today. This was such a great discussion. It was really great having you both.

Dr. Patel: Well, thank you for even highlighting this important topic of health equity and quality. Again, for me, it seems just completely, almost a no-brainer, that these 2 go together. But it's not always as easy as you think to link the 2. And so it's really nice that you all have come up with this podcast idea and also brought wonderful Fay and me together to do this. [laughter] There's so much admiration for what Fay is doing, and it was really humbling to be on a podcast with you, Fay.

Dr. Hlubocky: Oh, it's an honor and a pleasure to be with you, Manali. You truly are an advocate and a guru, a wisdom when it comes to equity and equity issues and illuminating the issues nationally. So such an honor and pleasure to be with you. And of course, with Claire and Brielle, and to all the patients and caregivers and our colleagues, we're here for you. So don't forget to reach out to your oncology team and here with us at Cancer.Net.

Brielle Gregory Collins: Thank you both so much.

ASCO: Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Xiuning Le discusses new research on targeted therapy for non-small cell lung cancer presented at the 2022 North America Conference on Lung Cancer, held September 23-25 in Chicago, Illinois.

Dr. Le is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas. She is also a 2022 Lung Cancer Advisory Panelist on the Cancer.Net Editorial Board.

You can view Dr. Le's disclosures at Cancer.Net.

Dr. Le: Hi everyone. This is Xiuning Le. I'm an assistant professor here at MD Anderson in the Department of Thoracic/Head and Neck Medical Oncology department. I am a medical oncologist. I am a clinical investigator and also translational researcher. So today is a great opportunity to discuss some of the new meeting updates from 2022 North America Conference on Lung Cancer. Let me begin with the information about the meeting itself. So this conference, North America Conference on Lung Cancer, is organized by an organization called the International Association for the Study of Lung Cancer. As reflected in the name, this is an international organization for all the lung cancer researchers to get together to share our research, experience, and also patient advocates as well as patients participate in this fantastic organization. This organization also has meetings every year, including a World Lung Conference as well as the meeting we're going to talk a little bit about today, focusing on the progress we made in the North America. Therefore, it's called North America Conference on Lung Cancer. In this year's meeting, we had a very active agenda with multiple presenters from different parts of the U.S. And we also had international participants as well. We had exciting updates on some of the targeted therapy trials as well as updates from immunotherapy trials. So it was a very productive meeting.

Let me start with some of the updates from the targeted therapy space. During the meeting oral presentation, there were 3 abstracts selected for oral presentations. The first talk I would briefly discuss today is an update study for ADAURA trial using osimertinib as an adjuvant therapy for resected lung cancer patients whose tumor has EGFR mutation. This was presented by Dr. Roy Herbst, key investigator on the trial from Yale Cancer Center. So ADAURA trial is a multicenter international trial taking patients whose lung cancer have EGFR classical mutation at the diagnosis, or stage 1B to 3A, and then undergoing chemotherapy as the initial adjuvant treatment. But after completion of those treatments, patients were offered opportunities to go on to the trial receiving either osimertinib for 3 years or best supportive care placebo. The primary report of this trial became available in year 2021, where the osimertinib-treated patient had a significant clinical benefit reflected as the disease-free survival was much higher in the patient population who received osimertinib. The results of the ADAURA trial led to the FDA approval of using osimertinib in the surgically resected EGFR-mutant non-small cell lung cancer. So that's the background of this year's update and presentation.

Now, in the fall of 2022, after additional long follow-up, the data become more mature because although we still don't have overall survival results, we start to have 3-year disease-free survival. So in the study population, each is over 300 patients each arm, the 3-year disease-free survival rate was 84% for patients who receive osimertinib and then for placebo group is 34%. As you can see, this is a 2.5-fold significant benefit in the patient who received the treatment. The presentation was also a breakdown the patient population by their stage by different subgroup analysis across the board. The patient who received osimertinib derived benefit and then the hazard ratio remained to be between 0.2 to 0.3, depending which population we're looking at. Really, this data validated and confirmed the prior knowledge of this approach of offering adjuvant osimertinib really works and really should be offered to every single patient who qualifies for this study. One update on the subgroup analysis is the benefit for preventing brain metastasis to happen in the patients. Very impressive. We observe a hazard ratio of 0.24, meaning that if a patient goes on to osimertinib has a 4-fold benefit of not to develop brain metastasis. Overall, the conclusion of this presentation is that this data becoming more mature, and then the mature data reinforced that adjuvant osimertinib really should be the standard of care which we have been using pretty widely in the clinic.

The second abstract I want to talk about is a presentation that's presented by Dr. Lyudmila Bazhenova from University of California, San Diego. So she presented a pooled updated analysis on a novel EGFR exon 20 insertion medication. And then this medication currently is under U.S. FDA evaluation with breakthrough therapy designation. The drug's chemical name is called DZD9008, and then the drug's brand name is sunvozertinib. This is a great addition to the treatment option that we already start to see for EGFR exon 20 as a new inhibitor coming at the horizon. EGFR, we now start to classify all the mutations into classical mutation versus exon 20 mutation, as we are using different targeted therapy for different patients. For EGFR exon 20 insertion, we have already 2 FDA-approved drugs. One is amivantamab, the other is mobocertinib. But we still need more options for our patients. And this new medication, DZD9008, is having a great potential of becoming the next-generation EGFR exon 20 drug, as it showed good efficacy and pretty low toxicity.

So let's review the data that's presented here. In this meeting abstract, the authors combined 2 studies. One is called WU-KONG1. The other is called WU-KONG2. The first one was conducted in the U.S., and the second one was conducted in China. So there is a value of pooling different patient populations together and then not just getting the sample size greater but also understand different patient population, are they all having very similar benefit? Here the focus on analyzing the patient population that EGFR exon 20 lung cancer who have already received the chemotherapy. In the total of 71 patients analyzed here, in the subgroup of receiving 300 mg daily dose, the response rate was observed to be 40% to 45% depending on if you're using the central review system or you're using the investigator evaluation. But again, showing a very promising response. I want to put those numbers in the reference. For example, the currently FDA approved, the mobocertinib, in their population also had prior treatment. The response for mobocertinib was 28%. In the over 100 patient population, in these 71 patients, they see a 40% to 45% response. So potentially this one is having an even better efficacy really translate into clinic can be a great opportunity for the patients who had chemotherapy and needs something else. Also, we reviewed the toxicity profile. This drug is overall pretty well tolerated. We have to say that the population is relatively small. In order to truly understand toxicity, we usually want to look at the multi-hundred patients' experience, but I believe the data will mature over time. I would have to say the result here is very exciting.

The third abstract I will be talking about today is presented by myself, Xiuning Le from MD Anderson. In this abstract, we evaluated tepotinib, which is a MET inhibitor, their efficacy and safety in MET amplified non-small cell lung cancer patients. As we already know, MET exon 14 skipping represents a molecular subgroup that can benefit from MET TKI, including tepotinib. But MET amplification without MET exon 14 is another patient subgroup that could potentially benefit from MET inhibition. As in those cancers, MET not using exon 14 skipping as driving events rather than amplify. So the gene makes many copies of itself, so that drives the tumor growth that way. In this abstract, in this analysis, MET amplified non-small cell lung cancer patients were identified and offered tepotinib. So in this group, there are 24 patients who were treated on the VISION trial cohort B, and we observe a response rate of 42%. For a targeted therapy, having a 42% of response is really pretty encouraging. And the duration of response also is expected at multiple months. We showed that the therapy was particularly beneficial for patients who are treatment-naive. In that setting, the response rate can be as high as 70%.

This time, this year, we updated our molecular analysis for this patient cohort trying to understand deeper, do we have other signals to help us to decide which patient could benefit more and which patient might benefit less and then need something else? In the molecular analysis, we find that focal MET amplification is quite important. In another word, if MET amplification is the only event, then more likely this MET TKI will work in that patient population. However, if the tumor also has p53 or RB loss or certain other genetic alterations, then the response rate can be more inferior. So I think we are starting to understand each of the molecular-driven patient population group into even more molecular detail, understanding the co-mutations' impact to the clinical outcome. So I think this abstract is interesting in pointing directions of how to use an existing medication to patients to magnify the benefits that we can potentially achieve.

So this year's North America Lung Conference was really productive. We had a lot of stimulating presentations and a lot of discussions. Other than the targeted therapy session, we have seen 2 exciting abstract on the immunotherapy updates. Other than that, we start to have more opportunities to learn about cancer screening, cancer prevention, smoking addiction, and then the cancer survivorship. There are 2 abstracts presented at the oral section for that topic as well. So this meeting is particularly interesting opportunity for North America investigators, especially in their junior stage, to network, to present their work, and then to have exposure to major investigators in the field as well.

Dr. Le: Thank you, Dr. Le. You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Cancer.Net Editorial Board members discuss new research in gastrointestinal and genitourinary cancers presented at this year's ESMO Congress, held September 9-13 in Paris, France.

First, Dr. David Ilson discusses treatment advances in liver, colorectal, and gastric, or stomach, cancers. Dr. Ilson is an attending physician and member at Memorial Sloan Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College.

You can view Dr. Ilson's disclosures at Cancer.Net.

Dr. Ilson: Hi, I'm Dr. David Ilson from Memorial Sloan Kettering Cancer Center in New York. I'm a GI medical oncologist, and it's my pleasure today to review some important presentations in GI cancers from the recent ESMO meeting in Paris from 2022. I have no relevant relationships to disclose for this discussion. So, important presentations were made in hepatocellular cancer, in colorectal cancer, and gastric and other cancers, and I'm going to highlight some of the key presentations from the meeting. 

One of the most anxiously awaited presentations was one in hepatocellular or liver cancer. For patients that have advanced disease who are not candidates for surgery or local treatments, standard therapy now, it used to be lenvatinib and sorafenib, and that's now been replaced by the combination of an immunotherapy drug, atezolizumab combined with the drug bevacizumab. That's the new standard of care. And recently, we had a promising data for another immunotherapy combination using the drug durvalumab combined with tremelimumab.

So what we saw this year was another important global study looking at the first-line use of immunotherapy in hepatocellular cancer. This trial took 794 patients with advanced hepatocellular cancer and assigned them to a standard treatment with a drug called lenvatinib. Lenvatinib and sorafenib were the old standard treatments for hepatocellular cancer. And lenvatinib alone was compared to a combination of lenvatinib and pembrolizumab, an immunotherapy drug. The primary endpoint was to see whether adding immunotherapy to lenvatinib improved survival. And this was a negative trial. It did not show an improvement in survival for adding pembrolizumab to lenvatinib over lenvatinib alone, and there was really no significant difference in the time that patients were on treatment. The response was slightly higher with the addition of pembrolizumab to lenvatinib, but again there was no survival difference. So this combination will not move forward. And again, as I said earlier, the new standard first-line treatment is atezolizumab plus bevacizumab.

In colorectal cancer, probably one of the most exciting presentations was the use of immunotherapy treatments in locally advanced colon cancer. There is an important subset of colorectal cancer that has what's called an MSI-high status. MSI-high colon cancers are very responsive to immunotherapy drugs, and there has been a lot of interest in patients with localized colorectal cancer using immunotherapy drugs prior to surgery rather than conventional chemotherapy or radiation. So this important trial looked at 112 patients with localized colorectal cancer. Most of the patients were stage 3, and they all were documented to have this MSI-high status, which indicated a higher chance of response to immunotherapy. And patients received a brief course of immunotherapy, 2 doses of the drug nivolumab combined with 1 dose of ipilimumab over only 6 weeks followed by surgery. What they showed in these 112 patients who went to surgery, there was almost 100% response to this treatment. In fact, almost two-thirds of patients had no cancer found at surgery, even only after several weeks of immunotherapy. And in the 112 patients treated, there have been no recurrences in any of these patients.

So it's quite remarkable that immunotherapy could induce a complete remission in two-thirds of patients, and that was only after a few weeks of exposure of the drug. So I think we're going to see more interest in using immunotherapy treatments as a potential pre-surgical treatment for colon cancer. And we could argue with such a high rate of complete remission, if we gave immunotherapy longer, maybe we could consider nonsurgical management, to just keep treating the patients with immunotherapy. This is actually the case that's now been seen in rectal cancer, a recent study presented from my institution where they treated patients with rectal cancer with immunotherapy, and we also achieved 100% remission, and none of the patients in this small study required surgery. So I think this important study, which is called the NICHE-2 trial, indicates a high degree of effectiveness of immunotherapy in MSI-high colon cancers. And certainly, it raises interest in using this as a preoperative treatment and potentially could lead to some patients getting treatment with immunotherapy alone without surgery.

Then I'm going to comment a little bit about advanced metastatic colon cancer. Another important presentation was studying a new drug called fruquintinib. Fruquintinib is an oral drug that targets the VEGF pathway, which is an angiogenesis pathway in colon cancer. Standard treatment for colon cancer when it's stage 4 disease is now use of chemotherapy, like FOLFOX and FOLFIRI, drugs like bevacizumab, cetuximab, and panitumumab. And in more chemotherapy-resistant cancers, we use drugs like regorafenib and TAS-102. So this trial looked at a large group of patients, over 690 patients who had received all conventional treatments. They had progressive disease on all conventional treatments, including the late-line drugs regorafenib and TAS-102. And this was a placebo-controlled trial in which patients either received the drug fruquintinib or they received placebo plus supportive care. It was reasonable to offer a placebo in this trial because there really was no other standard treatment option for these patients. The primary endpoint of overall survival was improved with fruquintinib. Survival was improved with a reduction in the risk of death by about 30% and improvement in time on treatment. Very few patients responded to fruquintinib, so this was largely a drug that stabilized the cancer, but it did lead to modest improvements in time on treatment and modest improvements in survival. So this drug may potentially be evaluated as a new treatment option in very chemotherapy-resistant colorectal cancer.

I just want to mention briefly another new class of agents for which we had data presented at the ESMO meeting. These are drugs that inhibit a mutation in their cancer called KRAS G12C. There are promising drugs that target this pathway. And there were 2 drugs that were followed up on at ESMO, one was a drug called sotorasib and another drug was adagrasib. These are drugs that target KRAS G12C mutations in colon cancer. And both of the trials that were presented used these drugs combined with drugs that target the EGFR pathways, so either panitumumab or cetuximab, and very encouraging responses were seen on these trials. The trial that looked at the combination of adagrasib plus cetuximab achieved a response in about 46% of patients, which is very encouraging. The trial that studied sotorasib, combined sotorasib with panitumumab, and they observed a 30% response, and some of these responses were durable. So the take-home message is that these drugs, adagrasib and sotorasib, are promising new agents to target KRAS G12C mutations in patients with advanced colon cancer and indicate that we may get even a higher degree of activity when we add EGFR-targeted drugs including panitumumab or cetuximab to these agents.

So the other area that I want to comment on is gastric cancer. Recently, in the United States, we had a regulatory approval for the drug trastuzumab deruxtecan in patients who have HER2-positive gastric cancer that's advanced and is being treated with chemotherapy alone, HER-2-positive patients who had received previous trastuzumab or Herceptin. So trastuzumab deruxtecan is a promising drug used in patients that develop resistance to trastuzumab. So there was an update of the trial called Gastric-DESTINY02, which was a phase 2 trial of trastuzumab deruxtecan in Wwestern patients as a second-line treatment for patients with HER2-positive gastric cancer, and the updated analysis again showed a promising response in 40% of patients. The response duration was about 8 months, and patients achieved a survival of a year or more. So this updated presentation really reinforced that this is an active drug for patients with HER2-positive gastric cancer whose disease progresses on previous treatment with trastuzumab.

So this was a very exciting ESMO meeting. There were a lot of other studies and important presentations, but I've tried to highlight today what I think are the most important as we move forward in trying to identify new treatments for patients.

ASCO: Thank you, Dr. Ilson.

Next, Dr. Sumanta (Monty) Pal and Dr. Tian Zhang discuss new research in kidney, bladder, and prostate cancers.

Dr. Pal is the co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and is a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center.

You can view disclosures for Dr. Pal and Dr. Zhang at Cancer.Net.

Dr. Pal: Welcome to this Cancer.Net podcast. My name is Monty Pal. I'm a medical oncologist in the City of Hope in Los Angeles. I'm thrilled to be here today with my dear friend and colleague, Dr. Tian Zhang from UT Southwestern. Tian, mind giving us a quick intro?

Dr. Zhang: Hi, Monty. Great to be here with you today. Tian Zhang at UT Southwestern in Dallas, Texas, where I'm a GU medical oncologist. I'm really excited to talk through the ESMO trials with you today.

Dr. Pal: A little bit of housekeeping first. Let's go ahead and get some of our disclosures out of the way. I get travel support from CRISPR Therapeutics and from Ipsen. Tian, how about you?

Dr. Zhang: Sure. I've received honoraria from Exelixis, BMS, Genentech, AstraZeneca, and Janssen, all relevant to our discussion today.

Dr. Pal: Very good, very good. Well, thank you so much for joining us today. We've got a lot to talk about in about 15 minutes. The first thing that I wanted to chat about is adjuvant therapy. First of all, before we dive into the weeds here, can you just kind of tell our audience what adjuvant therapy is in broad strokes?

Dr. Zhang: In kidney cancer, we think a lot about how we might prevent disease recurrence after surgery. So adjuvant treatment refers to systemic treatment that's given after a big surgery. And so in kidney cancer, that's usually after nephrectomy or removal of the kidney.

Dr. Pal: Excellent, excellent. You beat me to the punchline. We are going to focus on kidney cancer, no doubt. This year at the European Society of Medical Oncology, or ESMO, meeting, which was held in early September, we actually had some really key studies presented in this space, one of which I'll disclose that I led. Studies I would say were maybe a little bit disheartening there, but nonetheless, I do think we can learn a lot from them. One of these trials was called PROSPER. This was a really interesting study that actually didn't just look at adjuvant therapy but actually looked at treatment before surgery, which we called neoadjuvant therapy. Tian, can you kind of walk us through the design of that trial really quickly?

Dr. Zhang: This was a trial done in the ECOG Cooperative Group, and patients were randomized to receiving either nivolumab, which is an immune checkpoint inhibitor, before surgery, followed by a year of nivolumab after surgery, or to surgery and observation with ongoing scans. So it was really trying to look at a perioperative approach of using nivolumab.

Dr. Pal: So how about this? Maybe we'll kind of discuss some of these results in amalgam, but maybe let's go through these trial designs first. The second trial that was highlighted this year at ESMO was called IMmotion010. That's one thing that I just love about these studies. They all have very clever names. I don't know what an IMmotion is, but tell us about IMmotion010 and what that trial design looked like.

Dr. Zhang: Sure. So IMmotion010, again, also was an adjuvant trial for resected intermediate- and high-risk kidney cancers, randomized folks to either atezolizumab for a year or placebo for a year. And so this is in the context of having had resected kidney cancers and following folks for the treatment results, and the primary endpoint there was disease-free survival.

Dr. Pal: Okay. So we've got an immune therapy called nivolumab and the PROSPER trial that was looked at before and after surgery. We've got atezolizumab, a different checkpoint inhibitor that was looked at following surgery. Tell us about the third trial. This is the last study in the space called CheckMate 914. What did that trial look at?

Dr. Zhang: That one, again, also a phase 3 adjuvant trial, enrolling folks after surgery that had high-risk kidney cancer and randomized to either the combination of nivolumab with ipilimumab, both checkpoint inhibitors versus placebo. And again, this treated patients for about 6 months and also primary endpoint of disease-free survival.

Dr. Pal: Now, whenever we do these studies, we always define them as being positive or negative, and that's really not meant to sort of cast any aspersions on how well the study was done or any really sentiments around the trial itself. It's really objective, and it's based on whether or not a study hits what we define ahead of the trial as being called a primary endpoint. So we actually, in these studies, looked at a primary endpoint of something called recurrence-free survival. And so that's really the proportion of patients who actually are living on without any sort of recurrence of their kidney cancer. I think it might be easy enough to sort of describe whether or not these trials hit that endpoint were positive or negative. What was the final report here on these trials, Tian?

Dr. Zhang: Well, Monty, I think all 3 of these trials were, quote-unquote, "negative," and we all had high hopes for all 3 of these trials. And certainly, many, many patients participated, and we will learn eventually a lot from these trials. But none of these 3 met their prespecified primary endpoint of recurrence-free survival endpoint.

Dr. Pal: So this is a little bit tricky because we did have these 3 negative studies presented at ESMO this year, but there was 1 positive trial that's adjuvant or postoperative space presented previously and then now published, actually, in the New England Journal of Medicine with an FDA approval to boot. Can you tell us about that, Tian?

Dr. Zhang: Well, that one was called KEYNOTE-564 and randomized patients to either a year of pembrolizumab or placebo. And so you're absolutely right. It did show an improvement in disease-free survival comparing pembrolizumab with placebo. And so pembrolizumab is approved in this adjuvant setting after nephrectomy.

Dr. Pal: And so this can be kind of a tough space because I can imagine our listeners are hearing this saying, "OK. Well, at ESMO, we've got 3 negative trials looking at postoperative therapy, and we've got 1 positive trial looking at pembrolizumab in the space." So what's one to do in this setting? What are you telling patients these days about whether or not to use adjuvant treatment for kidney cancer?

Dr. Zhang: Yeah. I think it's a conversation that patients have with their oncologist after surgery, and it really depends on their own risk factors, their clinical and pathologic features at the time of resection. It depends a lot on patient preferences and their own priorities and things such as their tolerance for toxicity or how often they're coming into the treatment center. And I do think this is a time point where they have a shared decision-making that we can help our patients understand the totality of the data and then decide if a year of pembrolizumab is worthwhile or if they'd rather continue with surveillance after surgery.

Dr. Pal: I totally agree with you, and I love that term "shared decision-making," because it's never one of those situations where I walk into the clinic room and say, "Here's what you're going to do." And it's also never the situation where the patient walks into the clinic room and says, "Here's what I want." It's always this really sort of mutual process, isn't it, where you sort of look at a patient's clinical state. You look at some of the features under the microscope, but then it comes down to really, really lengthy and personal discussions around what that patient wants to get out of treatment. So I think that's very well said, Tian. 

I'm going to move to actually a different setting, which is termed "metastatic disease." So we've talked about localized kidney cancer, where the disease is sort of confined to the kidney for the most part. We talked about what we do after we remove visible evidence of disease. But there is, unfortunately, a number of patients where we can't necessarily remove all the disease burden. So we lean more heavily on what we call systemic treatments. These are treatments that enter into the bloodstream either by mouth or through the veins. And in kidney cancer, just to give you a really, really brief synopsis, there's been this huge evolution over time. When I started in the field, it was really the advent of using a single oral therapy for kidney cancer. And over the next five 5 years, we sort of saw this evolution towards using doublet therapies, which is a mix of pills and IVs or maybe IVs alone. And more recently, there's been a lot of excitement. You can probably see where this is going, right? We've looked at 1 drug, and it works. We've looked at 2 drugs, and they seem to work. Logic would perhaps suggest that maybe you could get away with using 3 drugs in concert. So, Tian, this year at ESMO, there was a really important trial called COSMIC-313 that looked at 3 drugs versus 2 drugs. Can you tell us a little bit more about the design of the study?

Dr. Zhang: COSMIC-313, the large phase 3 study, which randomized more than 850 patients to either the triplet, as you're speaking of, the cabozantinib, nivolumab, and ipilimumab versus nivolumab and ipilimumab with placebo standing in for cabozantinib. And so this was a very large trial, looking particularly at progression-free survival, comparing the triplet versus the immunotherapy doublet.

Dr. Pal: And then tell us about the results of this because I have to tell you. I mean, I spent a lot of time looking over this, and I struggled with the end results a little bit. We talked about the primary endpoint of studies when we were discussing adjuvant therapy. And one of the things we'd mentioned is that you decide on this beforehand. And the primary endpoint in this trial was actually the delay in cancer growth. And as you pointed out, the study met that endpoint. But how do you interpret the results overall? How are you incorporating triplet therapy now?

Dr. Zhang: Sure. I think it did certainly meet the progression-free survival primary endpoint. The median was not reached for the triplet versus 11.3 months for the doublet. And so importantly, I think it was a, quote-unquote, "positive trial." But how are we using this? Well, we have not seen the overall survival data of these patients. And so when you're thinking about combining all 3 drugs in the frontline setting, I think it's really important to think about what might come after and whether these folks truly live longer with using all 3 upfront versus a sequential approach. So I think the jury is still out. It certainly met its primary endpoint, and it's quite promising. But I'm still waiting for the overall survival data to really inform or change my practice.

Dr. Pal: I've got to agree with you there. One of the things that we always discussed in clinic is whether or not a particular treatment strategy is going to increase longevity. It comes up in every conversation, I would say, whenever we're thinking about approaching a new line of treatment. And I wish I could say definitively that this triplet strategy improves longevity, but to be totally fair, that data just doesn't exist yet. So it's a really difficult conversation. I agree with you. Maybe a little pause before we start incorporating triplets.

So I've got to say, it was certainly a big year for kidney cancer, one of my fellows put this table together, and it really showed that this year amongst the past maybe 10 years in kidney cancer, we had more big phase 3 trials being reported as more than any year previously. But there are also some pretty key developments in other diseases that you and I treat, Tian, and one of those is bladder cancer. And a trial that I think was really quite important has the name EV-103. Tough name to remember, but it actually looked at a disease space that I think can be a bit of a challenge for us, and that's the patient who is presenting in the clinic has actually advanced bladder cancers spread to other parts of the body and is quite ill and perhaps can't receive conventional aggressive chemotherapy with a drug called cisplatin. So what did this proportion of EV-103 that was presented show us?

Dr. Zhang: Well, people hear about Cohort K thrown around, and so this trial actually has had multiple cohorts. And this particular cohort came out of some really exciting data from their dose escalation studies, and also Cohort A, where patients were treated with an antibody drug conjugate, this enfortumab vedotin, or EV, with an immune checkpoint inhibitor called pembrolizumab. And in the early cohort of 40 patients, they saw a pretty high objective response rate. That means the rate of patients where tumors were shrinking. And so that was about 70% of those 40 patients had objective responses. And so they designed this Cohort K to randomize patients to either enfortumab vedotin with pembrolizumab or enfortumab vedotin on its own, which has been approved in refractory metastatic urothelial cancer but particularly for first-line cisplatin-ineligible patient population. And so they randomized about 150 patients in the setting and looked at objective responses, and I agree with you. Certainly, very promising in terms of having objective response rate of about 65% and compared with enfortumab vedotin on its own, which came in around 45%. It does seem that this combination has more activity than the monotherapy.

Dr. Pal: Yeah. That's a great summary. And to the patients out there listening, when we talk about responses, we're talking about pretty deep responses here, meaning 30% or more reductions in the size of tumors. And Tian mentions that you've got 65% to 70% of patients with these responses. It really does entail a sizable reduction, not just a small decrease in the volume of tumors. And I'm telling you, just from having been in the scene for 15 years now, I mean, it's just remarkable sort of progress that we're making. 

We're going to wrap up by talking about prostate cancer, and just to really describe some overarching results. So there's a setting in prostate cancer that I always find to be a bit of a challenge, and these are patients who have had surgery for their prostate cancer. So extensively no visible spread of their disease, but they start having their PSA creep up afterwards. And there was a trial that sort of addressed that. Tian, can you give us the sort of quick and dirty summary of the study?

Dr. Zhang: Sure. So we call this PSA recurrence or biochemical recurrence setting. And this trial was led by Dr. Rahul Aggarwal in the Alliance Cooperative Group. But everyone who had biochemical recurrence were randomized to receiving androgen deprivation therapy alone, which is usually our standard of care; a combination of that androgen deprivation therapy with apalutamide, which is an androgen receptor blocker; or the combination of a triplet of the androgen deprivation therapy, the apalutamide, and then an abiraterone acetate, which is a blocker of steroid synthesis in the adrenal glands. And so this trial enrolled ultimately about 500 patients and randomized them 1 to 1 to 1 to these 3 cohorts. And interestingly, the combinations of either the androgen receptor, androgen deprivation therapy with apalutamide or the triplet with combined abiraterone acetate all prolonged PSA progression-free survival compared to androgen deprivation therapy alone. So I think it was a really well-done study in the cooperative groups and helps answer some questions around intensifying treatment in that biochemical recurrent space.

Dr. Pal: Yeah. These cooperative groups studies, each one of them are so critical. These are just funded by our federal government, and they really offer us a chance to really ask pure questions, so really, really important study design. And maybe in 30 seconds, let's go over this last study over here. I don't want to keep our listeners on for too long, but there was a study called PROpel. Again, you got to love these study names. So this PROpel study looked at advanced prostate cancer. So again, this is prostate cancer where the disease has spread from the prostate to other organ systems. This is potentially a new paradigm for the disease. Before, we used to just basically give everybody hormone therapy in this setting. We've doubled down and given patients more advanced hormonal therapy with drugs like abiraterone that you alluded to, but now there's this potential to use targeted treatments. And maybe you can tell us a little bit about how that's been incorporated in PROpel, Tian.

Dr. Zhang: Sure. Well, PROpel randomized patients to a combination of abiraterone with olaparib, which is what we call PARP inhibitor, and it blocks DNA damage repair, basically, in cancer cells. And olaparib has been approved as a single agent in more refractory, metastatic, castration-resistant prostate cancer. And so this trial randomized folks with a combination in sort of earlier lines of castration-resistant disease to either that combination or abiraterone with placebo. We saw earlier this year, actually, that the primary endpoint was improved for all comers, but I don't know if we saw some more subgroup analysis of patients with BRCA alterations and also with homologous recombination repair alterations. And I think that's very important, the fact that we saw more of an improvement in those subpopulations than those patients without the BRCA alterations or the homologous recombination repair mutations.

Dr. Pal: Excellent. Excellent summary. I think that's about all that we've got time for today. New paradigms in prostate cancer and bladder cancer potentially and a massive amount of new data in kidney cancer to things going forward with clinical practice from ESMO 2022. Tian, thanks so much for joining me today, and I hope everyone listening enjoyed this as well.

Dr. Zhang: Thanks, Monty. Take care.

ASCO: Thank you, Dr. Pal and Dr. Zhang.

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At the 2022 ASCO Annual Meeting, registered nurse, breast cancer survivor, and patient advocate Stephanie Walker presented the results of the BECOME Research Project, which looked at Black patient participation in metastatic breast cancer clinical trials.

In this podcast, Ms. Walker shares her story with Dr. Manali Patel, a medical oncologist and Assistant Professor of Medicine at Stanford University, as well as the Cancer.Net Associate Editor for Health Equity. They discuss Ms. Walker's experience with metastatic breast cancer, how she became involved with patient advocacy and research, and the work being done within the oncology community to make cancer clinical trials more equitable and inclusive.

View disclosures for Ms. Walker and Dr. Patel at Cancer.Net.

Dr. Manali Patel: Hello, I'm Manali Patel. I'm a thoracic lung cancer doctor at Stanford University and the VA in Palo Alto. And I'm a researcher that's focused on trying to improve and overcome health disparities and really trying to achieve health equity. I'm also the Cancer.Net Associate Editor for Health Equity. And today it's my great pleasure to talk with Ms. Stephanie Walker. Stephanie is a registered nurse, a survivor of metastatic breast cancer, and a leading patient advocate. She's the lead author of the BECOME Research Project on increasing Black patient participation in metastatic breast cancer clinical trials, which she presented beautifully at the 2022 ASCO Annual Meeting. Stephanie, we can't thank you enough for talking with us today. I'm going to first start off by saying that I am from North Carolina. And Stephanie, I read so much about you over the past few years and noticed that you are living in Tarboro, North Carolina. Is that correct?

Stephanie Walker: That is correct. I currently live there. We moved here originally in 2012, but this is my, I think, third or even fourth time living in North Carolina, moving back and forth between Thomasville and Durham and now permanently in Tarboro.

Dr. Manali Patel: Well, I love that we share our Tar Heel roots. I am a Tar Heel born, Tar Heel bred. When I die, I'm a Tar Heel dead. So I can't thank you enough for sharing those roots and then also for sharing your story with us today. You were first diagnosed with metastatic breast cancer in 2015. Can you tell us a little bit about your experience with that diagnosis and what it was like to be diagnosed?

Stephanie Walker: Well, actually the diagnosis in 2015 was my first diagnosis. I was not an early stager that had a recurrence, so I guess I could say breast cancer was never on my radar regarding family history. I thought maybe kidney disease or hypertension or those kind of things, but never breast cancer. So to say my life derailed at that time, it had. And I don't know if I ever grieved when I was told that I had metastatic breast cancer, I took it and just ran with it. I did not really fall off until many years later when I had to stop working. At the time I was diagnosed, I was working as an on-call nurse for a hospice company. So I was working 7 days on, 7 days off. So on my 7 days on is when I received a call and during my nap time. But yeah, it was very hard.

But like I said, I didn't think bad of it. When I did finally look it up and see that the life expectancy was like 36 months, that kind of kicks your butt into gear to do things. But I didn't do anything. I just continued to work. [laughter] I didn't stop working. So yeah, it went through the basic standard of care treatment of Adriamycin, Cytoxan, and Taxol. But I didn't get through my whole series of Taxol due to neuropathy and increased falls. So I stopped at 9 out of 12.

Dr. Manali Patel: Still 9 out of 12, it's difficult. And that's a difficult therapy and difficult regimen. You talked about how it derailed your life. And I know I've had the pleasure of reading your story online. I think what's also really interesting is that you had a role as a hospice nurse and over 40 years as a hospice nurse.

Stephanie Walker: No, most of my years of nursing was critical care. The last 14 years were hospice care, palliative life care. But, yeah, I just rolled with that. Even taking care of patients that had the same diagnosis kind of brought-- seeing death and dying every day. But then to see somebody with metastatic breast cancer dying was really hard.

Dr. Manali Patel: Yeah. And I'm sure that your experience at nursing on the other side and the flip side, and then when you became a patient, is quite different and maybe challenging in and of its own.

Stephanie Walker: A lot of people expected or said that. I think I got left out of a lot of things that could have helped my journey in the beginning, like a patient navigation and that kind of thing was kind of not given to me. And I guess it was because being a nurse. But I had no experience other than pediatric oncology. I knew what those children went through. And actually, it actually did help going through my treatment because I would remember this one little girl that was going through chemo, and she got up one morning and her pigtails started falling out, and then she wanted to get on the IV pole and go to the playroom. And I'm thinking to myself, if she can do it-- and I called her by name, if she can do it, what the hell am I complaining about? So it's like, just get up and go to the playroom. [laughter]

So I kept going back to that, you know what I mean? These kids that are innocent and have not even started to live their life going through this, and they never complained. So being an old lady at 56, being diagnosed, hell, who was I to complain about it? So just pick your hair up and keep going.

[laughter]

Dr. Manali Patel: That's right. Get your IV pole and go to the playroom.

Stephanie Walker: That's right.

Dr. Manali Patel: It's interesting that you mentioned that being from the nursing field and from the medical field kind of excluded you from a lot of what we hope other people receive, which is good education about their diagnosis. And like you mentioned, a patient navigator. Do you think that being a Black woman in any way, shape, or form shaped your experience with cancer, and if so, how?

Stephanie Walker: It didn't in the beginning. Like I said, from 2015 up until 2018 when I found myself suddenly without a job or insurance, I had no idea. I didn't know anybody else with metastatic breast cancer. I didn't know what was out there. I guess I didn't have a need that was not met. I had insurance that was paying the bills. I had a husband that helped care for me, 2 adult children that looked in on me, a job that I didn't consider a job, it was a calling, and I had no needs at that time that weren't met. So I didn't have the desire or the need to look outside my little tiny world, I guess, until I found myself in 2018. In 2017, we moved late in the year back to North Carolina from Louisiana and started a new job as a hospice nurse, same kind of a schedule and was out shopping with my husband one day, and I kept saying, "I'm really short of breath." And I said, "All this weight I've gained since treatment, it's horrible. I'm just fat and can't breathe." And he just kind of laughed at me and said, "No, you're fine, you're fine." Well, then I started experiencing chest pain and I said, "I think I need to go to the ER."

And for me to say I need to go to the ER, then my husband kicked it into gear and thinking, "Oh gosh, maybe so." Went to the ER, thought I was having an MI [myocardial infarction, a heart attack], ruled that out, and sat back in the lobby for a couple of hours and then they came and got me again and, in a hurry, said that they'd seen that I had a blood clot in my left lung. So it's like, great, here I am now with the PE [pumonary embolism] and having to be on blood thinners. And then I had a TIA [transient ischemic attack, sometimes called a ministroke] on an oral blood thinner. So obviously that failed me. So that's when I had to stop work. And then that's when I went into a deep depression. And people say it's like just because you have to stop work, you get depressed and it's like, yeah, I mean, I had always told myself in the very beginning of my diagnosis, I'm going to work up until the very end. And then not to have that-- and I felt like if I don't do anything, I'm going to die quicker. So I did not know what I didn't know until I found myself trying to figure out how I was going to live, pay bills, eat, pay for treatment.

You know, when you don't have that comfort, then I started looking for ways to help provide until I could figure out a plan. And that's when I found the world of metastatic breast cancer and advocacy that I went to my first metastatic breast cancer conference: Living Beyond Breast Cancer, actually in April of 2018. And I don't remember the weekend because I was just in awe that all these women around me had metastatic breast cancer and were thriving. And more than that is I've seen a whole lot of Black people that were like me. So I wanted to know more, learn more, do more. So that's when my whole-- I tell people that was my coming out party of metastatic breast cancer. So I did research trying to find funding and I spent 8 hours a day, 5 days a week looking for that since I didn't have a job, I didn't know what else to do. And luckily, I found enough resources to stop the bridge until I got my first disability check. Nobody told me there was a 5-month waiting period, right? And I found the insurance, thank you to my cancer center, provided ways for me to continue treatment because I made an appointment to tell them I'm going to stop treatment. I can't afford to pay you. But they came through, and I'm thankful for that. So that's when the world of advocacy opened up. It was in 2018, about 3 years after my diagnosis.

Dr. Manali Patel: I love that you think and were part of the calling and your identity of being a nurse, and then of course as a hospice nurse, especially, but losing that identity, but then channeling and refocusing and helping other people and really advocating has given me a lot of inspiration as a daughter of a mother that also faced similar challenges.

Stephanie Walker: I'm so sorry.

Dr. Manali Patel: I really want to thank you for all that you've done on behalf of all women with breast cancer, and especially for Black and Brown community members who have breast cancer. We've read your story and know about you and so are really just thankful for you and the research that you've been doing, especially the research that you presented this past summer at our ASCO Annual Meeting 2022, where you presented the results of the BECOME Research Project. I was hoping that you could give us some background on the study and why you wanted to do research in this particular area?

Stephanie Walker: First and foremost, I'm not a researcher. I don't like research, [laughter] and I didn't plan on doing research. So with that being out of the way, I am a nurse. I am a critical care nurse. I am a hospice nurse. I am an advocate. Researcher, not. So actually, it was done because there was another metastatic breast cancer huge advocate, Marina Kaplan, who is no longer with us. I met her at the San Antonio Breast Cancer Symposium in 2019, and she had done a poster presentation regarding patient-centered outcomes as well. And she noticed that the Black respondents to her survey was less than optimal. She only had like 8% return. And she said, "Stephanie, I don't understand, why so low?" And it was like, "Marina, I don't know. I did your survey, so I can't tell you." So she said, "There's got to be a reason." And she said, "Let's delve into trying to find out why." And she said, "How about this? You do the survey. You gear it to the Black population, men and women with metastatic breast cancer, and I'll help you."

And I said, "You're definitely going to have to help me. I'm not a researcher. I don't do statistics either. I found that I didn't need that when calculating medication doses." Anyway, so with that being said, she said, "I'll do it. I'll do that part for you." And I thought, me being simplistic, how hard can it be to do a survey, right? You have questions, you put them on a piece of paper, you print them off, you make 100 million copies, and you send them out to people or you ask people in one of your Facebook groups or something, and you just write down the answers. That is not how it's done in the research world. So, unfortunately, before we could get it off the ground, she passed away. And actually, she was very sick at the conference. So she passed away actually the following January-- February. So I kind of put it on the shelf in the back of my mind because I just assumed that was just between me and her. Nobody else knew. She had told somebody else, and they came back to me. It was actually someone at Living Beyond Breast Cancer, Janine.

She came back to me. She said, "Hey, do you remember when Marina talked to you about X, Y, Z?" And it's like, "Here it comes." And I said, "Yeah, sure." And I told her I would get it done. I told her I would do it. I told her I would do it. And people said, "She's gone. You don't have to do it." And it's like, "My word is my word." So she introduced me to a group at the Metastatic Breast Cancer Alliance, the information task force, and they looked at it and thought it was a great idea and picked it up as one of their projects. And there I was starting my research problem with being the project lead of people that I didn't know, with an idea that I didn't know how it was going to be done. So I am thankful for a bunch of people, man, I am telling you. So it got done. It was partnered with a marketing and strategic group, CB White, and they actually got it off the ground to which way it needed to go. I didn't realize it cost a lot of money either. [laughter]

It started off, we did literature search. We found some ASCO literature that would support our survey. Then we did interviews with the patients, the clinicians, researchers, payers, and they asked the questions -- we formulated questions because we had a subcommittee and someone else did the interviews. And after those were all done, that's how the survey was formed. And the survey went out-- it basically went out via social media. And the subcommittee, it was a bunch of patients and industry people and from the Alliance that pushed us out and was supportive of it and really believed in it. And my goal was to get 500 respondents.

I wanted 250 Black and 250 of everybody else. I didn't care who, but I say I didn't reach my mark, and it was a little disappointing. I only had like 420-some people that responded. But everybody said that was really good because I didn't offer them anything. I didn't offer you money. I didn't offer you a gift card. I didn't offer you a cup of coffee. But it was done, and I'm proud of the responses. It was all done -- this whole project was done during the pandemic. And you have to realize that a lot of people in the subcommittee that I had that actually worked really hard, I had never met. So this is a group of people that you only know a face like on Zoom or something. So the results were some of them were -- I kind of expected that. But the biggest shocker for me was -- the number one thing that we're focusing on is a general ask, right? No one asked us, as Black men and women with metastatic breast cancer, talked to us about clinical trials.

Dr. Manali Patel: I think that that finding, can you briefly tell us the numbers for the readers? I've read through and also saw the presentation kind of what you found in terms of that being the biggest and then some of the other outcomes that you looked at.

Stephanie Walker: Well, some of the other outcomes were like, other than the 4 that we're focusing on, is to better inform, you know what I mean? We need Black patients to know about and to get the information to make informed decisions about clinical trials. That's first. Then the second one was to inspire trust. We all know about all the stuff in the past and the distrust of the Black community with health care providers. So we need to build that, and it has to start in a community in which the person lives. And we also found that more Black than non-Black, when questioned, would try a clinical trial only if they were asked to, but they weren't. So to ensure access -- there were barriers, obviously, to people wanting to participate in a clinical trial. And some of those were the travel time, the difficulty in finding the trials, worrying about the financial burden.

And a lot were like, if I go to another facility, is my insurance going to cover it? So that's a big thing. And the final was to address the concerns, legitimate concerns. We need the health care provider to communicate in a clear language that we understand, and also understand the reasons that motivate us to participate in a clinical trial. So with those 4 things, we came up with some actions to do. But those were the 4 big ones that I found out that needed to be addressed. Because when doing this, I didn't do it just to be doing it. I wanted to do it to find out what the barriers were and then to come up with actionable steps. And as a physician or anybody, there's all those surveys people want you to do, and then they stop there. They don't go on. And I'm one of these people, like, don't waste my time. Let's do something that's actionable that we can act upon or help other people to act upon.

Dr. Manali Patel: I think those of us in the health equity space, right, are not surprised that a lot of what you found does really play in terms of what the health care provider and what the health system can do. The health system can do things to engender trust rather than putting the blame on the patient, saying that patients don't enroll in clinical trials. Well, maybe we aren't asking patients equitably if they're enrolling. And we need to take a hard look at our own selves and our own practices and think about what we can do similar to a checklist, right? When a patient comes in, how can we make this part of standard of care to make sure that everybody gets asked, and we've got all these fancy decision support tools and our electronic health record that turn up poppers of, "Did you ask the patient about this?" But making this part of the rubric of what we do, I think was really nicely highlighted in your study and your findings.

Stephanie Walker: Yeah. And I truly agree. Rubric metric, however you want to say it, people are like, "Well, how are you going to get them to change it?" Like, first of all, with education, and second of all, man, if I could figure out a way to attach a dollar sign to that rubric or that metric, it would be great. 

Dr. Manali Patel: I think for our readers, you and I know and really want to get the messaging out for equitable and accessible clinical trials. Can you explain from your perspective why it's so important to be inclusive and to have clinical trials that are accessible and equitable for all patients with cancer?

Stephanie Walker: Well, the statistics speak for themselves. Only like 6% of participants in a clinical trial for a metastatic breast cancer are, like 6%. But it's important that the clinical trials are inclusive for everybody, all people, because you want the medications to work for quote-unquote "all people." And we find that, speaking from just my experience and what I know and have heard, that there are treatments out there that don't actually work on Black people. And one of the big general ones is one of the blood pressure meds we have found recently that does not work or do not work very well with people of color. So we have to include everybody in these clinical trials to be able to have effective treatments to work for everybody, no matter where they are, where they live, who their doctor is, what hospital they go to. All people need to be included. And we find that 80% of the patients are treated in community cancer centers, and those are the patients that are usually left out just due to the fact they're not associated with a teaching medical institution/NCI facility.

Dr. Manali Patel: I think this is so important and really appreciate you highlighting that important fact is that making sure that our treatments are effective and feasibly can be provided to all patients in our quest for achieving health equity. What work is currently being done to make clinical trials more inclusive?

Stephanie Walker: Everybody is working on that. Even Stephanie is working on that. With a new subcommittee, a little branch out from BECOME, we found that -- we had just spoken of education. And so we came up with an idea of an actionable step. How do we do that, and how do we educate the health care providers regarding all of these facts that we found? And we are going to have a symposium. We came up with a symposium, a 1-day event. And we are going to attach it to the San Antonio Breast Cancer Symposium. We're actually going to have it the day before the symposium starts and hopefully, that will attract health care providers who we're targeting this to come and just listen to see what the patient has to say. We have it broken into 3 sections. The first section is about the health care provider, how to communicate with your patients.

What does it look like on the other side? And then the other is broken down into the pharmacy or pharma industry section. What are they doing to help include all people in clinical trials? And a lot of them have jumped on that bandwagon to be inclusive. But really, what are you working on? I want to know. So that's the second session. And the third session is about the patient and the caregiver. From the patient's point of view, how they did with clinical trials, and also a clinical navigator, what their role is to help patients find out about the trials and be that support person and as well the caregiver. A lot of people forget the caregiver goes through this as well. And to get the view of what the caregiver had, what they had, what they needed, what they didn't receive, to find out that so we can provide those things for them, hopefully. But yeah, that's what we're doing now. We're still in the planning phase.

Dr. Manali Patel: That's amazing. I love the action-orientedness of really moving to the next step, taking the findings that you found, moving towards really action, and bringing all of the partners together. I know that all the industry partners and really holding people accountable for what they are planning on doing. I love that. What actually are you doing and coming up with a plan for moving forward?

Stephanie Walker: Yeah, you have to start holding people accountable, get rid of the biases. And I've been blessed that I had not experienced any kind of biases in my care until the pandemic. And that was when I wanted to get my cancer treatment at a community center closer to home because it was a simple treatment of fulvestrant injection, and I wanted to get it closer to home. And we all agreed. We found a physician that would accept me closer to home. And it was going great until I started having complications, and he totally blew me off, actually. He told me that I needed psychiatric help, but he didn't know I was already getting it. But anyway, after contacting several patients that see this physician, they experienced the same thing. So that's the first time I had experienced anything based on my race and who I am. And that happens when a physician walks into a patient's room, sometimes that's what they see. They don't see Stephanie, they see a Black woman, and they start thinking in their head ticking off things like, "Oh, she's Black. She doesn't understand. She doesn't even know what a clinical trial is. She's going to be non-compliant. She's going to quit. And then she's going to become this angry Black woman that I'm going to have to deal with." So all of that before it is, "Hi, my name is." So, yeah. That experience made me want to do a little bit more to try to get rid of the biases that patients experience.

Dr. Manali Patel: Yeah, I think what you're doing to advocating, not only us clinicians, I'm so sorry that you have to experience that. Unfortunately, we've heard and know that it's sometimes the norm of what people experience or the systemic biases that then play into the role with implicit biases and then, unfortunately, lead to delays in care and also mistreatment or even lack of evidence-based treatment for people just based off of their skin color or from what community they may be from, or even how much income they may have or education level. I think what you said about what the work that you're doing and educating us clinicians, number one, first and foremost, what we can do with the health care system and looking at our own practices and our own policies and trying to reduce and remove some of the biases that are baked into the system. But then also what you're doing on the ground with other patients and advocating for patients. I want to close with 1 last question, and you've highlighted some of it, but if you were to give advice to people with cancer who are faced with needing to advocate for themselves, be it for care like you described, or for clinical trials, what advice would you give them?

Stephanie Walker: It's almost like having to put burden on the patient to learn. But you do. You have to become Ph.D.-certified with your own illness. You got to go out there and know what you got and know what you need, what the standard of care is, and that is the truth. When you get that diagnosis, I believe you should, first of all, take somebody with you with a notepad to be able to write down things. When you hear the word "cancer," you don't hear nothing after that. And you're only going to probably absorb a fourth of what you're told at the office. So have somebody to write down what the doctor says, suggestions, and research your plan of care. Find out what the standard of care is. I tell people, don't go to Dr. Google, but you're going to have to Google some things. But try to find vetted sites, reputable sites to do that. And there's lots of organizations out there that you can get the information from. And I don't want to say use Facebook, but believe it or not, there are great groups on Facebook that offer support, information, suggestions, "Hey, I'm getting ready to start this treatment. What happened to you? Or what do you think?" So always arm yourself with questions when you go in.

Ask the questions. Don't be afraid to ask. If that doesn't work, of course, with the pandemic, I would have people that want to go with me, and I couldn't go, but I could sit out in the lobby on my cell phone and listen in and encourage them to ask this question or ask the doctor a question. Of course, that has to be given with permission from the physician as well. But arm yourself with as much information as you can. And if you are finding that you're not getting that feeling of, "This doctor has my best interest," seek a second opinion, third opinion, a fourth opinion. Don't let a doctor railroad you into doing something that you don't understand. If you don't understand, speak up. I tell people all the time, they may know about cancer, but you know about yourself, so hold firm to that. I've told several doctors. I've fired several. So, I mean, they're out there. And I tell people all the time, don't be scared. Be comfortable and always know there's somebody out there. You're not alone to talk to. And being depressed or down sometimes, it's normal. You go there, but don't live there. If you find yourself living there, reach out for help. Because I'm one that thought that nurses don't reach out for help, but I finally did. So don't be afraid to ask for help and know that there's somebody out there with you. Call me. I'm available.

Dr. Manali Patel: Ms. Walker, I can't thank you enough for sharing your story with us and telling us more about your experiences and the work that you've been doing-- the important work you've been doing in this area. It was really wonderful to have you, and I hope that we get to meet in person at some point.

Stephanie Walker: I really thank you for the opportunity to share and hopefully the information that we both have provided, people will get it and understand it, and it will help somebody, because the work you done while you were at ASCO was amazing, too. So read that. [laughter] So I really do, and I really appreciate the opportunity.

Dr. Manali Patel: We are very grateful. And thank you for Cancer.Net, for hopefully being that source of trust and source of information for all of our patients.

ASCO: Thank you, Ms. Walker and Dr. Patel. You can find more stories from people with cancer at the Cancer.Net Blog, at www.cancer.net/blog.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in lung cancer, lymphoma, and childhood cancer that was presented at the 2022 ASCO Annual Meeting, held June 3-7 in Chicago, Illinois.

First, Dr. Charu Aggarwal will discuss 3 studies looking at treatment options for people with non-small cell lung cancer.

Dr. Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the Cancer.Net Associate Editor for Lung Cancer.

You can view Dr. Aggarwal's disclosures at Cancer.Net.

Dr. Aggarwal: Hello and welcome to this Cancer.Net podcast. I'm bringing you updates from the Annual Meeting of the American Society of Clinical Oncology, held in Chicago in 2022. I'm Dr. Charu Aggarwal. I'm the Leslye Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania's Abramson Cancer Center. I will be discussing updates on 3 studies today that offer insights and new advances in the management of patients with non-small cell lung cancer. I don't have any direct relationship with any of these companies or studies, and you can view a list of my disclosures on the Cancer.Net website.

First off, I would like to talk a little bit about advances in the management of patients with EGFR exon 20 mutations. We know that a lot of advances have been made in the management of patients with non-small cell lung cancer, and much of that has been attributed to the fact that we are now able to deliver targeted therapy for a subset of patients. EGFR mutations form one such subset where we have a lot of oral drugs that are available, and we can offer these that improve survival, and patients can avoid chemotherapy, immunotherapy, and other IV infusional therapies. Within the subset of EGFR mutations lies this unique subset of EGFR exon 20 insertion mutations, which have been historically harder to target with currently available EGFR inhibitors. And over the last 5 years, we have seen tremendous growth of opportunities, targets, and new drugs for this subset of patients. The mutations in this subset forms about 2% to 5% of all non-small cell lung cancers. But now we have 2 FDA-approved drugs in this space, one being intravenously administered, amivantamab, and another that is orally available, mobocertinib. We covered this in a podcast as well as a blog, so please check those out on our Cancer.Net website.

But building upon that progress, there is now another drug that was reported at ASCO. This drug is called CLN-081. And we saw preliminary activity in a phase 1 and 2 study of this molecule or this drug in patients with EGFR exon 20 insertion mutations. It's an orally available drug. The top line data is that it is safe, it is effective, it was tested in different doses. It was tested at less than 65 milligrams, 100 milligrams, and 150 milligrams, again, as I mentioned, administered orally, and we saw responses and patients that had previously received other therapies and may have progressed on other therapies. And what we found was that this drug also tends to have activity against brain metastases, which I think is this huge unmet need in the management of such patients. So I think more to come, but again, I think offers us an insight into what may be in the future, an attractive drug for our patients with EGFR exon 20 insertion mutations. So stay tuned, more on that in the future.

Shifting gears, I would like to now talk about one of the common mutations. So we talked about EGFR exon 20, which is about only 2% to 5%, but the largest subset of mutations in non-small cell lung cancer really revolves around KRAS mutations, and these form about 30% to 35% of all mutations in non-squamous, non-small cell lung cancer. And amongst this group there is another subset which is KRAS G12C non-small cell lung cancer, that forms about 13% of all lung cancers. We have 1 approved drug already in this space by the name of sotorasib that is FDA approved for the management of patients with this particular mutation after having received 1 prior therapy, be it chemo-immunotherapy or immunotherapy. At this year's ASCO meeting, we heard data from a study called KRYSTAL-1, which looked at the activity and safety of another molecule called adagrasib, which is an orally available drug targeting KRAS G12C, again, in a similar population of patients with advanced and metastatic non-small cell lung cancer harboring a mutation.

We found that this drug is again effective, the overall response rate was about 43%, the majority of the patients had stabilization of disease, about 80%, and many patients were able to remain on treatment with stabilization of disease. We found that this drug does have side effects and adverse events and most commonly of this were diarrhea, nausea, vomiting, and fatigue. Many patients did require dose reductions, but the activity of the drug remained despite dose reductions. Now, what would be the advantage of this drug against the currently available sotorasib? In another smaller study reported at ASCO, there seemed to be activity in the brain, including intracranial penetration with the use of this molecule, adagrasib, which has not been demonstrated before with other KRAS G12C inhibitors, so I think that makes it a potentially attractive option. Again, I will say that the report of this intracranial activity was in a very small subgroup of patients, so I think needs to be further corroborated in a larger study.

Shifting gears again and talking about our last study, so I would like to highlight what do we do if, in case, patients don't have a targetable mutation. I want to highlight that we do have a lot of available options, and we are continuing to improve upon available options. The way we treat such patients is by using immunotherapy, either alone or in combination with chemotherapy. But what do we do after this treatment stops working? Researchers from the Southwestern Oncology Group, or SWOG, launched a massive national effort called Lung-MAP, which is basically a clinical trial that evaluates several different strategies all at once, either for patients with targetable mutations or for patients without a targetable alteration. And they reported results from a study that evaluated the combination of pembrolizumab with ramucirumab in patients that may have progressed after frontline immunotherapy. Now, pembrolizumab is immunotherapy, so the concept was, can we continue immunotherapy beyond progression and perhaps get some synergistic activity by using ramucirumab, which is a drug that prevents blood vessels from forming in the tumor itself. It's an anti-angiogenic agent, meaning that it is a targeted molecule that prevents blood vessel formation and promotes tumor death. What they found was that patients that received pembrolizumab and ramucirumab were more likely to live longer, so overall survival was longer for patients with this combination compared to a physician investigator discretion choice, such as chemotherapy in combination with ramucirumab or other chemotherapies that are otherwise used in the second line setting.

And interestingly, we did not find a significant improvement in shrinkage with this combination of pembrolizumab and ramucirumab or a significant reduction in the time of progression-- or, sorry, prolongation of the time of progression of disease. But the overall survival findings are interesting, and I think that's why we are including them in this podcast because that's one of the approaches that is leading to an improvement in survival and improvement in outcomes. I will point out that this is a phase 2 study. These results would need to be validated in a large prospective phase 3 trial so that we can account for certain confounding factors that may have led to these results. Having said that, I think there's a tremendous excitement, there's tremendous excitement in this field. I gave you examples of, or highlighted, 3 studies: one in patients with EGFR exon 20 insertion mutations, another in KRAS G12C mutations, and the third in patients who may have already received either immunotherapy or chemoimmunotherapy. We will continue to update our Cancer.Net website with updates as they come through, new advances, new studies, so thanks for following, thanks for listening, and more to come. Stay tuned. Thank you.

ASCO: Thank you, Dr. Aggarwal.

Next, Dr. Christopher Flowers will discuss new research in treating people with different subtypes of lymphoma, including mantle cell lymphoma and diffuse large B-cell lymphoma.

Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and was appointed Division Head ad interim of Cancer Medicine in August 2020. He is also the 2022 Cancer.Net Associate Editor for Lymphoma.  

You can view Dr. Flowers' disclosures at Cancer.Net.

Dr. Flowers: Hello and welcome to this podcast that is a review of late breaking abstracts from the ASCO Meeting and recent updates in lymphoma. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and Interim Division Head for Cancer Medicine at The University of Texas MD Anderson. And it's my great pleasure to discuss with you some of these late breaking abstracts. I do have some disclosures that are related to the content that I will present from this year's ASCO Meeting and recent studies in lymphomas. Those are available at Cancer.Net. Those relate to my role as a consultant for the development of clinical trials in lymphomas and research funding that MD Anderson has received from companies related to my role in clinical trials in lymphoma and clinical trials across cancers.

So, the ASCO Meeting had a host of new information that was presented. Some of that information centers around key clinical trials. One that was a pivotal clinical trial, the SHINE clinical trial, looked at patients with mantle cell lymphoma, a rarer lymphoma subtype, that looked at the combination of bendamustine and rituximab, a standard chemoimmunotherapy combination, compared to that same chemoimmunotherapy combination, bendamustine, rituximab, plus the Bruton's tyrosine kinase inhibitor ibrutinib. Ibrutinib, as some of you may know, is a kind of therapy that is typically used in the relapse setting for patients with mantle cell lymphoma when they have their disease come back. And the SHINE clinical trial was looking at adding it to frontline therapy. What this randomized, controlled trial in the phase 3 setting found was that patients who received the combination of bendamustine, rituximab, plus ibrutinib had improvement in their progression-free survival, meaning that the time that it took for their disease to come back or them to have deaths related to the lymphoma was longer for patients who received this combination. About 2.3 years longer than the group that received bendamustine, rituximab, plus placebo. And in total, that led to a median progression-free survival of 6.7 years.

That study has now been published in the New England Journal of Medicine and was led by my colleague Dr. Michael Wong from MD Anderson. Dr. Wong also led another study that was presented at the ASCO Meeting looking at CAR T-cell therapy for patients with mantle cell lymphoma. That study has now been published in the Journal of Clinical Oncology, and it looks at brexucabtagene autoleucel, a kind of CAR T-cell therapy, where that-- the CAR T-cell therapy was successfully manufactured for 71 of the 74 patients in the trial. 68 of those patients received an infusion and the median progression-free survival, so the average amount of time that it took for patients to have progression of their disease, was about 25 months. And so a marked benefit for those patients who were receiving CAR T-cell therapy when their mantle cell lymphoma came back.

There also were major breaking abstracts at the ASCO Meeting in the area of diffuse large B-cell lymphoma. As many of you may know, diffuse large B-cell lymphoma is the most common type of lymphoma that occurs in the United States. And there was a breaking trial that was presented in December at the American Society of Hematology Meeting describing polatuzumab, a CD79b antibody drug conjugate, as a new drug in the substitution of frontline therapy for patients with diffuse large B-cell lymphoma in combinations with rituximab, cyclophosphamide, adriamycin, and prednisone, or the pola-R-CHP arm, that compared favorably to rituximab and CHOP chemotherapy, which has been the standard of care for patients with diffuse large B-cell lymphoma. And that trial showed an improvement in progression-free survival.

At this year's ASCO Meeting, Franck Morschhauser presented results from looking at subsets of that patient population. Those patients who had BCL2 by immunohistochemistry that was positive or MYC expression by immunohistochemistry that was positive, or both of those, what we call double-expressor lymphomas, those who have poorer risk than standard groups. And those double-expressor lymphomas, treated with pola-R-CHP, had improvement in progression-free survival compared to R-CHOP with a hazard ratio of 0.64 in that group. We also saw in a multitude of analysis that that supported the benefit of pola-R-CHP in patients with both BCL2-positive and MYC-positive diffuse large B-cell lymphoma.

Another area that has been very hot in diffuse large B-cell lymphoma clinical trials is the role of bispecific antibodies. Bispecific antibodies are antibodies that bind both to CD20, a marker on the diffuse large B-cell or the lymphoma cells, and to the marker CD3, which is a marker on T-cells which brings the normal T-cells of the immune system in close proximity to the lymphoma cells and then leads to immune-directed killing of lymphoma cells. The agent glofitamab is an agent that was presented by Michael Dickinson at this year's ASCO Meeting in an abstract. And in this study, 107 patients who received more than 1 dose of steady treatment went on to have complete responses in about 35% of patients. And this showed that glofitamab induced durable complete responses and had a very favorable safety profile in patients with relapsed and refractory diffuse large B-cell lymphoma. And in this trial, they compared that also for patients who had prior exposure to CAR T-cells and showed that responses were also good in those patients.

Another set of studies has also looked at bispecific antibodies and a whole host of other areas with multitude of other agents. Another study that was presented at this year's ASCO Meeting explored the use of bispecific antibodies in the frontline setting in combination with the R-CHOP regimen that I just discussed. In that study, Lorenzo Falchi presented results of the subcutaneous bispecific antibody epcoritamab in combination with R-CHOP. This was a relatively small study of 33 patients that showed that the combination of epcoritamab plus R-CHOP was something that was safe and tolerable. There were no new treatment emergent adverse events that led to discontinuation of epcoritamab in the study. And there are some adverse events that are of special interest that we see with the bispecific antibodies, and those include the kind of immune-mediated adverse events that we can also see with CAR T-cells, like cytokine release syndrome, or CRS, or neurologic toxicities that we can see there that are also called ICANS. What we've seen in this trial, that about 42% of patients had some form of cytokine release syndrome, but that most severe form of cytokine release syndrome, those that were greater than grade 3 in severity, was only in 3% of patients. And likewise, the neurologic toxicities, or ICANS, that were grade 2 was in only 3% of patients. Relatively few patients completed all therapy by the time that this was presented. Only 10 patients had completed 6 cycles of therapy, but that showed an overall response rate that was quite high in that patient population.

There were a whole host of other trials that were presented at this year's ASCO Meeting, and those portend improved kinds of outcomes on the horizon for patients with lymphomas across the spectrum. And I think it's an exciting time moving forward for clinical trials in lymphoma and hopefully, to see new therapies that emerge for the management of this disease.

One of those new therapies that happened outside of the ASCO Meeting was the recent FDA approval of CAR T-cell therapy in the relapse setting for follicular lymphoma. And this was based on the ELARA clinical trial. And I think the future is quite bright for therapies and for patients with lymphomas broadly.

ASCO: Thank you, Dr. Flowers.

Finally, Dr. Daniel Mulrooney will discuss new research in childhood cancers, including a study comparing treatment options for Ewing sarcoma, and several studies on neuroblastoma.

Dr. Mulrooney is an Associate Member in the Division of Cancer Survivorship at St. Jude Children's Research Hospital. He is also the Cancer.Net Associate Editor for Pediatric Cancers.

You can view Dr. Mulrooney's disclosures at Cancer.Net.

Dr. Mulrooney: My name is Dr. Dan Mulrooney from St. Jude Children's Research Hospital. I'm the Deputy Director of the After Completion of Therapy Clinic at St. Jude and primary care for survivors of pediatric solid tumors. The annual ASCO Meeting is typically quite busy and full of research presentations sharing knowledge and advances in cancer treatment and care.

Today, I'd like to highlight some of the exciting presentations in pediatric cancer. Please note, I do not have any relationships to disclose related to any of these studies. At this year's meeting, one of the highlights was a European study in patients with relapsed or refractory Ewing sarcoma. Ewing sarcoma is a rare bone cancer that typically occurs in adolescents or young adults. While challenging to treat, it is difficult to cure in patients who have relapsed, and studies are needed to improve the care of these patients. Investigators from 13 European countries and Australia and New Zealand studied the most common relapsed therapies, which include irinotecan and temozolomide, gemcitabine and docetaxel, topotecan and cyclophosphamide, or high-dose ifosfamide.

The study enrolled 451 patients between 2014 and 2021 and randomly assigned them to one of these four treatments. Based on response rates, the first 2 arms were dropped and the study was largely a comparison between topotecan cyclophosphamide and high-dose ifosfamide. The main outcome was event-free survival. Event-free survival is a common way in a clinical trial to see how well a treatment works. It measures the time from treatment that the patient remains free of complications, such as return or progression of the cancer. But investigators also looked at overall survival, toxicity, and quality of life. The 6-month event-free survival was better for high-dose ifosfamide at 47% compared to 37% for topotecan cyclophosphamide.

The median overall survival was also better for high-dose ifosfamide compared to topotecan cyclophosphamide. The results were best for children younger than 14 years old versus those 14 or greater. Toxicities included fever and neutropenia, nausea, vomiting, and diarrhea. Patients receiving high-dose ifosfamide had more neurologic and kidney toxicities, which might be expected since ifosfamide is known to affect these organ systems, while only descriptive measurements of quality of life appeared higher for those children treated with high-dose ifosfamide compared to topotecan and cyclophosphamide.

The strength of this trial is its large size, particularly for a rare cancer, and the fact that it randomized patients to the most commonly used treatment regimens for relapsed Ewing sarcoma. Importantly, data did not previously exist comparing these different treatments. While the results of this study are promising, clearly more needs to be done, and there was a lot of discussion at the ASCO Meeting about how to further improve survival in these patients. This study provides some information for doctors and patients, but importantly, provides data to advance future trials, which will concentrate on incorporating new targeted drugs with high-dose ifosfamide. This study is ongoing and is adding additional arms to continue to improve the outcomes for patients with relapsed or refractory Ewing sarcoma.

In addition to this study in Ewing sarcoma, several studies investigating neuroblastoma were presented. Neuroblastoma is the most common extracranial solid tumor in children and for children with high-risk disease requires intensive and prolonged treatment, including chemotherapy, surgery, radiation therapy, and stem cell transplantation. Treatment for these patients has improved since the introduction of immunotherapy, particularly an antibody directed at a particular antigen named GD2 on the neuroblastoma cells. One study showed improvement in outcomes using this antibody for children with relapsed or refractory neuroblastoma, and another study demonstrated feasibility of using this antibody earlier in treatment, which was not previously known to be safe and tolerable.

In what is called the BEACON study, investigators tested whether the antibody, called dinutuximab, would be effective when combined with chemotherapy for relapsed or refractory neuroblastoma. They enrolled 65 patients from 2019 to 2021 and randomized these patients to either chemotherapy alone or chemotherapy plus dinutuximab. The median age of these children was 4 years. The overall response rate, which means either a complete or partial response, was 18% for the chemotherapy-only arm but improved to nearly 35% for those treated with chemotherapy and dinutuximab. The progression-free survival was 27% for chemotherapy only and improved to 57% for those treated with chemotherapy and the antibody. There was no change in overall survival, though investigators think this may have been due to some patients who had progressive disease and crossed over to the antibody arm of the study.

This presentation was followed by a study from the Children's Oncology Group, which investigated the feasibility of adding antibody treatment earlier in the treatment regimen for neuroblastoma. Prior studies had used antibody later in treatment when the tumor burden is thought to be lower. The endpoint of this study was tolerability measured by toxic deaths or unacceptable toxicities, such as adverse reactions to the medication. For example, sustained low blood pressure requiring a ventilator or breathing machine, or severe neuropathy. 42 high-risk neuroblastoma patients were enrolled from 8 different children's hospitals between 2019 and 2021. 41 of the 42 were able to complete the induction chemotherapy plus the antibody. There were no toxic deaths or unacceptable toxicities. Importantly, 85% were able to complete the next phase of treatment, called the consolidation phase, and 79% were able to complete the following phase after consolidation, called post-consolidation. One-year event-free survival was 83%, and 1-year overall survival was 95%. Now, it's important to know these are still early results, and the trial recently closed, and some of the patients have only completed therapy within the last year. Both of these studies add to the knowledge of chemoimmunotherapy for children with high-risk neuroblastoma. These studies provide a foundation for larger randomized trials that will further advance the care of these children.

And finally, another study looked at race, ethnic, and socioeconomic disparities among children treated for high-risk neuroblastoma on Children's Oncology Group studies. There were no differences in event-free survival, but there were differences in overall survival based on ethnicity. The 5-year survival was lowest for Hispanic patients at 47%, 50% for non-Hispanic other ethnicities, which included Asian, Native American, Native Hawaiian, or Pacific Islanders, and 62% for non-Hispanic Black and non-Hispanic White children. Importantly, these investigators also studied household and neighborhood poverty. Overall, survival was lower for children living in poverty, though some of these differences went away when accounting for other factors, such as stage of disease or high-risk features. This study is important because it highlights the increasing need to collect data on clinical trials that may contribute to inequities in outcomes. While most studies collect data on the race and ethnicity of participants, other factors known as social determinants of health, such as income, neighborhood, education, access to health care, and insurance coverage, may also contribute to outcomes in pediatric cancer patients.

Overall, the studies highlighted here and presented at this year's ASCO Annual Meeting focused on difficult-to-treat cancers, such as relapse or refractory disease, and they have laid the groundwork for future investigations to continue to improve survival rates for all children diagnosed with a malignancy through improved therapies and by addressing potential social barriers. Thank you for listening to this brief summary of the new research in pediatric oncology presented at the 2022 ASCO Annual Meeting.

ASCO: Thank you, Dr. Mulrooney.

You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Maryam Lustberg discusses highlights from the Multinational Association of Supportive Care in Cancer's 2022 Annual Meeting, held June 23-25 in Toronto.

Dr. Lustberg is the Director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center; Chief of Breast Medical Oncology at Yale Cancer Center; Associate Professor of Medicine at Yale School of Medicine; and the 2022 President of the Multinational Association of Supportive Care in Cancer. She is also a member of the Cancer.Net Editorial Board.

View Dr. Lustberg's disclosures at Cancer.Net.

Dr. Lustberg: Hello, everyone. I'm Dr. Maryam Lustberg. I am chief of breast oncology at Yale Cancer Center, co-chair of Symptom Intervention Committee for Alliance Clinical Trials, and the new president of the international society of Multinational Association of Cancer Supportive Care, or MASCC. And I'm here to talk to you about updates from the meeting that happened in Toronto in June of 2022. I have no relationships to disclose relevant to the topics that I will be talking about today.

And there were 3 broad themes in the meeting that I would like to highlight for you. One theme was a global focus on disparities in the delivery of cancer supportive care. So we do know that even in North America, patients with different socioeconomic backgrounds, different races, different cultural backgrounds, may not have as full access to cancer supportive care services, and that can include access to symptom management, survivorship care, palliative care. The umbrella of cancer supportive care is quite broad, and it's really focused on supporting patients and their families throughout the care continuum in a very multidisciplinary, holistic way. And so what we're finding, unfortunately, similar to cancer treatment, access to the best supportive care in cancer can also face certain disparities in the U.S. and North America. And this is something that we talked quite a bit about in the meeting in terms of recognizing this as well as finding solutions for it. And similarly, globally, we know that access to symptom management strategies, access to palliative care, access to oncology rehab, all of these can be quite restricted in different regions of the world. So the meeting in Toronto was really a call to action to recognize this as a pressing issue for our global community. And we will be forming several task forces to really look towards solutions. And so we look forward in terms of looking at low-hanging fruit interventions that we can both provide in North America as well as globally so that really patients and families could have access to such an important part of cancer care.

The second theme of the meeting focused on digital technologies as well as the impact of COVID-19 on the delivery of cancer supportive care. We know that the pandemic certainly shook the world, and it also impacted patients' access to supportive care services. These were often the services that were put on hold, understandably, during the resource-lean times and restricted access to services during the pandemic. So this was something that we absolutely recognize that this happened. It impacted many patients and families, but we also, as a community, really came together to come up with innovative solutions. And one of these innovative solutions, what people have called maybe the silver lining in what happened during COVID, is that there was an increase in telehealth services, including telehealth care delivery of some of these supportive care services. So a lot of the meeting focused on how this was implemented, what access may have looked like. There's certainly disparities even here in terms of access to telehealth services. And also patient preferences and caregiver preferences also plays a great role here, where some patients really find telehealth to be a really comfortable solution for them. They don't have to leave their home, find parking, but others may find it less personal. So really, if we're thinking about personalizing cancer supportive care, I think there was a lot of discussion about making sure that we kind of understand which clinical situations may benefit from telehealth care delivery, which situations may do better with face-to-face, and ultimately to really involve patients and families in that decision and to make sure that we're engaging and not dictating policies without their full engagement. So this is something that we absolutely care deeply about.

The third theme focused on burnout. There was a lot of focus on clinician burnout, which we know was also something that was a tremendous issue during the pandemic due to workforce shortage across all health care disciplines. People have talked quite a bit about the great resignation, where many health care workers as well as people in other sectors actually resigned or could not work in the conditions that the pandemic necessitated. So there was a lot of focus on recognizing burnout in clinicians because that directly impacts how well we can take care of patients. So recognizing it and thinking about proactive solutions, including there was a wonderful speaker, Dr. Benjamin Corn, who has done quite a bit of research on hopefulness and really feeling hope, whether you're a caregiver, whether you're a clinician or a patient, was found to be a key measure or predictor of burnout. And this is not meant to minimize system issues or anything like that. But I think there was a lot of focus on self-management and self-efficacy, kind of recognizing burnout and trying to foster things that we can do ourselves to keep ourselves healthy mentally, emotionally, and spiritually so that we can continue to function in the health care setting and take the best care of our patients, which is ultimately our goal as an entire scientific oncologic community is to be more present, to be more engaged, to deliver the best evidence care whether it be in the realm of cancer treatments or cancer supportive care, I do feel it's all part of that full package. Thank you so much for listening to this podcast.

ASCO: Thank you, Dr. Lustberg. You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in head and neck cancer, brain tumors, and health equity that was presented at the 2022 ASCO Annual Meeting, held June 3-7 in Chicago, Illinois.

First, Dr. Cristina Rodriguez will discuss 2 studies on new treatment options for locally advanced head and neck cancer.

Dr. Rodriguez is a medical oncologist at Seattle Cancer Care Alliance, an Associate Professor in the Division of Medical Oncology at the University of Washington, and an Associate Member for solid tumor clinical research at the Fred Hutchinson Cancer Research Center. She is also the Cancer.Net Associate Editor for Head and Neck Cancers.

You can view Dr. Rodriguez's disclosures at Cancer.Net.

Dr. Rodriguez: Hello. My name is Christina Rodriguez. I'm a medical oncologist with a clinical and research focus on head and neck cancer. And today I'm going to discuss research on head and neck cancer that was presented at the most recent 2022 ASCO Annual Meeting. I don't have any relationship to disclose that pertains to the research that I will talk about today. I'd like to discuss 2 abstracts that I thought were practice changing or practice affirming that really addresses some of the key questions that patients and doctors like me have about the treatment of patients with head and neck cancer. So, as you know, most patients with head and neck cancer present with typically locally advanced disease, and most head and neck cancer patients are treated with the intent of curing them most of the time with the use of radiation either as the main treatment or after surgery. And many clinical trials have shown that when we add a chemotherapy called cisplatin to radiation, we improve curative outcomes for patients.

But the first abstract that I will talk about, abstract 6003, asks the question "What do we do for patients who are not candidates for cisplatin chemotherapy?" And we know that a significant proportion of our patients will have other medical problems that could make it difficult for us to give chemotherapy and often will result in complications or more toxicity or in side effects for patients. This clinical trial was carried out in India, and it compared radiation alone for patients with head and neck cancer versus radiation given with a non-cisplatin chemotherapy called docetaxel. What's unique about this clinical trial is that it's specifically focused on patients who were not candidates for cisplatin chemotherapy, something that really hasn't been done for this population. Interestingly enough, they found that when we give docetaxel with radiation in these patients, we find that they do better, they live longer, and they feel better based on quality-of-life questionnaires.

So I will say that this study, abstract 6003, tells us that even in patients who are not candidates for cisplatin to be given with radiation, there is an alternative treatment that we can use, such as docetaxel given with radiation, that might still improve patient's cure rates for their head and neck cancer.

The second study that I think was another interesting study was a clinical trial that asked the question, "Can we give cisplatin in an alternative manner for patients who are undergoing definitive radiation treatment as their main treatment for head and neck cancer?" Like I mentioned, the clinical trials that led to the use of chemoradiation as a standard use cisplatin given in larger doses every 3 weeks, but there's been concern about how well that approach is tolerated by patients. So this particular clinical trial compared patients receiving radiation as curative intense therapy for head and neck cancer with either the cisplatin given every  3 weeks or the cisplatin given at a lower dose once a week.

It's important to know that this trial was done in India, where the population is pretty different from what we see in the United States. These are mostly patients who have HPV-negative cancers, mostly cancers acquired through exposures like tobacco and alcohol. And what they found was that these 2 groups of patients had very similar outcomes. In other words, there didn't seem to be a reduction in the rates of cure when we give chemotherapy every week versus every 3 weeks. And interestingly enough, it looked like from a toxicity or side effect standpoint, the every week seems to be a little bit better tolerated. Patients who got the treatment every 3 weeks also had less need for hospitalization or IV fluids and less utilization of health care resources.

I think this is a very interesting finding because it really provides us with what we call high-level data that the weekly administration can work. I think it's important to recognize that the population that it studied for this particular clinical trial really was more an HPV-negative population. That's important to know because the standards for HPV-positive head and neck cancer are generated from larger trials that use cisplatin every 3 weeks. But we are continuing to study this question, and there's actually a large NRG study, HN009, that is asking that question both for the HPV- positive and HPV- negative population. So we are, I think, making strides in terms of asking the questions that allow our patients not only to receive treatment that is highly efficacious but also that limits side effects and toxicity. I will also mention that these trials were completed during the COVID-19 pandemic, which tells you that the dedication of these researchers to complete something like this in such a challenging time is to be commended. That's all I have to say, and thank you for listening to this brief summary of new research in head and neck cancer from the ASCO 2022 Annual Meeting.

ASCO: Thank you, Dr. Rodriguez.

Next, Dr. Glenn Lesser will discuss 3 studies that looked at new treatments for different types of brain tumors.

Dr. Lesser is the inaugural Louise McMichael Miracle Professor and Associate Chief in the section on Hematology and Oncology in the Department of Internal Medicine at Wake Forest Health. He is also the Cancer.Net Associate Editor for Central Nervous System Tumors.

You can view Dr. Lesser's disclosures at Cancer.Net.

Dr. Lesser: Hello. My name is Glenn Lesser, and I'm a professor of medical oncology and the director of medical neuro-oncology at the Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina. I'm also the editor of the brain tumor section for ASCO's Cancer.Net. And today, I would like to briefly discuss several clinically relevant research studies involving patients with brain tumors that were presented at this year's ASCO Scientific Program. Of note, I have no disclosures or relationships relevant to the abstracts I'll be discussing today.

The first presentation to talk about is a late-breaking abstract presented by Dr. Eric Bouffet, who described the results of a phase II trial of 2 targeted anticancer agents, dabrafenib and trametinib, in pediatric patients with a kind of brain tumor called a low-grade glioma, which harbored something called a BRAF V600E mutation in their tumor DNA. By way of background, gliomas account for about 45% of all pediatric brain tumors, and the majority of these gliomas are low-grade, which include World Health Organization grade 1 and 2 tumors. Common types of pediatric low-grade gliomas include pilocytic astrocytomas, gangliogliomas, and low-grade gliomas that are not otherwise specified. Now, mutations in the BRAF gene are common in certain kinds of cancers, particularly melanoma, and novel oral targeted therapies have been developed to effectively treat these tumors by targeting this mutant BRAF gene. A particular mutation in this gene called a V600E mutation occurs in about 15% to 20% of pediatric low-grade gliomas. The presence of this mutation is thought to lead to an increased risk of progression to a higher grade or a more malignant glioma in these patients, and these mutations in their tumors also predict a less favorable response to chemotherapy.

In adults, recent studies in patients with malignant gliomas, papillary craniopharyngiomas, and melanomas containing V600E mutations have shown excellent results, with 1one of several similar 2-drug combinations that target both the V600E mutation and a second pathway that cells use to escape from this BRAF blockade. Now, early pediatric data suggested that one of these pairs of drugs, the combination of dabrafenib and trametinib, was safe and tolerable and had the ability to effectively treat patients whose tumors had the V600E mutation. So with that as background, this study was started and enrolled patients from 12 months to 18 years of age who had a low-grade glioma that contained a BRAF V600E mutation. And it randomized them to receive either the combination of dabrafenib and trametinib, or an older, standard cytotoxic chemotherapy regimen consisting of carboplatin and vincristine. Importantly, these patients were newly diagnosed, and this was the first systemic treatment they got, following their surgery or biopsy. 110 patients were enrolled, with 73 given the new targeted therapy combination and 37 receiving the standard combination. The most common types of tumors that the patients enrolled on this study had included pilocytic astrocytoma, ganglioglioma, and low-grade glioma.

The results of this trial were that the patients who received the newer combination, targeted treatment of dabrafenib and trametinib, did substantially better than those who received standard, older cytotoxic chemotherapy. Their overall response rate - that's defined as a complete or partial disappearance of the tumor on MRI scan - was 47% versus 11% in the control arm. When patients who had stable disease by MRI were included, 86% of those on the new combination versus 46% of those patients treated with the older chemotherapy had the so-called best clinical response. Now, a large number of patients responding to dabrafenib and trametinib, remain on treatment and are receiving these drugs with an ongoing imaging and clinical response at the time of this report. Patients receiving the new combination had a median or average progression-free survival of 20 months versus about 7.4 months with the older, standard chemotherapy.

The investigators conducting this study also had patients fill out a variety of questionnaires to assess their quality of life while on treatment. Once again, the patients who received dabrafenib and trametinib, on average, experienced an improved quality of life in contrast to those on standard chemo who, on average, had a worse quality of life. The new treatment was also well-tolerated with fewer serious adverse events or side effects when compared with standard chemotherapy. And these side effects were no different than what has been seen in patients without brain tumors who have been treated with this combination, including fevers, headaches, fatigue, skin changes, and lower blood counts. The authors appropriately suggested that these findings demonstrate the importance of molecular testing of these pediatric low-grade glioma tumors at the time of diagnosis and that this combination of dabrafenib and trametinib is a new potential standard of care in those patients who have the BRAF V600E mutant, low-grade tumors. Of note, liquid formulations of these drugs have been developed for those pediatric patients who are unable to swallow capsules or tablets.

The second presentation at ASCO highlighted the continued importance of prospective randomized clinical trials in patients with malignant brain tumors. Dr. Jann Sarkaria from the Mayo Clinic presented the long-awaited results of the Alliance for Clinical Trials in Oncology cooperative group phase II/III study of a PARP inhibitor or placebo added to standard temozolomide and radiation in adult patients with newly- diagnosed glioblastoma, and in addition, glioblastomas that had specific molecular finding called MGMT promoter methylation. This change to the DNA of the tumors prevents the MGMT DNA repair enzyme from being made in the tumors and leads to a better outcome with temozolomide treatment. Some very elegant laboratory science had suggested that adding a type of drug called a PARP inhibitor, which also causes defects in DNA repair, could lead to improved killing of glioblastoma tumor cells. So patients with newly- diagnosed glioblastomas, which had MGMT promoter methylation on genomic analysis, were enrolled on this study between December of 2014 and October of 2018. The study was conducted in 2 phases separated by a pre-planned pause after the first group of patients were enrolled, which was the phase II part of the study. This was done in order to allow a preliminary analysis of the outcomes of the treatment arms to make sure that there was a signal of activity that justified moving on to test this treatment in a larger number of patients, the so-called phase III part of the trial. This trial design hopes to minimize the number of patients treated with an inactive drug and save years of drug development time by avoiding large trials that go on for a long time with what turns out to be ineffective drugs.

For this trial, 447 patients were eventually treated on this trial. Despite the convincing laboratory evidence and early, promising clinical results that led to the trial moving to the second or phase III portion, the final results showed no statistically significant difference in progression-free or overall survival between the 2 arms, that is, those treated with a PARP inhibitor, and those treated with placebo. I personally was very excited about this study and had hoped that the long wait to hear the results indicated that something good was happening. In addition, several of my patients who were treated on the study did exceedingly well, so I, incorrectly, it turns out, expected positive results from the trial. These negative results are a stark reminder of why we spend lots of time and money and energy performing well-designed clinical trials to determine appropriate treatment strategies for our patients, rather than relying on expert opinion or 1 institution's published experience. This approach turns out to be the best way to fairly test treatment strategies and establish new therapeutic approaches which are truly effective.

A final, interesting abstract that was presented at a poster discussion session at ASCO was from the group with the University of Pennsylvania in Philadelphia, and it dealt with the risk of bleeding in patients with brain tumors who had blood clots and were then treated with a newer class of blood thinners or anticoagulants called direct oral anticoagulants, or DOACs for short. It's been known for over 100 years that a variety of types of cancer cause patients to be hypercoagulable, that is, to be predisposed to developing blood clots throughout the venous system. Patients with malignant brain tumors have the highest incidence of all tumors of developing blood clots, which typically occur in the legs, called deep venous thrombosis or DVTs, or in the lungs, called pulmonary emboli or PEs. These clots can lead to a variety of severe and debilitating symptoms, including leg pain, swelling, shortness of breath, heart strain, and even death. For the past 2 to 3 decades, affected patients have typically been treated with a class of medications called low-molecular-weight heparins, which need to be injected under the skin once or twice daily. Over the past decade, a new class of oral anticoagulants called DOACs have generally replaced low-molecular-weight heparins as the primary method of treatment for patients with and without cancer who develop venous blood clots because of their safety, ease of administration, and a lack of requirement for regular blood tests or monitoring. However, little, if any, data has been available to determine the safety of these agents in patients with brain tumors and blood clots, a situation where bleeding into the brain or the brain tumor as a side effect of the anticoagulant could be catastrophic.

In fact, this potential risk led to the exclusion of patients with brain tumors from several of the large trials which established the safety of the DOACs. Despite the absence of evidence, the DOACs are now pretty broadly used in brain tumor patients for the reasons described above. So this abstract described a cohort of patients with glioblastoma who developed venous blood clots between 2014 and 2021 while under treatment at Penn. The authors reviewed the medical record to determine the relative efficacy or effectiveness and the toxicity or side effects experienced by patients treated with the low-molecular-weight heparins and with the DOACs, including the rates of bleeding into the brain or the brain tumor. 121 patients were identified who fit these criteria, and the cumulative incidence of clinically significant intracranial hemorrhage, that is, bleeding into the brain or the brain tumor, by 30 days after starting the drugs, was minimal and similar in the 2 groups. When measured at 6 months, 24% of the patients in the low-molecular-weight heparin group had developed intracranial bleeding, and 4 of those patients had died from this bleeding, while none of the 32 patients in the DOAC group experienced this complication. Thus, these investigators felt that their data suggested that there was a lower incidence of clinically important intracranial hemorrhage or bleeding in patients with glioblastoma and venous blood clots who were treated with DOACs as compared to low-molecular-weight heparin. They went on to suggest that the use of DOACs was a safe alternative in patients with glioblastoma. Now clearly, either a prospective trial, a larger trial, or additional retrospective evaluations with a larger number of patients are needed to prove the safety of this approach. But this data is pretty comforting, as the use of these agents is now widespread in patients with high-grade gliomas.

The ease of administration of a pill once or twice a day, as compared with potentially lifelong injections once or twice a day, is a major quality of life advantage for our patients. Thank you for listening to this brief summary of new research in neuro-oncology from the 2022 ASCO Annual Meeting.

ASCO: Thank you, Dr. Lesser.

Finally, Dr. Manali Patel discusses new research focused on reducing disparities in cancer care.

Dr. Patel is a medical oncologist and Assistant Professor of Medicine at Stanford University. She is also the Cancer.Net Associate Editor for Health Equity.

You can view Dr. Patel's disclosures at Cancer.Net.

Dr. Patel: Today I have the privilege of discussing several really exciting research abstracts that were presented at the 2022 ASCO Annual Meeting. My name is Manali Patel. I'm a thoracic oncologist, meaning I take care of patients and try to provide good care delivery for patients with lung cancer. And I also am a researcher focused on health equity. I have no relevant disclosures for any of the studies that I will be presenting today with the exception of one that I was leading.

And there were several wonderful abstracts that were presented on describing disparities and the ongoing state of disparities continuing within cancer care delivery. What I was particularly struck by were many of the abstracts that I'm presenting this morning and this podcast that really focus on what we can do as a nation and what we can do individually in our clinics to try to move towards action to overcoming these inequities. The first abstract I want to present was looking at how the Affordable Care Act and changes in the Affordable Care Act led to differences in mortality or deaths by race and ethnicity following the enactment in California. And this particular study looked at greater than 150,000 people who were diagnosed with breast cancer, colorectal cancer, and cervical cancer. And they evaluated death rates from these cancers both before and after the implementation of the Affordable Care Act. And what they found was that the cancer death rates for everyone was much lower after the Affordable Care Act was passed, but specifically for individuals who had self-identified as Hispanic ethnicity, who also identified as Black and who identified as White. And so what this abstract showed me was that at a larger level and a macro level, our policies that are enforced at the national level really do play a role in terms of how we can overcome disparities in cancer.

Our group, as I mentioned before, has worked on really trying to integrate community health workers into care. So this abstract paired with local union organizations in Chicago and in Atlantic City to try to help individuals who self-identified as having been from families that were from low-income households and racial and ethnic minorities to communicate their goals and their preferences for care and to also better their relationships with their clinicians as well as to describe their symptoms. And what we found in this randomized trial was that for individuals who received this community health advocate who helped them to better engage with their clinician and who also helped them to describe the symptoms that they were experiencing as well as receive community resources such as food boxes if they were food insecure or be connected to household agencies if they were having difficulties with housing, we found a significant improvement in quality of life, but we also found reductions in the use of the hospital unnecessarily. We also found that this translated into reductions in total cost of care, thereby reducing the amount of out-of-pocket costs these individuals were spending on their cancer care.

One of the other abstracts that I thought really was reflective of the many different ways that we can move towards action was an abstract which looked at during the pandemic, trying to reduce the number of times people need to come in for mammograms, their biopsies, and then any further testing that they needed after their biopsy. And this particular study evaluated what was called a same-day biopsy service, which layered on a same-day mammogram reading program. So at this particular institution, they had already implemented when you came in to get your mammogram as a woman or a man, you would have a read on the same day. So you did not have to wait to find out what your results were. And what they did further to push better care was that they layered on on that same day you could get your biopsy. So almost a one-stop shop. And what they found was that for everyone, regardless of race and ethnicity, the time to biopsies decreased by almost half. And the median days, for example, from an abnormal mammogram to obtaining a biopsy, meaning a sample of that tissue, that it decreased from 10 days median to 5 days. And particular patient populations did much better. And so they were able to show that when you do interventions that move the care to provide better care for everyone, everyone benefits, but particularly our patient populations who identify as racial and ethnic minorities who were more likely to experience delays in care, they also received some benefit from this intervention.

The last study I want to highlight is work which looked at how to improve specialized services for people who would otherwise not receive those. And this particular study looked at stem cell transplantation for people with blood cancers. And what they found was that these services are often only offered in very tertiary centers, so places that may not be as accessible, large institutions that a lot of people may not have access to receiving care. So what they did was they partnered with this large academic institution so that they could build a pathway for individuals who would otherwise not get stem cell transplantation so that they could have access to those services. And it was really a multipronged approach where they not only educated the clinicians in the community practice about the effort, but they also educated the institution-level clinicians about the effort. They also provided shared medical records, which oftentimes in practice, we don't share our medical records with other clinics. And what they were able to do was to convince these clinics and the institution, let's share the medical records so that then you can have access to seeing what's happening for patients that are diagnosed in the community. And then that way we can both document, we can both have access in the community as well as in the institution where they're receiving the specialized service so that there's better communication. They also provided a navigator for each patient that would help each patient to identify any sort of barriers that they may experience to receiving stem cell transplantation. And then they offered telemedicine, which allowed for individuals to receive specialized services in the comforts of their own home without having to travel after the stem cell transplantation had occurred. And what they found was that usually in the institution, most individuals were more affluent. So they had higher levels of socioeconomic status. But after the intervention, individuals that were referred from this community clinic made it such that the affluence really decreased so that it was showing that people who wouldn't otherwise have access, who had identified as having low income, were now able to receive those services and had been receiving transplantation.

I think that these studies really do move us towards a new paradigm of taking action on the many disparities that we know continue to happen. I really appreciate you all for listening to this brief summary of the new research on health equity from the 2022 ASCO Annual Meeting, and I hope to see you next year.

ASCO: Thank you, Dr. Patel.

You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today we're going to be talking about coping with the mental and emotional challenges of cancer through exercise. Our guests today are Dr. Sheila Lahijani and Sami Mansfield. Dr. Lahijani is an associate clinical professor of psychiatry and behavioral sciences at the Stanford University School of Medicine and the medical director of the Stanford Cancer Center Psychosocial Oncology Program. Dr. Lahijani is also an advisory panelist on the Cancer.Net Editorial Board. Thanks for joining us today, Dr. Lahijani.

Dr. Sheila Lahijani: It's truly my pleasure to be here today, Brielle, with all of you.

Brielle Gregory Collins: Thank you. Ms. Mansfield is the founder of Cancer Wellness for Life and the director of Oncology Wellness for the Sarah Cannon Cancer Institute at HCA Midwest Health. Thanks for joining us today, Ms. Mansfield.

Sami Mansfield: Thanks, everybody, for having me. Excited to be here as well.

Brielle Gregory Collins: Before we begin, we should mention that Dr. Lahijani and Ms. Mansfield do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to start, Dr. Lahijani, how can a cancer diagnosis impact a person's mental and emotional well-being?

Dr. Sheila Lahijani: Thanks for asking this question, Brielle. Usually, when people want to know the answer to this, what I preface it by saying is that there is a spectrum of responses. Many people find themselves to be quite distressed because cancer continues to have quite a lot of stigma, both in this country and as well as internationally. People oftentimes associate it with feelings of despair, anxiety, and helplessness. Having said that, many of these responses and reactions are normal. Some people can progress to have many more significant emotional responses and reactions that can become more disruptive to their lives and to the roles that they play a part in. We really try to meet patients where they're at to better understand how they've previously coped with past life challenges and/or traumas and to identify what strengths they have, what coping mechanisms they have to help them manage the distress associated with cancer. There are patients who also have a history of past psychiatric diagnoses and problems, in which case getting diagnosed with cancer and undergoing cancer treatment can cause a lot more difficulty. So each person is different. There are a lot of, quote-unquote, "normal" reactions, responses and reactions, that we as providers do validate and reflect back to the patients. And then there are those that can cause many more problems, and those are the ones we really need to address.

Brielle Gregory Collins: Okay. And getting into some of those problems, what are some of the most common mental and emotional challenges that people face during cancer?

Dr. Sheila Lahijani: The majority of people feel very anxious. And I've shared this with others and share this with my patients: being anxious means something. It means that you care about something. You care about yourself. You care about your life. You care about people in your life. And so it's a sign. It's something that needs to be tended to. People suffer from mood symptoms such as depression as well, difficulty coping, feelings of loss and despair. Those are the most common reactions. Some people can develop other difficulties related to side effects of cancer treatments as well. And also, there are people, as I mentioned, who previously have suffered from psychiatric symptoms, where things can become much more difficult and challenging, affecting their way of thinking: problems with cognition, memory, recall, things like that. So to summarize, largely mood disturbances and mood symptoms in the forms of anxiety and depression. Panic is also a part of that, as well as post-traumatic stress. And there are others who have previous symptoms that can become more problematic. So we really try to evaluate both mood and thinking in our patient population.

Brielle Gregory Collins: Thank you so much for walking through those. And I want to talk a little bit now about exercise and how that can play a role in coping with some of these challenges. Ms. Mansfield, what is considered exercise, and what are some of the benefits of exercising during cancer?

Sami Mansfield: Great question because there are so many different terminologies around exercise and physical activity and fitness. So I think we should start there. The terminology of physical activity is probably the most broad thing that we talk about. Physical activity is anything that we do to move the body, anything from rolling over in bed, getting up, brushing your teeth, etc. Exercise is a physical activity that is more defined or maybe has a purpose. And so it might be a goal to get stronger or a goal of rehab or prehab in this particular patient population. Or some people just want to be able to walk a 5k or run a 5k. So exercise is more intentional. And that's really how we try to define it in the literature.

From a cancer patient perspective, probably the most broadly impactful side effect management tool for exercise is actually fatigue because that is where we have a depth of evidence both in physical activity and inactivity differences. And related to fatigue from the mental health side, we see a strong benefit of both exercise and physical activity in anxiety, depression, stress management, sleep quality. So I think it's important for our audience to know that anything that you do for movement is good. Having a planned and structured movement program known as exercise is going to be ideal because the bottom line is we want you to reach your goal the quickest and without kind of feeling like you're not getting a lot of benefit to movement. And so that's why exercise really does have a significant role and why I think a lot of people really strive for, "What should I do? What does that specific exercise plan look like?"

Brielle Gregory Collins: Got it. And I want to circle back to some of the challenges, Dr. Lahijani, that you outlined earlier. So how does exercise help address some of these challenges of cancer specifically?

Dr. Sheila Lahijani: Well, I love this question. And I'm very informed by what my colleague, Ms. Mansfield, just described. Exercise and physical activity, in my opinion, are so beneficial to patients who are already diagnosed with cancer, as well as those patients who may be at risk for developing cancer-- any of us, really, to reduce our risk for certain kinds of cancer. There have been many studies that have been done that have demonstrated that intentional physical activity, as my colleague termed it, in the form of exercise can ramp up certain biological processes that contribute to improvements in cognition as well as memory function. There's a factor called a "brain-derived neurotrophic factor" which can get increased with physical activity and exercise. At the very molecular level, muscle cells can play a part in reducing the progression of disease and even potentially metastases. So there's a lot to be said biologically. As well as psychologically, it really can offer quite a lot of benefit to help people manage their distress through focusing on momentary breathing, momentary muscle relaxation. And there is also a social component to it. Even if someone is participating in an activity like this by himself, herself, or themself, there is something to be said about the communal experience of being up on your feet, moving yourself, and not being so isolated and alone, which is very much a problem for patients who undergo cancer care.

Brielle Gregory Collins: That's a really good point. And Ms. Mansfield, I want to get a little bit into the specific things that people can do. So what kinds of exercise can help people with cancer cope with these challenges?

Sami Mansfield: Now, it's a great question because that's what everybody wants. What should I do, right? And I tell everybody let's just start, number 1, with avoiding as much true sedentary behavior as possible. And I say true sedentary behavior because when you are just sitting and doing perhaps mindless activities, watching TV, there's a lot of exercises that can be done when you're seated, which is great for patients that have high amounts of fatigue or balance challenges. And I tell everyone, "Lift an arm. Lift a leg. Flex your toes and feet a couple of times, roll your shoulders, and you've just moved." It doesn't have to be vigorous or difficult. It just needs to be movement. So I think just thinking about these 1-minute, we call it "exercise snacks," make a much more significant impact throughout the day than feeling like, "Oh, I've got to go to the gym and exercise for 30 minutes," or you might even have physical therapy. And the volume might be too high for people. So I want people to think first in small 1-minute movements.

But the next piece of this is, we've studied the different modalities of exercise between aerobic exercise, thinking about things like walking, or chair-based, like marching in the chair, swimming, biking, whatever that may be. And resistance training exercises that use muscles. You could do something with weights, soup cans. You could do bodyweight exercises that build muscle. We've studied them separately and together. And what we've learned is that for the emotional side effects, specifically anxiety, depression, having a combination of these movements is going to give you the most significant benefit. So my advice is do a minute of marching, whether that's in your chair or standing, then maybe do a chair sit-to-stand 10 times and a couple of countertop pushups, and you've now hit a full-body routine exercise regimen in under 5 minutes. I do think that people need to remember although there are recommendations of how much you should strive for, there's no reason you have to do the whole recommendation of 150 minutes of moderate activity per week to see benefit. Start with just 1 minute at a time, 1 movement at a time, and try to mix it up. Make it fun. Add music. Make it a challenge. Make it something that you feel that you can attain because you will feel better and also accomplished. And that does improve your well-being, to feel like, "I did that. I did my 1 thing a day." And that's really phenomenal and goes a long way to how people feel mentally.

Brielle Gregory Collins: Absolutely. And I love that term you use of "exercise snacks." I think that's a really helpful way of looking at it. So for someone who's maybe just getting started with exercise, what is your advice for them as they manage their cancer diagnosis and are trying to look toward exercise as something that they want to incorporate into their lives?

Sami Mansfield: That's definitely the question I love to answer. Because if somebody's motivated, we want to get them there quickly or get them to find a resource that helps them feel successful. I kind of go back to the whole "exercise snack" piece. I think it's more important that people realize it's better to do a little something every day than to think, "Oh my gosh, I need to hit 30 minutes today, and then for the next 3 to 5 days, I don't do anything." I really advise start small, start manageable, and look for something that you can do without having to add extra barriers to your life. As an example, if getting somewhere logistically on time doesn't work for you, start with 5 minutes of things that you can do from your home. I do think there is a really important resource within most of our cancer spaces. We have oncology rehab programs. We have trained exercise professionals that can guide you. But I think people don't realize that just moving around their house, maybe 1 flight of stairs if you can do that, is a really great way to get started. There's a lot of great YouTube videos you can try. There is definitely—talk to your physicians. They might have some great ideas. But starting daily, consistency really is going to make the biggest difference than just going, "Hey, Saturday is my day to exercise." I think we can all do a little bit in that snack fashion. And I don't know. I think we can all agree snacks are good. We all like a few snacks now and again. Definitely.

And I also kind of have this thought about-- people say, "Well, if they have cancer, should they do yoga?"   And my answer is, "Well, do you like yoga?" I mean because yoga has a lot of really great resources for mental health and breath to movement and mindfulness and that grounding effect. But for someone who doesn't like yoga, which I will admit yoga is a little bit of my challenge so I push myself to do it, someone telling me to do yoga every day versus maybe exercises that I enjoy, I would be a little bit more down in the dumps about it, that you're taking away maybe what I love. So I think 1 thing, really thinking about what's the type of exercise you like to do, is it reasonable for you to continue that? If you used to run and maybe you have a lot of neuropathy in your feet, it might not be the most reasonable now. But what is the exercise that you enjoy? And that should also be part of that first thing that you do every day, not your, "Well, someone told me I should do yoga because they enjoy doing yoga," piece. And I think that's something that we need to think about in exercise. It still should be enjoyable and have good music. I think music is key as well.

Dr. Sheila Lahijani: I think it's really important to highlight as well that cancer causes so many life disruptions: disruptions to different roles, activities, functions, whatever it may be. And in speaking about intentional physical activity and exercise, it's an opportunity to create a routine and to try to lessen the impact that's caused by the disruptions.

Sami Mansfield: The pandemic certainly accelerated that for those of us who don't even have cancer. I don't know if anybody here also experienced this.  But I remember I was working out in a gym setting-- and we actually had our own-- we ran a gym space at the time in Kansas City for cancer survivors. So we took that virtual. But I struggled with my routine. I was like, "Wait a minute." And I could go to my own gym that was private, right? But I really struggled with the mentality of like, "It wasn't my routine." And when your routine slips, you just feel very out of control. I think 1 recommendation we should make for all of our listeners, physicians, or those of us that are working in the field is I recommend starting every day with a minute of movement. I don't care if you're doing a few arm circles where you're waiting for your coffee or whatever, but there is something about getting your blood flow moving quickly that makes a really big difference. So whether that's, "Before I brush my teeth, I'm going to just do a couple of leg swings or a couple of countertop pushups or something simple every single day." Or if you're in bed, you do something in bed, even if it's just your foot flexion or drawing the alphabet where you're doing something to stimulate movement." You bring up a really good point, that we need to make that ritualization or routine, but make it also very accessible for people.

Brielle Gregory Collins: Absolutely. Thank you, Ms. Mansfield. That's really helpful. And Dr. Lahijani, in addition to exercise, what else can people with cancer do to cope with some of the mental and emotional impacts of their diagnosis?

Dr. Sheila Lahijani: Thanks for asking this question. And I want to also preface this by saying so much of what we're talking about is essentially what is now a field of exercise oncology, right? And so there's more and more literature available and resources that emphasize the benefits of exercise in this patient population and how the effects of other treatment modalities, such as antidepressants and psychotherapy, can be further enhanced when someone is also being physically active or having an exercise snack. So to answer your question, what I'm saying is there are many ways we can support our patients and many ways we can encourage them to have better management and control over their distress-- why there is anxiety, depression, sleep disturbances. It's really meeting people where they're at-- which Ms. Mansfield also mentioned, starting somewhere.

So when we see patients in our clinic-- and I've been known to do this, and I've done this back in the day where we would really write a lot more paper prescriptions. But even as part of my discussion points and patient instructions, I always make a point of writing, "Do some physical activity, even minimum opportunity to get yourself moving." Because what we're trying to really do is help with the circulation-- help with the circulation in the body, in the brain, really ramp up those neurotransmitters that help people feel better, remove the unhealthy oxygen, introduce the healthier oxygen. And that, in conjunction with medications, in conjunction with different psychotherapy modalities, in conjunction with progressive muscle relaxation, mindfulness, grounding techniques, can really help people feel less helpless, less stuck, less tired-- again, as I mentioned earlier, less alone, and find opportunities where they have more of a sense of control because that's part of what we're talking about here. There's a strong feeling of helplessness and lack of control when someone is diagnosed with cancer and undergoes cancer care. And this is an opportunity to help them find ways to manage their health physically, mentally, cognitively, spiritually, and feel less a sense of helplessness.

It's really encouraging me to say that there are many patients who are physically really suffering, whether it's from neuropathic pain, cancer-related fatigue, any kinds of deconditioning related to surgical interventions, other effects of chemotherapies, from depression. And it is much, much harder. And people sometimes cannot physically move. And it requires a lot more activation energy to take those steps. So part of what we do in my clinic and how we partner with our colleagues in palliative medicine as well is how can we manage people's symptoms? How can we manage their depressive symptoms, their physical symptoms? How can we help them be more cognitively stable and intact to be able to safely take those steps or to have more of that motivation or that energy or that pain relief to be able to participate in the things that we're talking about? I'm cognizant of the fact that when we have our patients and family members and caregivers listen to this, there may be some folks who are like, "But I just can't." And I have patients who tell me, "I get it, Dr. Lahijani. I understand. And I appreciate this guidance that you've offered me and the recommendations to use this medication or to consider this, but I just can't." So that problem with motivation and lack of optimal symptom management really has to be addressed in parallel, in my opinion, to really help support patients in actually participating in what we're suggesting here.

Sami Mansfield: I think that's not only an excellent point, I think you really reiterate the partnership that needs to happen with the clinicians and the exercise oncology field or oncology rehab field because the only way to really do this effectively again, and especially a more complex patient, is in conjunction with one another. And I think that we need to be mindful and remind the patients, and like you said, the family members listening, that the conversation should be had, but the clinicians really can help manage the clinical symptoms so that the exercise or rehab professionals can really get in with that, the more implementation piece, when reasonable. But I think we need to take the guilt off our patients that it's not going to be every day, even though they want to. And that's the reality, and that is okay. And some days, it is a rest day or a rest week. And that is part of the healing process of the body and a really important way to recover. And that's okay, too. I think recommendations are nice as an example. But at the end of the day, if they're not reasonable for people, we need to also take that next layer of guilt away. And they just need to be able to feel comfortable and pain-free and symptoms-managed. And that's quality of life as well.

Brielle Gregory Collins: Wow, what a great discussion. And I think the main takeaway here for anyone listening is your health care team is there to help you, and they'll work with you to figure out what's best for you, whatever that might be. So thank you so much. That was wonderful to hear both of your perspectives. And I want to talk a little bit about resources that people listening can turn to to learn a little bit more about this. So I'd like to direct this to both of you. Ms. Mansfield, we'll start with you, but where can people go to learn more about exercise and managing the mental and emotional effects of cancer?

Sami Mansfield: Absolutely. That is the key question is, what next? Really, Cancer.Net is a wonderful and evolving resource and is continuing to progress its information. So no matter when you're listening to this podcast, check out Cancer.Net. I know that the information is online. There's a ton of resources right there. There are some other really great programs and resources. I would talk to your clinicians about things like cancer-specific rehab programs that you may have access to, which many have insurance coverage. And I tell people you don't have to feel broken to get cancer rehab. There are a lot of ways that cancer rehab can help you even just manage general fatigue or cognition. Referral to a speech-language pathologist can be helpful with some of those techniques about memory and chemobrain. So those are resources. In addition, there are qualified exercise professionals through the American College of Sports Medicine that have training and certifications and have experience. That can be another resource that can help you. I would also advise people to think, "You don't always have to have a cancer professional." There are great fitness professionals that may fit-- yoga professionals or other types of exercise modalities. So don't always feel like you have to find the "cancer person." But depending on your symptoms or side effects, having a professional that understands what it means when you say neuropathy can be very helpful. So I would definitely start with those resources first and then branch out as you feel comfortable.

Dr. Sheila Lahijani: She responded to that question beautifully. And to add to what she just shared, looking at what your own cancer center, your place of health care where you receive it, what's available. There are many websites through the different cancer centers and medical centers that have wonderful patient-facing and family-facing educational resources. The American Cancer Society also has a lot of helpful information. As Ms. Mansfield mentioned, Cancer.Net is a wonderful resource. And also to emphasize that there are programs that can be done virtually, especially in this era of this pandemic. While we encourage in-person interactions, however it's safe and feasible because there's so much benefit to feeling less alone and isolated and maybe having that direct 1-on-1 attention, we recognize that many patients because of their immune compromise or because of whatever challenges they may have with respect to support or transportation or finances, whatever it may be, it might be harder to access care or services where someone lives. And so there are programs and services that are available online. And that shouldn't be limiting. That should be something to really think about and consider.

Actually, I was in a meeting recently where I learned about an organization called the Maple Tree Cancer Alliance, which has programs available through different cancer centers as well, among which is my center, Stanford. And so there are plenty of resources available. And with that, I will also say pick something. Choose something. You don't need to look at everything and try to do everything. Take a look at what's available to you, what's accessible to you, what makes sense, and just try it out, and see if it helps. And if it doesn't help or if it's not providing you any kind of immediate benefit, look to see what other options there are. We have so many patients tell us that they're trying to follow through on our recommendations, and people want to be, quote-unquote, "good patients." And that can get very overwhelming. People in large part want to feel better. They want to get better. That doesn't mean you have to take advantage of every single resource or recommendation that's being offered to you. Take a look at what's close to you, what you can access, and how you can make it work, and start somewhere.

Brielle Gregory Collins: Absolutely.

Sami Mansfield: And on that start somewhere, the other thing to really think about too - and Dr. Lahijani really said this - is you don't have to do-- everything at once can be so overwhelming. This is the long game. And so this exercise piece should be a lifestyle behavioral change piece that works for you in the long-term. It isn't about just, "Here I am. I want to get through just this 1 specific piece in my life." Look for something that you enjoy because you're going to be much more likely to continue. And then thinking about that support circle, it may be someone that has a similar diagnosis or understands what you're going through or have gone through. And it may be somebody that you have met or a family member that has never experienced this but is that person that you can vent to or is your accountability partner or your meet-for-a-walk or a virtual walk partner. I think we need to be really mindful, be creative about this. It should be enjoyable. It should be something that fits you. And at the end of the day, there's no right way to exercise. I think we'd all do something different here today if we all could choose. And that's okay too. Cancer is very individual, and so is this piece of that. So I think that's really empowering for all of our listeners to remember.

Brielle Gregory Collins: Definitely. And that's so nice to hear, as far as there's no right way to exercise, I think that's a really helpful way of looking at it. Well, thank you both so much for your time today and for sharing your expertise, Dr. Lahijani and Ms. Mansfield. It was so great having you both.

Sami Mansfield: Thank you so much for having us.

ASCO: Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

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The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in multiple myeloma, breast cancer, and cancer in adults 60 and over that was presented at the 2022 ASCO Annual Meeting, held June 3-7.

First, Dr. Sagar Lonial discusses a study on treatment for newly-diagnosed multiple myeloma in people under 65.  

Dr. Lonial is a professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University, where he also serves as Department Chair. He is also the Cancer.Net Associate Editor for Myeloma.

View Dr. Lonial's disclosures at Cancer.Net.

Dr. Lonial: Hello, I'm Dr. Sagar Lonial from the Winship Cancer Institute of Emory University in Atlanta, Georgia. And today I'm going to discuss one of the Plenary abstracts at ASCO 2022, which was the DETERMINATION study, again, presented at the ASCO Annual Meeting. For the sake of disclosure, I just want to make sure I list that I was an investigator on this study. I also have consulting relationships with Takeda, Celgene, BMS, Janssen, and other companies that have agents in the context of multiple myeloma.

So the reason I want to talk about this study today is I think it's a really important study that was designed over a decade ago to really ask the question, with a really powerful induction regimen that uses what we now call the RVd regimen, lenalidomide with bortezomib and dexamethasone, do you really still need to have high-dose therapy and autologous transplant as part of the treatment approach?

And so the trial was a very simple randomized trial that everybody received RVd induction. And then there was a randomization between early transplant and then going on to consolidation and continuous lenalidomide maintenance versus no transplant going on to consolidation and lenalidomide maintenance. So both arms actually received continuous lenalidomide maintenance, which is really one of the important endpoints of this study overall. And the reason I say that is there was a smaller study done in France a few years previous to this where patients only received 1 to 2 years of lenalidomide maintenance. And in that trial, clearly the use of transplant was better. And the remission duration for the group that received the transplant was about 48 months. So the question was, with continuous lenalidomide maintenance, can you make that longer?

So randomized trial, over 600 patients were randomized between these 2 arms. And the follow-up now is somewhere around 7 years in total. And what was demonstrated both in the ASCO Annual Meeting as well as in the paper that came out at the same time in the New England Journal of Medicine was that the remission duration was clearly longer in the group that had the transplant than the group that did not, even with both arms receiving continuous lenalidomide maintenance. And it was almost 66 months in the group that received the transplant, 21 months longer, almost 2 years longer than the group that did not receive the transplant. And so I think this is really important because what it says is that even in an era of really good induction therapy, transplant continues to offer significant benefit in terms of progression-free survival.

Now, the reason progression-free survival is so important in this study is that we know that no time is more sensitive for treatment of myeloma than that first time we treat the patient. And so prolonging that first remission is really important because the disease is at its most sensitive at that time point. Now, there were questions about overall survival. Should we see an overall survival benefit? And I'll tell you, A, this trial was never designed to measure an overall survival benefit. And, B, the median survival for myeloma patients is now between 10 and 15 years on average. And so with only 7 year follow-up, it seems to me unrealistic to expect this to have a survival benefit at this early time point. So rather than saying there's no difference in overall survival, I think it's a fair statement to say at the short follow-up we have, there is no difference in survival. But I actually don't think survival is the right endpoint for newly diagnosed myeloma trials in fit patients because we do have so many important treatments to discuss.

Now, there was also discussion about adverse events. Obviously, the quality of life during the transplant dropped a little bit. Not a big surprise. That lasted about 2 to 3 weeks, and then quickly, by 3 months out, returned back to baseline for almost every patient in the study. Additionally, there was a concern about second primary malignancies. If you look at this data, it's really no different than what we saw in the French study. There was a slightly higher risk of second primary malignancy, but we know that this is the case not only in myeloma, but in patients who receive alkylate-based therapy. And despite that, the progression-free survival was 2 years longer in the group that received the transplant than the group that did not.

So I think, in summary, this is really an important trial because there are many groups that are making the case that perhaps we don't need transplant in this modern era of myeloma therapy. And I think that it's important to recognize that what we're looking at are not short-term endpoints. We're not looking at early MRD (minimal residual disease) negativity. What we're looking at is really ultimate measurement of clinical benefit, which to me is prolonging that first remission as long as you can. And so this trial clearly demonstrates that for young, fit patients, transplant continues to offer significant benefit, almost 2 years of benefit with continuous lenalidomide maintenance. And while there's a push to say perhaps we can think about which patients may or may not need a transplant, honestly, as clinicians, we're not good enough to make that prediction. And what I think is really important is that we not lose sight of trying to prolong that first remission with the best tools that we have. And I think even in this modern era of 2022, high-dose therapy and autologous transplant continues to be one of those tools, and we want to use it to maximize the duration of that first remission. So thank you again for listening to this brief summary of the DETERMINATION trial presented at the 2022 ASCO Annual Meeting and published in the New England Journal of Medicine.

ASCO: Next, Dr. Norah Lynn Henry discusses new treatment advances for people with metastatic breast cancer, as well as 2 studies in early-stage breast cancer.

Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the Cancer.Net Associate Editor for Breast Cancer.

View Dr. Henry's disclosures at Cancer.Net.

Dr. Henry: Hi. I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates in breast cancer from the 2022 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both metastatic and early-stage breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We typically treat those cancers first with antiestrogen treatments, which block estrogen or lower estrogen levels. Other breast cancers are called "HER2 positive." These are often more aggressive cancers, but because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or very much HER2. These are called triple-negative breast cancer and are also often aggressive cancers.

One of the biggest stories from the ASCO Annual Meeting was the results of the DESTINY-Breast04 trial. In this trial, researchers studied a type of medication called trastuzumab deruxtecan, which is also called Enhertu. This drug is a combination of the anti-HER2 antibody, trastuzumab, plus a chemotherapy drug, and the antibody targets the drug to the cancer sort of like a guided missile. Trastuzumab deruxtecan is currently routinely used to treat patients with metastatic HER2-positive breast cancer. Now, the interesting thing is there was already data from studies that suggested that this drug might also work against breast cancers that have some HER2 receptors on the surface of their cells, but not so many that they meet the true definition of being HER2 positive.

For the DESTINY-04 study, patients' tumors had to have either 1+ or 2+ HER2, which some people called "HER2 low," and could be either estrogen receptor positive or negative. Two thirds of the patients were treated with trastuzumab deruxtecan, and the other one-third were treated with 1 of 4 different standard chemo regimens that their physician thought was the best treatment option for them. Treatment with trastuzumab deruxtecan was shown to lengthen the time people were able to remain on treatment. Importantly, it was also shown to increase the overall survival of patients compared to standard chemotherapy by more than 6 months for patients with estrogen receptor-positive cancer and by more than 10 months for patients with estrogen receptor-negative cancer. Since this is a drug that we currently use to treat patients with other types of cancer, we actually know a lot about its side effects. One key toxicity is it can cause a very severe inflammation of the lungs in a very small subset of patients. So this is something that we have to watch for very carefully. Otherwise, it is a relatively well-tolerated drug, especially compared to standard chemotherapy. The main side effects are nausea and fatigue.

Another clinical trial presented at ASCO called TROPiCS-02 also studied a drug that is currently used to treat a different type of breast cancer. In this case, the drug is sacituzumab govitecan, also called Trodelvy. It is also a combination of an antibody that is targeted against cancer cells plus a chemotherapy drug. Sacituzumab govitecan is currently approved to treat metastatic triple-negative breast cancer.

In the TROPiCS-02 trial, however, it was tested to see how effective it is for treating hormone receptor-positive, HER2-negative metastatic breast cancer. All of the patients enrolled in this trial had already been treated with antihormone therapy medications as well as at least 2 chemotherapy regimens. Half of the patients were randomized to treatment with sacituzumab govitecan, and the other half were treated with 1 of 4 standard chemotherapy drugs that their physician thought was the best for them. Those patients who were treated with sacituzumab govitecan had a longer time on average that the treatment worked compared to those who received standard chemo. They also had improved quality of life based on responses that the participants themselves provided on questionnaires. Although the overall benefit was rather modest, this drug may represent a new treatment option for patients with hormone receptor-positive, HER2-negative metastatic breast cancer, although at this time it isn't yet approved for treatment of this type of breast cancer. Both of these are examples of being able to take drugs that have been shown to treat 1 type of cancer and potentially expand it so that they can be used to benefit more patients with breast cancer. These drugs are also being tested to see if they are beneficial for treating early-stage breast cancer. So we await more hopefully very exciting results in the future.

To switch gears a little bit, I'll now talk about another study I found interesting. This one is in the setting of early-stage breast cancer. So typically, radiation therapy is recommended after lumpectomy since it reduces the likelihood of cancer returning in the breast. However, questions have arisen about how much benefit radiation is actually providing for some patients whose risk of having cancer return in the breast is really low to start with. Therefore, these patients may be at risk of the side effects of radiation as well as other risks, such as financial problems, without actually getting much benefit from the treatment.

Therefore, this trial, called LUMINA, evaluated whether radiation therapy was beneficial after lumpectomy for patients who have small, low-risk breast cancers and no lymph node involvement. The trial included 500 women who were at least 55 years of age with invasive ductal cancers that were no more than 2 centimeters in size. They had to be estrogen receptor-positive, HER2-negative, either grade 1 or 2, and Ki-67 low. Everyone had to be planning to take antihormone therapy for at least 5 years. During the 5-year follow-up period, a total of 10 patients out of 500, about 2.3% of all patients, had their cancer return in the breast. The researchers therefore concluded that for patients with this type of very low-risk breast cancer, it is reasonable to omit radiation therapy and just take endocrine therapy. Similar results have previously been shown for patients over the age of 70 with small lymph node-negative low-risk cancers, but this trial expands that option to patients who are as young as 55.

Finally, I will touch briefly on the updated results from the ABCSG-18 clinical trial. So this trial enrolled postmenopausal women with early-stage estrogen receptor-positive breast cancer who are being treated with aromatase inhibitor therapy. Aromatase inhibitors are known to cause reductions in bone density. This trial therefore evaluated a medication called denosumab, also called Prolia, which is used to treat osteoporosis. Participants were randomized to treatment every 6 months with either denosumab or a placebo. They found that the patients who were treated with denosumab were half as likely to have a bone fracture. Importantly, patients treated with denosumab also had an improvement in bone density despite taking the aromatase inhibitor medicine, whereas those who received placebo had a decrease in their bone density over time.

The other very interesting thing from this study is that patients who received treatment with denosumab were less likely to have their breast cancer return or to develop a new cancer during the 8-year follow-up period. So it's actually already recommended that postmenopausal patients with all types of early-stage breast cancer consider treatment with a different type of bone strengthening medicine called a bisphosphonate as part of their breast cancer treatment. The goal is to further reduce their risk of cancer returning. These new results will now lead experts to debate whether to also include denosumab as a potential additional breast cancer treatment option, not just to help protect people's bone density.

There were a lot of other research findings presented that were related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, and we eagerly await the results of large, randomized trials so that the drugs that work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2022 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you.

ASCO: Thank you, Dr. Henry.

Finally, Dr. Shakira Grant discusses 3 studies that looked at cancer in people 60 or older. This field is also known as geriatric oncology.

Dr. Grant is an Assistant Professor in the Divisions of Hematology and Geriatric Medicine at the University of North Carolina at Chapel Hill and a board-certified Geriatric Hematologist/Oncologist.

View Dr. Grant's disclosures at Cancer.Net.

Dr. Grant: Hi, everyone. I am Dr. Shakira Grant. And I'm an assistant professor at the University of North Carolina at Chapel Hill. I'm also a clinician scientist with a focus on social disparities and how they influence the health and aging of older adults with cancer, primarily multiple myeloma. And for today's talk, I have no relevant conflicts of interest to disclose.

It's such a pleasure to be able to talk today about the ASCO 2022 geriatric oncology and presenting key studies, which I believe were really practice-changing or really set up the foundation for informing future research directions. And to start us off, I wanted to start us with abstract 12012 by Dr. Mackenzie Fowler. And this was presented based on the University of Alabama at Birmingham's actual research group. And the title of their presentation was "Rural-Urban Disparities in Geriatric Assessment Impairments and Mortality Among Older Adults with Cancer." And this was the result of a large registry study, predominantly patients with gastrointestinal cancer-- so cancers such as liver cancer, colon cancer. And what the authors really wanted to do here was to explore if whether or not living in a rural location, for example, is associated with having an impairment based on what people report in their ability to function at home, their quality of life. And they also wanted to see whether or not where you live, meaning a rural location, whether that can be associated with how long you are expected to live or your overall survival.

So this was really a study that took patients who were truly older. There were patients who were above the age of 60. As I mentioned, these were patients predominantly with cancers of the liver, the colon, and the pancreas. And patients completed a baseline, what we call a geriatric assessment, to try to assess their overall or global health. And on these assessments, patients are asked questions about how they would rate their physical function and their quality of life. And what the authors found here is that in general, when patients lived in rural areas, this was associated with patients self-reporting more functional deficits, meaning that they reported that they had impairments in the ability to function at home from a physical perspective. They also had impairments in quality of life—so how you rate your general life and how you're doing from a day-to-day basis. And this was impaired if you lived in a rural residence. And then, importantly, this study also showed that living in a rural location—and, again, this study was centered in Alabama—that that was also associated with a reduced overall survival, meaning that people were found in rural areas to live a shorter life with these cancers compared to those who live in non-rural places or, as we call it, urban.

And I think why I chose this particular study is because it's one of the first studies using a large data set of almost 1,000 patients that they have enrolled and really looking at the idea of the physical environment, so where a person lives, and how that really interacts with everything else to influence the health of an individual. And this study, I believe, really lays the foundation for an area of work in geriatric oncology where we are moving away from just thinking about the older adult, but we're also thinking about the older adult and the other identities. So we're really considering the sociocultural influence. So we think about race. We think about socioeconomic status, income. But now, we're also including the physical environment. And that is where people are living and spending the majority of their time. And that is in this study classified as rural-urban residency. So for this study, overall, I would say that this is really moving the field forward in a direction where we're moving away from just looking at just older adults, but we're thinking about older adults and all of the other stressors that they face, especially when they live in the community and how that impacts their health.

The next study that I wanted to highlight was a study that was performed by Dr. Heidi Klepin at Atrium Health, Wake Forest Baptist. And this was a study that looked at evaluating the association between an electronic health record-embedded frailty measure and survival among patients with cancer. Again, this was an older adult population. It was just over 500 patients involved, and patients were over the age of 65. They had a new diagnosis of the most common cancers, which are lung cancer, colon cancer, and breast cancer. And the good thing about this particular study is that it sought to use data that is readily captured in the electronic health record to characterize a patient as fit, prefrail, and frail. So why is that important for the geriatric oncology community and even beyond is when we're dealing with older adults, we're always thinking about ways in which we can actually characterize their fitness and their ability to hence tolerate their therapies, being chemotherapy, and how likely they are to die if they're having these functional impairments.

And so importantly, what this study showed was that in their sample, they found that up to 17% of people were characterized as frail using this index. And the significance of this finding is that when they looked at how long people were likely to live with these cancers, breaking it down according to if you were fit, prefrail, or frail, those who were frail had the shortest overall survival. So it means the time from which they were diagnosed until they die was much shorter than any of the other categories. And that equated to a difference between those who were fit and those who were prefrail of 10 months for those who were frail for overall survival and more than 54 months for those who were actually considered to be fit. So this is really, really important because what we are seeing is that if you are really fit, you are living on average with these cancers—the overall survival, at least for their institution, was more than 54 months. But then as you move across that spectrum of fitness, we're actually seeing that your survival decreases significantly.

And so why is this important? So this is important because it's one of the first studies that is actually looking to operationalize the frailty measure for us to be able to potentially use and adapt into other health systems using data that we already collect. So it's no longer burdensome on patients to try to fill out additional forms or for other staff to be involved and collect this data. And this data is showing us that there is an association with this particular frailty index and the ability to predict overall survival-- so, again, a critical study in the geriatric oncology population looking at patients with the 3 most common types of cancer, which are lung cancer, colon cancer, and breast cancer, and really showing us that there is a way potentially to operationalize how we characterize the fitness level of an older adult and then using that data not just to say, "Yes, this person is frail," but for us in real-time to see results where we can see that there is a significant difference in terms of overall survival.

Importantly, this is going to be a study where we continue to watch closely the developments over the next few years, especially as the authors and the research team note that their next steps involve looking at how to study how these frailty measures, or the frailty scores that people get when they come in and they're at baseline, how this changes throughout the course of treatment. And that has a lot of implications because now, we have the potential to start thinking about using a frailty-adapted approach to caring for older adults with cancer. What that means is when you're getting your treatment and we are following these scores, as we see things changing, this may be an indicator to us that, "Hey, we need to make some modifications in response to these frailty measures to make sure that our older adult population is able to tolerate their chemotherapies and have maximum benefit while also enjoying a good quality of life."

So finally, I want to highlight this third study. And this was a study that was presented by Dr. Etienne Brain. And. Dr. Etienne Brain was also this year's B.J. Kennedy Award recipient. And each year ASCO recognizes the B.J. Kennedy Award recipient as an outstanding investigator who has made significant contributions in the area of research and clinical care of older adults with cancer. In this particular study, Dr. Etienne presented on behalf of his team the final results from a study that was looking at using endocrine therapy with or without chemotherapy for older adult women, so characterized as those who were over the age of 70, with a diagnosis of estrogen receptor-positive, HER2-negative breast cancer. And the importance for this study is that the question they sought to examine was whether or not patients who are in this age range still derive a benefit from receiving chemotherapy in addition to endocrine therapy.

And what this study really showed is that there was no survival difference. Meaning when they looked at the data for 4 years, those who got chemotherapy plus endocrine therapy lived just as long as those who also just got endocrine therapy alone. And why this is important is because when you think about giving chemotherapy to an older adult population, as oncologists, we are always weighing the risks and the benefits associated with treatment. So we're always thinking about how tolerable is this drug likely to be? We want to minimize side effects because, at the end of the day, our goal is to treat the cancer, but we also want to focus in on the outcomes that matter most to the older adult population. And in general, these are things like maintaining your mobility, maintaining your mentation, maintaining good quality of life. And so we really want to make sure that we're balancing those risks. And this is why this particular study showing that with chemotherapy or without chemotherapy added to endocrine therapy, there seems to be no survival difference. This could be a way in which we move the field forward in thinking about a select group of patients with breast cancer and whether or not those patients truly need that extra toxicity or burden associated with using chemotherapy or whether endocrine therapy is enough.

So with that, I will say across these 3 studies, even though they study different things-- we saw 1 study that looked at the intersectionality between older adults in terms of their chronological age but now starting to examine the influence of physical or social context and how that influences the health and outcomes for individuals with primarily gastrointestinal cancer. We also looked at the development of an electronic frailty index in patients with 3 most common solid tumors - lung cancer, colon, and breast cancer - and found that by using this frailty index collecting readily available data, that there was an association with predicting overall survival. And we saw that those who were characterized as frail had one of the shortest overall survivals. And then finally, in this study, looking at endocrine therapy alone versus chemotherapy and endocrine therapy, we saw that there was no survival difference again in an older adult population. And so what we are seeing here is a theme emerging as the importance of comprehensive evaluations of older adults and the importance also of these measures, when integrated across the research continuum, that they are useful in terms of predictive prognostic abilities and really lay the foundation for future research. So with that, I want to thank you for your time and thank you for listening.

ASCO: Thank you, Dr. Grant.

You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. 

The beginning of the COVID-19 pandemic brought with it confusion, fear, and uncertainty for most people around the globe. These feelings were often heightened for people with cancer as they experienced disruptions or changes in care, such as following greater safety precautions at their treatment centers, having their appointments shifted to televisits, and facing delays in recommended cancer screenings. 

As a response to the COVID-19 pandemic, Cancer.Net developed several resources for people with cancer, including its post "Coronavirus and COVID-19: What People With Cancer Need to Know," written by Dr. Merry Jennifer Markham. After publishing this post on March 3, 2020, Dr. Markham reviewed and updated the post for 650 days straight to make sure people with cancer were receiving the most up-to-date and relevant information about COVID-19. The post went on to receive the Award of Distinction from the eHealthcare Awards in the Best COVID-19 Pandemic Related Communications category and was translated into Spanish, Portuguese, Russian, and Arabic. 

In this podcast, ASCO's Chief Medical Officer, Dr. Julie Gralow talks with Dr. Markham about her role in creating information for people with cancer throughout the pandemic, how the pandemic has shifted her perspective, and where she sees the future of the pandemic response headed.

Dr. Gralow: Hello. I'm Dr. Julie Gralow, ASCO's Chief Medical Officer. Today, I'm talking with Dr. Merry Jennifer Markham, an ASCO volunteer and the Cancer.Net Associate Editor for Gynecologic Cancers. Cancer.Net is the patient information website of ASCO. Dr. Markham is also chief of the University of Florida, Division of Hematology and Oncology, a clinical professor in the University of Florida College of Medicine, and the associate director for medical affairs at the University of Florida Health Cancer Center.

Dr. Markham played a key role in ensuring that ASCO provides up-to-date information about COVID-19 for patients, survivors, and caregivers through Cancer.Net. Since March 2020, she devoted a remarkable amount of time and energy to this endeavor, including a stretch of 650 straight days of reviewing and updating our patient information about coronavirus. Wow. That's true dedication, Merry Jennifer. So I would like to kick it off to you, Merry Jennifer. First of all, thank you so much for everything you've done during these past couple of years in keeping our Cancer.Net website up to date for patients during these incredibly challenging times. I'm looking forward to having a conversation with you about all of this.

Dr. Markham: Thank you so much. It's been an honor and a pleasure. And the Cancer.Net team has been just fantastic to work with.

Dr. Gralow: Great. Glad to hear it. So Merry Jennifer, when you suggested that ASCO provide some patient-focused content on COVID and cancer, did you think we'd still be talking about this 2 years later?

Dr. Markham: Oh, I had no idea what to expect. No. I think I, like many of us, thought that this would be a very time-limited event and maybe by the Christmas time of 2020, that we would be done. We were all, of course, disappointed to learn that that was not how a pandemic plays out, but I definitely had no idea what my one email to the group would lead to.

Dr. Gralow: What do you remember about March of 2020?

Dr. Markham: It was a really scary time and a very uncertain time. None of us really knew what was going to come. We were watching how the pandemic or just the viral infection was playing out at the time in other countries, but really, we're not sure what was going to happen to our patients. And I was coming off a stint, I believe - the timing is a bit of a blur - on the communications committee for ASCO. And communications is something that I am passionate about, cancer communication with patients and with other colleagues. And I recall being in clinic and answering questions from patients. And really, it felt like there needed to be some broader level of communication that our patients could refer to you but also colleagues and people around the world. That's what I remember. And I remember reaching out and saying, "Hey, I wonder if maybe ASCO should do something." I didn't intend to volunteer myself to do something, but somebody needed to jump in, and I was ready.

Dr. Gralow: Well, I was still practicing at the time, and I know all the different questions that we were getting. It was such a confusing time. We didn't have information. It was changing on a daily basis. I'm impressed that you thought that we were going to be dealing with this maybe even until the end of 2020 because I was thinking, "Oh, 3 or 4 weeks. We can all quarantine for 3 or 4 weeks. Right?" And here we are more than 2 years later. So you worked on the content for 650 days straight. I mean, every single day for 650 days, you looked to make sure that what we had on there was accurate, and now we backed off a little. But you're still looking at the content a couple of times a week. How has that level of focus on COVID-19 affected your perception and experience of the pandemic?

Dr. Markham In the very beginning, the content was really updated daily. I think something was changing on a daily basis. And so it became part of my morning habit, first thing in the morning with a cup of coffee if I had time for that, to read whatever was happening in the news that day and just paying attention to where we were headed, knowing that there would be changes. In the beginning, there was not enough masks, so we weren't recommending everyone "Go out and buy surgical masks." And then the policies changed on that as we had plenty of masks and then, of course, vaccines and so on and so forth.

I think I felt, like many people, a loss of control when the pandemic happened. Right? I think that so many people felt the sense of loss and the sense of uncertainty. And it reminded me actually of what patients with cancer probably experience with a new diagnosis, the sense of loss and uncertainty for what the future holds. And I think like many of my patients who really want to dive in deep to the research of their own cancer and treatment course, it actually gave me a sense of comfort to delve deep into the facts of what we were learning on a daily basis about COVID. Having that knowledge at my fingertips and being able to put it into layman's terms really did help me, I think, not become emotionally tied up in all of the sadness of the pandemic and the loss of travel and the loss of being able to be with loved ones. So for me, it was a little bit of a coping mechanism, I think. I didn't realize that at the time, but in hindsight, I really think it was.

Dr. Gralow: So becoming a true expert in COVID and cancer was your coping mechanism. That's interesting because you were the leading authority here on what everyone was recommending. Do you have any particular moments, good or bad, that really stand out for you from those early days?

Dr. Markham: I think what stands out the most is we focus so much on science as practitioners of oncology and in these health professions and as scientists. And I remember being very disappointed and hurt whenever I encountered someone, whether it was a patient or a family member or a colleague or-- not colleague but acquaintance, perhaps, who didn't believe that this was a real thing. And I was really pouring my heart and soul into the work of providing patient education on this and trying to do the same in my own clinic and with my own family members. And to have people brush it off as a non-thing, it was hurtful, and it was also just very disappointing as a physician and scientist.

Dr. Gralow: And things were changing fast. Now, you yourself ended up with a COVID diagnosis at the end of 2021. Did that personal experience change the way you viewed ASCO's roles in supporting people with cancer throughout the pandemic?

Dr. Markham: So I was minimally symptomatic, which was really thanks to science and thanks to the vaccines and having boosters. So number 1, it was very mild. But like many people who have a diagnosis that's new to them, I was nervous. And so I did feel reassured, though, because I had a pretty good understanding of what was happening and what was going to happen, and I knew that I was protected because of the vaccine and boosters. But it can be a scary time, and I think that it just gave me a little more insight into what people who I've taken care of, who have cancer and then have experienced a COVID diagnosis, have felt. Unlike my patients with cancer, I'm not immunocompromised, so I felt pretty comfortable. But it can certainly be scary. And I did have that appreciation for-- not just the infection but having to isolate myself from my family, I think that really was the hardest part and the inconvenience of it.

Dr. Gralow: Well, I'm glad you just had a mild case, and hopefully, you have no residual symptoms. But it is interesting when you have, either within your family or yourself, a personal confrontation, either with COVID or with cancer, that it gives you a different perspective.

Dr. Markham: Absolutely. That is so true.

Dr. Gralow: So we're now 2-plus years into the pandemic. I know you don't have a crystal ball, and I know we've thought we were on the downswing and things picked up again. But where do you see this going? I mean, not just COVID itself but public health, immunizations, the whole pandemic awareness. Where do you see this going in the U.S. and worldwide? We've had the flu coming around every season. We didn't wear masks. We have vaccines. Not everybody got vaccines. What are we going to learn from all of this, and where do you see the future will be?

Dr. Markham: I think that one of the major learning experiences that all of us who are in medicine and health care and those in health communication and health policy-- what we have learned is that science communication really does matter, and it's hard to do it in a very rapid-fire pace and do it well. But I think we've all seen examples of how communication around factual data and removing misinformation is actually critical. I would love to see this pandemic go away, but I think that what we've seen over the last couple of years with the new variants coming out, it's clear that we're not going to have 99% of our population vaccinated. I think, really, on all fronts, vaccination uptake is not that high. So there will be people who are either unable or unwilling or who will defer getting vaccinated. And unfortunately, this will lead to these waves of new variants coming like the current variant that is circulating. But I do think that there is hope.

One of the reasons that a lot of my patients delayed getting vaccines in the beginning-- many of mine did, but there were some holdouts who really were not comfortable getting vaccinated. There is now more time. And so we do have more safety data, and we know that the vaccinations are safe against-- the COVID vaccinations are safe. So I think that I have seen more patients in those last 6 months become vaccinated. They were holdouts initially, and now more are doing it. And I'm hopeful that this trend will continue. I do think there are pockets where we are seeing vaccination rates start to pick up again. I don't know. I'm happy to keep reviewing content, though, and updating. The updates have become a little less frequent, which is great. I love when our focus on updating is really on new therapies and new vaccines and new vaccine sequences and schedules. So I think we're in a fairly stable place - knock on wood - right now.

Dr. Gralow: In our immunocompromised population, which is only a subset of all of our patients with cancer, do you think we'll see more mask wearing in the future?

Dr. Markham: I do. I do think that actually this is one area where we, as a culture, have probably begun to shift in the United States and especially among people who have a personal risk or a family member with a risk factor that might increase their chances of severe COVID. Just a personal anecdote. I traveled internationally for the first time since COVID a couple of weeks ago, and my entire family, all vaccinated and boosted, wore our masks, as it's the federal requirement to do so on planes. However, we landed in an international location where that was not a requirement. None of us wanted to take our masks off. We felt more comfortable, and I saw a lot of people who also remained masked even though it was not a requirement. So I do think there's a shift in this culture. I'm as tired of the masks as anyone, but it really does have a protective measure and is, I think, important, especially for our patients who have a weakened immune system or other medical risk factors for developing COVID or other infectious diseases.

Dr. Gralow: So kind of in closing, you did such tremendous work for ASCO, for our patients with these regular updates. But what's the experience meant to you as an ASCO member and a member of the oncology community?

Dr. Markham: I joined ASCO when I was a fellow, and I was taught the importance of our organization by my faculty members and my mentors. And as soon as I realized I could, I volunteered to serve on ASCO committees and task forces. And it has been one of the most rewarding parts of my career. And it's something that I encourage junior faculty and fellows to do as well. ASCO is such a leading voice. It is the leading voice for oncology care globally. And just the opportunity to contribute something back has really meant the world to me. It's been an honor to be able to do this work.

Dr. Gralow: Well, on behalf of ASCO, I want to thank you again for all of your commitment to this. We're thrilled to have you as a volunteer, and we will continue to call on you as a volunteer. Really appreciate that. And I do know that throughout the COVID-19 pandemic, a lot of what ASCO was posting, a lot of the webinars we had, etc., were being used around the world. And you contributed majorly to that as well. So for that, I thank you. And I thank all of our listeners. This has been Julie Gralow and Merry Jennifer Markham talking about our Cancer.Net COVID-19 information that Merry Jennifer tirelessly led daily, essentially, for a couple of years. So thank you so much for that. It's been great talking to you.

Dr. Markham: Thank you.

ASCO: Thank you, Dr. Gralow and Dr. Markham. Find all of Cancer.Net's resources on COVID-19 and cancer at www.cancer.net/covid19.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.  

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. 

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate. 

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, 4 Cancer.Net Specialty Editors discuss new research in prostate, bladder, kidney, and testicular cancers presented at the 2022 Genitourinary Cancers Symposium and 2022 ASCO Annual Meeting.

This episode has been adapted from the recording of a live Cancer.Net webinar held June 15th, 2022, led by Dr. Neeraj Agarwal, Dr. Timothy Gilligan, Dr. Petros Grivas, and Dr. Tian Zhang.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig (TOSS-ig) Cancer Center.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center.

Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center.

Full disclosures for Dr. Agarwal, Dr. Gilligan, Dr. Grivas, and Dr. Zhang are available at Cancer.Net.

Greg Guthrie: Good afternoon, everyone. I'm Greg Guthrie, and I'm a member of the Cancer.Net content team. I'll be your host for today's Research Round Up webinar focusing on cancers of the genitourinary tract. Cancer.Net is the patient information website of the American Society of Clinical Oncology, known as ASCO. So today, we'll be addressing research from 2 2022 scientific meetings, the ASCO Annual Meeting held in Chicago in June and the Genitourinary Cancers Symposium held in San Francisco in February. Our participants today are all Specialty Editors of the Cancer.Net Editorial Board, and they are Dr. Neeraj Agarwal of the Huntsman Cancer Institute in University of Utah, Dr. Timothy Gilligan of the Cleveland Clinic Taussig Cancer Center, Dr. Petros Grivas of the Fred Hutchinson Cancer Research Center and University of Washington, and Dr. Tian Zhang of the University of Texas Southwestern Medical Center. Thank you, everyone, for joining us today. So starting us off today is Dr. Agarwal who will be talking about research in prostate cancer. Go ahead, Dr. Agarwal.

Dr. Agarwal: Hi. Thank you, Greg. So I'd like to start with 2 studies. They both are in prostate cancer which will be followed by my colleagues presenting studies in other cancers in bladder cancer and kidney cancer. So I'll start with this abstract, which was highly discussed by the doctors at the ASCO Annual Meeting a few weeks ago, and it has a lot of relevance in our practice. So this is abstract #5000 presented by Dr. Michael Hofman, and this was the update on a clinical trial which compared lutetium PSMA-617, or lutetium PSMA, to put it simply, with cabazitaxel in patients with metastatic castration-resistant prostate cancer who had disease progression after receiving docetaxel chemotherapy.

So, who were the patients who were enrolled on the study? These patients had, as I said, metastatic castration-resistant prostate cancer, who had disease progression after docetaxel chemotherapy, and who had to have high PSMA-expressing prostate cancer. And the way they assessed the presence of high PSMA expression was by using a specialized kind of PET scan known as Gallium 68 PSMA-11 PET scan. In addition, they made sure that these patients do not have another type of prostate cancer, also call it dedifferentiated prostate cancer, by making sure that those patients did not have a traditional PET scan-positive disease.

So this was a highly selected patient population who were expressing PSMA on their prostate cancer. Prior to this presentation, the earlier presentation had shown that lutetium PSMA was superior to cabazitaxel as far as progression-free survival is concerned and also was associated with lower incidence of grade 3 or 4 side effects. In this update, after a longer follow-up of 3 years, Dr. Hofman and Dr. Davis, who is a senior author, they presented the data on overall survival, which was a secondary analysis, and overall survival was similar with cabazitaxel as well as lutetium PSMA in the range of 19 months. We did not see any new safety signal.

So, what does it mean for us? What does this mean for our patients? My key takeaway message here is, lutetium PSMA is a suitable option for men with metastatic castrate-resistant prostate cancer who are expressing high PSMA on their prostate cancer after they had sustained disease progression after docetaxel. However, cabazitaxel is also a valid option in this setting. I would like to add my own view in addition to this because lutetium PSMA was better tolerated and was also associated with better progression-free survival. In my patients who are progressing on docetaxel chemotherapy, I would like to use lutetium PSMA first followed by cabazitaxel chemotherapy. So that would be my key takeaway from this abstract. Now we can move to the next abstract.

This was also an update, a much longer update, on ENZAMET trial. If you recall, ENZAMET trial was one of those trials which established that deeper androgen blockade, or deeper androgen signaling inhibitors such as enzalutamide, apalutamide, or abiraterone, these trials were conducted in 2015 onwards, and all these trials showed that upfront using deeper androgen signaling inhibitors at the time of metastatic hormone-sensitive prostate cancer onset improved survival. So ENZAMET trial used enzalutamide, and it showed in the first analysis, which was presented by Dr. Davis and Dr. Sweeney in the 2019 ASCO Meeting Plenary session, that adding enzalutamide to androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer significantly improved survival. In this longer follow-up of 68 months, so we are talking about almost 6 years of follow-up, now, these investigators from ENZAMET trial, as presented by Dr. Davis, showed that the combination of enzalutamide with androgen deprivation therapy or testosterone suppression therapy continues to significantly improve survival in patients with newly diagnosed hormone-sensitive prostate cancer or metastatic prostate cancer. One interesting part of this unique aspect of this trial was that patients were allowed to receive docetaxel chemotherapy concurrently to the protocol treatment. And in this trial, 45% patients actually receive docetaxel chemotherapy. So 503 patients exactly out of 1,000-plus patients. So if you look at the subgroup analysis of those patients who received docetaxel chemotherapy, enzalutamide does not seem to benefit those patients from the overall survival perspective.

So on the face of it, it looks like enzalutamide is not helping those patients who are receiving docetaxel concurrently. But there are some caveats with that kind of subgroup analysis. The first one is this is not a randomized assignment of docetaxel chemotherapy. Patients were determined to have docetaxel chemotherapy after discussion with their respective oncologist. This was not a prespecified analysis that so many patients with docetaxel will receive enzalutamide. Also, this was not a randomized assignment of docetaxel. And third, that I don't think this trial had enough power to look for that subgroup analysis.

So my take on this trial is that updated results from this trial, almost 6 years of follow-up now show that enzalutamide continues to improve overall survival with a 30% reduction in risk of death in patients with metastatic castration-sensitive or hormone-sensitive prostate cancer. Furthermore, the effect of enzalutamide, in my view, on overall survival is independent of the receipt of docetaxel. If you look at the whole trial population for which the trial was covered for, enzalutamide improved survival for all patients. And based on these results, I feel more confident in saying that upfront intensification of treatment with deeper androgen inhibition remains a standard of care for our patients with metastatic hormone-sensitive prostate cancer and should be offered to all eligible patients with this condition. With that, I would like to wrap up the prostate cancer abstracts. Thank you very much.

Greg Guthrie: And thank you, Dr. Agarwal. Next up, we will have Dr. Gilligan, who is going to be discussing testicular cancer.

Dr. Gilligan: Thank you very much. So I have 2 studies I want to talk about and then just give a headline of some interesting things that I think are kind of coming down the road. Both of these abstracts have to do with improvement over time in specific patient populations we used to worry about. I'm not saying we don't worry about them anymore, but things are looking better now than they had 1 or 2 decades ago. So the first topic addresses late relapses in testicular cancer. And historically, we have been concerned that these patients did worse and had worse outcomes. And late relapse could variously be described as after 2 years or after 5 years. In the current study, they defined late relapse as being after 2 years and very late relapse as being after 5 years. And what was special about the study was that it captured the entire population of patients with testis cancer in Norway and Sweden so that it wasn't based on a center of excellence that gets selective referrals. It was actually a population-based study. And the key conclusion of the study was one I found, once again, that late relapses are rare. So for stage I patients, 2% of patients will relapse after 2 years, 1% after 5 years, and 0.5%, so 5 out of 1,000 patients, after 10 years. So if you're 2 years out, the likelihood of a relapse is quite low.

And if you're 5 years out, it's half of that. In patients with metastatic disease, similarly, 3.6% relapse after 2 years, 1.6% after 5, and 0.8% after 10 years. And what was interesting to me was that if you looked at the more recent patients who were diagnosed after 1995 - I know that doesn't sound very recent, but they had even earlier patients also in the study - the very late relapse rate almost resolved and went away. It went from 2.2% all the way down to 0.8%. So I think with modern imaging, modern care patterns, we're seeing less of this than we used to. But overall, patients were doing better even if they do relapse late.

One thing that was interesting in the study to me also was for stage I disease, we typically recommend surveillance rather than active treatment. So active treatment with non-seminomas would be a retroperitoneal lymph node dissection or more surgery or chemotherapy. With seminoma, it would usually be chemotherapy or radiation, although surgery is being investigated there now. And they did find that in men who chose surveillance, which we still recommend, the late relapse rate was a little bit higher, but it was still affecting a small percent of patients. So the relapse rate beyond 2 years was 4% rather than 1%, but out of 4,000 patients, there were only 3 deaths from late relapse. So this isn't changing the recommendation for surveillance, but it is an alert that patients who are on surveillance for stage I disease have a slightly higher risk of late relapse and that may affect how we follow them and specifically how long we follow them. One of the things that was interesting in the study is in the United States, we often stop scans at 5 years, but in the SWENOTECA countries, they continue scans all the way out to 10 years. I don't know that U.S. guidelines are going to change, but it was a provocative finding.

The key thing, as I alluded to at the beginning, was that 61% of patients with late relapse were alive 10 years later, and while we would like that number to be higher, it used to be around 50% in older studies. So it's a significant improvement from where we were before. A particularly interesting thing to me was that patients relapsing 2 to 5 years out actually had the best prognosis. Patients who relapsed in years 1 to 2 had a worse prognosis and patients relapsing after 5 years had a worse prognosis, whereas the patients relapsing 2 to 5 years had a better prognosis. In the end, I think what this means for us is that patients are doing better. It's not going to really change our treatment patterns, but it's reassuring that we shouldn't be pessimistic about late relapses, and we still have a solid chance of curing them. So again, bottom line, most men with late relapse is cured and late relapse is less common now than it was earlier, particularly in non-seminomas.

Let's go to the next study. So this is a different group of patients who had a particularly ominous prognosis historically and still we have a lot of room for improvement. These are patients with non-seminomas that start in the mediastinum. So in the chest, under the breastbone, under the sternum typically. And patients are treated aggressively upfront, they are considered poor risk at the initial time of diagnosis, and they're treated aggressively at the time with 4 cycles of BEP or 4 cycles of VIP chemotherapy. And then they go for surgery to remove any residual disease. And the hope is they're cured at that point because historically, if there was a relapse after chemotherapy and surgery, it was almost impossible to cure them. Indiana University published their results using high-dose chemotherapy in this population, and they reported that 30% of men who were treated with high-dose chemotherapy had no evidence of cancer after 2 years, and 35% were still alive.

Obviously, we need longer follow-up, but most of the relapses you're going to see are going to be in the first 2 years. So while again, there is significant room for improvement here, this indicates that high-dose chemotherapy is a good option, and that has been a question. So this is reassuring in that regard. But it is a good option for men with relapsed mediastinal non-seminomas of the germ cell tumors. So there's hope there where in the past, this has felt a little bit helpless.

The thing I wanted to also highlight was that there are 3 things I think are going to be interesting to keep an eye on over the next year. One is the use of surgery for early-stage seminomas. There are a number of papers out about that. I still think this is an investigational approach, and so I didn't want to go into great detail about it, but it is looking like that RPLND, or retroperitoneal lymph node dissection, will likely or may be an option for stage I and stage II seminoma in the future. We are getting more evidence for that. It's not quite as promising as we had hoped until there's more data that's needed, but it's looking like that will become an option. So for men with early-stage seminoma, at least raising the question whether surgery is an alternative to chemotherapy or radiation, is an important discussion to have with your oncologist.

Secondly, MRI rather than CT scans for surveillance. So to keep an eye on men who have been treated or men who are just stage I and are being followed and typically come in routinely for CT scans, which expose people to ionizing radiation, which theoretically has a risk of causing cancer, there's more and more data that MRI is just as good as CT, and MRI does not use ionizing radiation. So there's probably going to be an expanding role for MRI as an alternative to CT scans.

And lastly, the use of microRNA rather than just depending on serum tumor markers. So right now, we use the blood tests alpha-fetoprotein, beta hCG, extensively to monitor for relapse, and there's more and more evidence for using what we call microRNAs instead. It may be more accurate in multiple different settings. So it'll be interesting to see how that evolves and that's what I wanted to cover today. Thank you very much.

Greg Guthrie: Thank you, Dr. Gilligan. And now we have Dr. Grivas, who's going to discuss some research in bladder cancer.

Dr. Grivas: Thank you so much, Greg, and thanks Cancer.Net for the great opportunity to discuss this for our patients. We're very excited about the data from the ASCO Annual Meeting, and I would encourage the audience to review as possible other presentations as well. I'm going to cover 3 highlights. I'm going to start with the QUILT-3.032 study. This trial reported the final results of a clinical trial that took place in different centers and involved patients with what we used to call "superficial bladder cancer." And the modern term is "non-muscle-invasive bladder cancer." Bladder cancer that does not involve the muscle layers, not that deep in the bladder wall. Non-muscle-invasive bladder cancer is usually treated by our colleagues in urology with installation inside the bladder with an older form of immunotherapy which is BCG. And that's the most common way we treat this disease. And proportion of patients may have tumors that may not respond to BCG that may come back or persist despite the installation of the BCG in the bladder.

And these patients usually have a standard of care of getting what we call radical cystectomy, meaning, removal of the bladder and the lymph nodes around the bladder, radical cystectomy and lymph node dissection. However, many patients may not have, I would say, the opportunity to get the surgery because the body may not be that strong to undergo that significant procedure. Very few patients may have that challenge because of other medical conditions or what we call poor performance status. Or some patients for quality-of-life reasons may try to keep their bladder as long as possible. And for some of those patients, that might be an option.

And we have been looking for those options in the last few years. Intravesical, inside the bladder, installations of chemotherapy have been used with some positive results in some other studies. So that's an opportunity. We call this intravesical, inside the bladder, installations of chemotherapy, and the other option is an FDA-approved agent given intravenously inside the vein called pembrolizumab, which is in the form of immunotherapy. Of course, research continues. And this study I'm showing here from Dr. Chamie and colleagues, looked at this combination of BCG plus this molecule called N-803. This is another form of immunotherapy, and this was tested in patients who have this BCG-unresponsive, as we called it, non-muscle-invasive bladder cancer. The results were very promising. I would say impressive that it was a high response rate if we focus our attention on patients who had the superficial form carcinoma in situ, about 70% had no evidence of cancer upon further evaluation of the bladder. And in many of those patients that this response lasted for more than 2 years. 96% of patients avoided to have worsening of the bladder cancer in 2 years for those who had a response, and about 9 out of 10 avoided cystectomy again from those patients who had received the response. So it was 70% of all the population.

And as you see, all patients, 100% were alive without dying from bladder cancer after 2 years, which again is a very promising finding. This combination, to conclude, this inside the bladder installations of BCG plus the N-803, looks very promising. For those patients with BCG-unresponsive non-muscle-invasive bladder cancer, that might be an option down the road, we have to see.

Now I'm going to shift my attention to patients with metastatic or spread urothelial cancer. I want to point out that I'm a co-author in this abstract and I participated in that survey I will show you the results from. This is a population of patients who have spread cancer from the urinary tract, either the bladder was the most common origin or other parts of the urinary tract, for example, what we call kidney, pelvis and ureter, or rarely the urethra. The urothelial cancer that starts from those areas, again more commonly bladder, if it spreads, if it goes outside the urinary tract system, usually those patients get chemotherapy, what we call with an agent called cisplatin if they can tolerate that chemotherapy drug or carboplatin if they cannot tolerate the cisplatin drug. And usually either of these, cisplatin or carboplatin, is combined with a drug called gemcitabine. That's the most common chemotherapy used as initial therapy for patients with spread metastatic urothelial cancer. In this abstract, Dr. Gupta and colleagues tried to survey 60 medical oncologists, including myself, who treat urothelial cancer that considered experts in this disease type, to see if there are any features that could deter us from using chemotherapy in those patients. In other words, are there any features that may make us think that chemotherapy may be too risky for our patients and we should not do it? We should give immunotherapy instead.

This is probably a small proportion of our patients, maybe 10 to 20% in our practice, may not be able tolerate that chemotherapy. And which are those features? Poor performance status, meaning the body is very tired and the patient is not moving too much, is confined in the chair or the bed most of the day, and rely on others on daily activities. This is what defines the performance status of ECOG 3. Peripheral neuropathy, meaning that there is numbness or tingling or weakness in the hands or the feet that impact the quality of life. And patients may have trouble buttoning buttons or tying laces, so impacting the quality of life. That's grade 2 neuropathy. Symptomatic severe heart failure, there is a grading system, like New York Heart Association Class III or IV that is significant, notable heart failure symptoms. And also, patients with kidney failure with what we call creatinine clearance below 30 cc per minute. That's a marker how we measure kidney function and the creatinine clearance more than 60 is usually close to normal. As the creatinine clearance drops and goes below 30, chemotherapy with these platinum agents may become a challenge by itself or if it's combined with the ECOG performance status of 2, which means more patients are not moving most of the day.

So those features again have to do with the functionality of the day-to-day life. The presence of significant neuropathy, heart failure, and poor kidney function may potentially make the oncologist recommend immunotherapy versus the standard of care, which is chemotherapy, in those patients. And I would say if someone gets chemotherapy, which is the majority of patients, usually they may get immunotherapy later. So pretty much I would say discuss with the medical oncologist what is the right treatment for you. Most patients get chemotherapy up front, followed by immunotherapy. Some others may need to get immunotherapy, and those criteria help us make that patient selection for the right treatment at the right time.

So I just alluded to you that most patients with spread or metastatic urothelial cancer, most of them receive chemotherapy. We discussed some criteria in the previous studies that we may use immunotherapy upfront instead of chemo, but for the vast majority of patients, chemotherapy is used upfront and that was based on the results of phase 3 clinical trial called JAVELIN Bladder 100. This was presented at the ASCO Annual Meeting in 2020 about 2 years ago, and it was published in a big journal. And that study showed that if you give chemotherapy upfront, those patients who can tolerate the chemotherapy, of course, who do not have the previously listed criteria, those patients benefit and live longer, so longer overall survival, meaning they live longer, and they have longer progression-free survival, meaning they live longer without worsening of the cancer if they get immunotherapy with, immunotherapy drug is given through the vein, called avelumab.

If that is given after the end of chemotherapy for patients who have a response or stable disease, meaning no progression on chemotherapy. So if you get a complete response, meaning that the CAT scans look normal after chemotherapy as at least we can tell visually. Partial response, meaning that the CAT scans look better, but still we can see some cancer spots. Stable disease, meaning that the scans look stable compared to the beginning before we start chemotherapy. If someone has worsening of the cancer in chemotherapy, then the concept of maintenance therapy doesn't apply. So it's only for patients with complete response, partial response, or stable disease, SD.

And the poster we had, and I can tell you - I was a co-author in the abstract and co-investigator in the trial, as a disclosure - was sort of the benefit of the patient with avelumab as maintenance therapy after chemotherapy was notable in patients with complete response, partial response, and stable disease. So in any of these 3 categories, avelumab immunotherapy should be offered as level 1 evidence and benefit patients in terms of overall survival and progression-free survival as long as there's no progression to the upfront initial chemotherapy of the patient with metastatic urothelial cancer received. Many other abstracts on these cancers were presented, and I would encourage you to look at them. Thank you so much for the opportunity today.

Greg Guthrie: And thank you, Dr. Grivas. Next, we have Dr. Zhang who will discuss some research in kidney cancer.

Dr. Zhang: Hi everyone, glad to be here today. I'll be discussing 2 highlights from ASCO 2022 in kidney cancer. The first one we wanted to highlight was a trial called EVEREST: everolimus for renal cancer ensuing surgical therapy, a phase 3 study. And in context, this study is a trial of evaluating everolimus, an mTOR inhibitor, in the post-surgical context. And we do have in the landscape 2 approved therapies, sunitinib and pembrolizumab. And as we have seen, some effective therapies in the refractory setting, many of these therapies are being tested in this postoperative space. So this particular study of EVEREST looked at patients with renal cell carcinoma who underwent resection for their primary nephrectomy and looking to evaluate postsurgical treatment. So everolimus has been approved as a treatment on its own in the refractory setting as well as in combination with lenvatinib. And so this question of whether everolimus alone could delay or prevent disease recurrence in the postoperative setting was tested in this EVEREST trial. The study ultimately enrolled more than 1,500 patients and assigned them to receiving either everolimus or placebo in the postoperative setting. Of these patients, 83% had clear cell kidney cancer and the remaining had non-clear cell kidney cancer. And the follow-up was quite long, over 5 years, and actually over 6 years, and the researchers looked at time until disease recurrence. And risk of recurrence was actually decreased by 15% in patients who were treated with everolimus compared to placebo.

But the prespecified cut-off for a statistical significance was not quite reached, and the researchers took a specific look at a group of very high-risk patients defined by larger tumors, invasion of the perinephric fat in renal veins or invasion of nearby organs or known positive disease. And those patients with very high-risk disease had more benefit from everolimus compared to placebo. Of note, 37% of patients who were treated with everolimus had to stop treatment due to their side effects, and the most common severe side effects included mouth ulcers, high triglyceride levels, and high blood sugars. So ultimately this particular study did not show sufficient benefit of everolimus given the toxicity and lack of statistical significance. And so this is a balance between potential benefit in delaying recurrence versus treatment toxicities that we must have in this adjuvant setting.

So what does this particular study mean for patients? Well, it was certainly a large phase 3 trial performed in the cooperative group setting and through the generosity of 1,500 patients and the principal investigators on the study, we learned this answer for a very important question of whether everolimus makes a difference in this postoperative setting. I think we're not using this in clinical context currently, but in this postoperative setting, we are always balancing this risk of toxicity with the potential for benefit and discussing the potential treatment options. I do not think this particular trial changes the standard of care in this adjuvant setting.

And then I think finally for today's prepared talks, this abstract on depth of response and association with clinical outcomes with CheckMate 9ER patients treated with cabozantinib and nivolumab. So this was a post-trial analysis of patients who had kidney cancer with disease spread and treated with cabozantinib and nivolumab compared with sunitinib in the CheckMate 9ER study. And the context, this was the phase 3 trial in which the benefit of cabozantinib and nivolumab was established in the first-line setting and gained the registration and approval of this combination in the first-line treatment of metastatic kidney cancer. This particular analysis, presented at ASCO this year, was a post-trial prespecified analysis evaluating this depth of partial responses and associating those with clinical outcomes of time until disease progression as well as time until death.

These depth of responses were defined as 80 to 100% for PR-1, 60 to 80% for PR-2, and then 30 to 60% as PR-3. And as we saw in this analysis, the deeper the responses on cabozantinib and nivolumab, the more correspondence with higher 12-month rates of disease-free progression compared with those same depths of responses from sunitinib. And there were similar 12-month overall survival rates for patients with similar depth of responses for either the cabozantinib and nivolumab combination compared with sunitinib. So I do think the degree of partial response in these settings is productive of time until progression and establishes further the efficacy and benefit of cabozantinib and nivolumab compared with sunitinib. And what does this trial mean for our patients? I think that early on, as we're looking for responses and radiographic changes for our patients on cabozantinib, nivolumab in the first-line setting, these deeper responses are associated with longer time until disease progression, and we can counsel patients, to discuss whether cabozantinib and nivolumab is working for them. This could be an early indicator for how patients will do overall on this combination. So with that I'd love to wrap up and turn it back over to you, Greg.

Greg Guthrie: Thanks so much Dr. Zhang. And now it's time to move on into our Q&A session.

This is for you, Dr. Agarwal. So the question is utility of triple therapy, ADT plus docetaxel plus ASI and metastatic hormone-sensitive prostate cancer given ENZAMET was inconsistent with PEACE-1 and ARASENS. Would you give ASI concurrent or sequential after chemotherapy for tolerability? I'm assuming ASI here is androgen suppression, correct?

Dr. Agarwal: Yes. Great question. There are 2 questions here. Number 1, if I would use triplet therapy given the negative subgroup analysis of the ENZAMET trial, and number 2, what is the role of triplet therapy in general? The answer to the first question is ENZAMET trial, subgroup analysis is very different from preplanned, prespecified, well-powered analysis from PEACE-1 and the ARASENS trial. So yes, we saw discrepant results, but my impression from ENZAMET trial is enzalutamide is an effective option for all patients regardless of the receipt of docetaxel chemotherapy because that was a subgroup analysis. So I don't think it really affects negatively the results of the ARASENS and the PEACE-1 trial. But a bigger question here is triplet therapy versus doublet therapy? Is triplet therapy for all or doublet therapy for all? Answer is no. Triplet therapy trials only showed that adding a novel hormonal therapy or deeper androgen blockade to the backbone of ADT plus docetaxel improves survival.

These trials did not answer the question, if adding docetaxel chemotherapy to ADT plus, for example, enzalutamide or darolutamide or apalutamide, will improve survival. We do not have that question answered by any of the trials and unlikely any other trial will answer that question. So my take ADT plus docetaxel is replaced by ADT plus docetaxel plus these deeper androgen blocker therapy. So wherever I was going to use docetaxel chemotherapy, so those are the patients with visceral metastases or in my practice, when I do comprehensive genomic profiling, I see those molecular aberrations which predict lack of response to deeper androgen blockade such as baseline AR variants. Or if I see 2 out of 3 mutations of p53, RB loss, p10 loss, if I see 2 out of these 3, I tend to think about docetaxel chemotherapy. So in those patients where I'm using ADT plus docetaxel, I would add another androgen receptor blocker such as abiraterone and darolutamide. But when I'm using enzalutamide or apalutamide which I use for majority of those patients, my patients with metastatic hormone-sensitive prostate cancer, I do not think about triplet therapy.

Greg Guthrie: Thanks, Dr. Agarwal. We actually have a follow-up question, and this is, what is the role of oncology in low-stage early prostate cancer? Can neoadjuvant chemotherapy reduce the number of people who end up with metastatic prostate cancer?

Dr. Agarwal: This answer is very simple. There is no role of neoadjuvant chemotherapy in high-risk localized prostate cancer or any localized prostate cancer setting.

Greg Guthrie: Great. Thank you. Next question. I believe that this is for everybody. How long will it be until the information from the trials discussed will be used in the community clinics? What can patients do to bring this information to their less experienced doctors?

Dr. Grivas: So, Greg, just to clarify the question, is it about the translation of the results of the clinic from ASCO to clinical practice, generically speaking, or any particular tumor type or any particular data results?

Greg Guthrie: The way I read this question, it's more just kind of a broader scope question about just like, how long does the results of clinical trials make it to community practice, and what role can patients have in perhaps fostering this transmission of information?

Dr. Grivas: Of course, I can start briefly, and then my colleagues can add. I would say the world we live in right now, the information travels very quickly. It's much faster compared to the past. And I think there is much more alignment, in my opinion, in terms of information access between academic oncologists and community oncologists. If, for example, a trial result comes at ASCO being presented, and then there's a follow-up approval authority from a regulatory agency, this agent may be accessible to both community and academic practices. Of course, there are always opportunities for education, and Dr. Agarwal is the director of the ASCO Daily News, and he knows that well to disseminate the information well, broadly, in an equitable manner across academic oncologist providers and community providers. And I think CME, continued medical education practices, can help in that regard. And obviously, the other aspect of that is the ongoing clinical trials and how we can do a better job disseminating the opportunity for equitable participation in clinical trials across racial groups, ethnicity groups, minority groups, to give them the chance to participate in ongoing clinical trials that may change the practice down the road, which are just early thoughts. But other colleagues can comment.

Dr. Zhang: Yeah, if I could chime in. I think these continuing medical education programs, particularly in the context after large symposia like the ASCO Annual Meeting we just had, are particularly important. And the Best of ASCO series, as well as ASCO Direct Highlight series - I believe Dr. Grivas and I are hosting 2 of these - are very helpful, I think, to bring the latest findings from the ASCO Annual Meeting to our community colleagues. And they really are our colleagues. We work together with our oncologists within the community to take care of our patients, oftentimes for standard of care treatments. Patients can access them more in their backyards.

And I think from a patient standpoint on the second part of the question, they're able to hear these from patient-friendly platforms and to bring that to the attention of their oncologist, wherever that may be. It all helps in the grand context of clinical care. So I hope that these trial results and the latest findings from ASCO can get inseminated very quickly.

Dr. Grivas: And to also add very briefly, the role of patient advocacy groups, and in the bladder cancer work, there are many, for example, the Bladder Cancer Advocacy Network, World Bladder Cancer Coalition, and many others can help also in that regard and teaming up with all of us to disseminate information and also clinical trial access.

Greg Guthrie: Great. Thank you, everyone. We have a question for Dr. Grivas. After the survey results in the study you described, is there any plan to make a guideline or tool to make sure we standardize the definition of cisplatin/platinum ineligibility?

Dr. Grivas: Great question. Just 1 more thing on my prior answer, kudos to Cancer.Net for serving that mission, Greg and Claire in that-- or the previous question to have a complete answer. Answering this new question here, which is very important. I think the next step is to try to publish the results of the survey. The survey like the previous one done by Dr. Galski about 10 years ago-- it's a survey on expert oncologists, and it's a consensus-based definition. It's criteria that we came up with together. And I think the next step here is to publish this in a peer-review process. And our hope is by publishing these results, we can have a more formal definition to help guide our practices in academia, but also in the community oncology practices and make sure that we have a standardized way that we approach this therapy selection and of course, to help design clinical trials that for this particular patient population in order to improve outcomes in this setting. So hopefully publication will come soon.

Greg Guthrie: Thanks, Dr. Grivas. I'll just drop a really quick pitch there. Here at Cancer.Net, we do have a very broad array of information on clinical trials. And patients can come visit us at Cancer.Net and learn about clinical trials, what they mean, and how they help advance cancer research. We now have a question for Dr. Zhang. Based on the results of EVEREST and other trials approved systemic therapies in the adjuvant setting like sunitinib and pembrolizumab, are there ongoing other trials in this setting and is risk stratification used?

Dr. Zhang: The short answer is yes. There are ongoing adjuvant trials that build on pembrolizumab in the adjuvant setting. There's one that is looking at the addition of belzutifan with pembrolizumab in the adjuvant setting. So that trial is a global trial which is about to get started, if not enrolling already. And in the context of adding on in the adjuvant setting, I do think we really need to discuss with our patients how much of a benefit the treatment will have versus the real toxicity in the postoperative setting, many patients will not have symptoms from their cancer, so they may have some pain or healing side effects from surgery, but they won't have symptoms from cancer. So any toxicities from medications can be further amplified, so are we truly giving a lot of benefit in that context or not. So that's an individualized decision, and I do think conversations must be had to make that decision together.

Greg Guthrie: Thanks, Dr. Zhang. I want to ask a question myself of Dr. Gilligan. You had mentioned that microRNA is an emerging field of study, and I've heard about this in other types of cancer as well. I wonder if you could discuss that a little bit more.

Dr. Gilligan: Yeah, microRNA, the promise that holds is being a more accurate detector, specifically of testicular cancer. So the problem we have with alpha fetoprotein and beta HCG is half of the testicular cancers may not make 1 or both of those markers. So people can relapse without the markers going up, even though markers are most commonly what we see, there are a couple of different scenarios. Someone has stage I testicular cancer, which means their testicles removed and all their scans show no evidence of cancer. We know that 25% or so of non-seminomas and 20% or so of seminomas will relapse, even though we can't see what the cancer is, and the markers are negative in that situation. MicroRNA may be able to detect those people who still have cancer much, much earlier. So we know that they're, in fact, not stage I and that they need active treatment right away. So that's one place. Another place that we're seeing evidence is that men who've had metastatic testicular cancer. They go through chemotherapy, and they have residual masses. And we're wondering if there's cancer in those masses or is it all dead scar tissue or is it teratoma? MicroRNAs may be able to allow us to determine who needs additional treatment, who needs surgery without having it. Right now, we typically go in and operate just to figure that out.

So there are a number of situations in which we could more accurately stage patients and figure out who's cured and who's not cured much earlier in the course of disease. And for a patient, this would be fantastic, because right now, if you've got stage I disease with non-seminomas and you go on surveillance and somebody says you have a 25% risk the cancer is going to come back, that's a 1 in 4 chance that at some point in the next 2 years, most likely, or longer, you're going to have to suddenly drop everything and go through months of chemotherapy. If we knew on day 1, it looks like you're cured, but in fact, there's cancer hiding there somewhere, and we need to treat you now, that would be helpful to know so they can get it over with. And the other men, we could say we're really extremely confident that there's not a 25% risk, it's a 5% risk or something much lower. So there are a number of ways, if this really gets proven and there's emerging data that's promising, I think we could reassure men, treat them more appropriately, spare them unnecessary treatment, and give them more peace of mind.

Greg Guthrie: Great. Thanks, Dr. Gilligan. I think we have a question from Dr. Grivas now.

Dr. Grivas: Thank you, Greg. This is a great panel. I like to learn from my colleagues here. One question for Dr. Zhang, you have done so much work in the field, leading the field there, Dr. Zhang. Any comments about the ideal end points in the adjuvant setting in kidney cancer, urothelial cancer, disease-free survival or overall survival? Would you comment about how we design trials, and what will be an acceptable benchmark? And what is meaningful for patients, too, in the adjuvant treatment after radical surgery for kidney cancer and urothelial cancer?

Dr. Zhang: Oh, that's a great question, Petros. Thank you so much for asking. We have discussed this many times together because you and bladder cancer and myself and kidney cancer, we're thinking a lot along the same lines right as new immunotherapies get approved in the postoperative setting, so disease-free survival as an endpoint and recurrence-free survival as an endpoint is a valid endpoint. It's a direct result of the randomized treatment on the trial, so I do think that is the valid endpoint, and it's an endpoint that the FDA has approved the sunitinib and pembrolizumab indications in kidney cancer, nivolumab and bladder cancer. So I think it's certainly a valid endpoint to delay disease recurrence. How much of that is meaningful degree of improvement for an individual patient? Their own measure of recurrence is either yes or no. It's much more binary than population effects. So how much does that translate into benefits for the patient? I think that warrants deeper individualized discussion. But these disease-free survival endpoints in all of these studies is a valid endpoint to see whether the treatment is worthy in delaying disease recurrence in each of these disease types.

Greg Guthrie: Thanks, Dr. Zhang. We have one last question here, and I believe this is a follow-up for Dr. Gilligan. And what is the time frame for the rollout of microRNA 371 to the community?

Dr. Gilligan: I don't know the answer to that. I'm not sure that we have enough data right now that it's going to get approved. I think we're headed in the right direction, but it's very hard to know what the timing of that is. There are trials going on, so I don't know at the moment of exactly what the scenarios are in which people are going to be, which patient populations are going to be eligible, but there are trials going on. I think I'm hoping within the next 2 years or so, but I really don't know what the time frame is, unfortunately.

Dr. Grivas: And if I may add a more generic comment to Dr. Gilligan's wonderful answer is that when we have what we call biomarkers that are like metrics that can give us information about how the patient does over time, it's important to tease out what we call prognostic, meaning how can this biomarker give us a sense of the chance of recurrence, as Dr. Gilligan said, or death from the cancer. But also, the bigger question is, is it going to give us information to predict benefit from an individual therapy? And that's a bigger question in oncology that is a harder one. This predictive question and try to identify biomarkers and validate them to make sure they have, they're clinically useful. They can help us make treatment decisions in the clinic. And I'm very excited about what Dr. Gilligan discussed about the promise in the future. But more trials are needed for many biomarkers.

Dr. Gilligan: I think when we do this update next year, we'll have significantly more data then, I'm hopeful.

Greg Guthrie: Thank you to you all. Thank you, Dr. Agarwal. Thank you, Dr. Grivas. Thank you, Dr. Gilligan. Thank you, Dr. Zhang, for sharing this great research with us, as well as your expertise. It's been a real pleasure this afternoon. And to all of our viewers, thank you for joining us. You can find more coverage of the research from ASCO Annual Meeting and other scientific meetings at the Cancer.Net blog, which is at www.cancer.net/blog.

And if you're interested in more Cancer.Net content, please sign up for a monthly Inside Cancer.Net newsletter or follow us on social media. We're on Facebook, Twitter, and YouTube where our handle is always @CancerDotNet, with dot spelled out. Thank you all, and be well. Thanks.

ASCO: Thank you, Dr. Agarwal, Dr. Gilligan, Dr. Grivas, and Dr. Zhang. You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, members of the Cancer.Net Editorial Board discuss new research in molecular testing, also known as biomarker testing or tumor marker testing, to help guide treatment for people with early-stage non-small cell lung cancer. This podcast is led by Dr. Ryan Gentzler, Dr. Xiuning Le, Dr. Brendan Stiles, and Dr. Vamsidhar Velcheti.

Dr. Gentzler is the director of the Thoracic Oncology Clinical Research Program at the University of Virginia (UVA) and chairs the UVA Cancer Center's Lung Cancer Translational Research Team. 

Dr. Le is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Internal Medicine at The University of Texas MD Anderson Cancer Center.

Dr. Stiles is chief of thoracic surgery and surgical oncology at Montefiore and Albert Einstein College of Medicine.

Dr. Velcheti is the director of thoracic medical oncology at New York University Langone's Perlmutter Cancer Center.

View disclosures for Dr. Gentzler, Dr. Le, Dr. Stiles, and Dr. Velcheti on Cancer.Net.

Dr. Gentzler: Thank you, everyone, for joining us. We've got a great group here today, and we're really going to focus on talking about molecular testing in lung cancer. This is a very hot topic. My name is Ryan Gentzler from the University of Virginia. I'm a thoracic medical oncologist. We have Drs. Le, Stiles, and Velcheti with us today. I'd like them to go ahead and introduce themselves, starting with Dr. Le.

Dr. Le: My name is Xiuning Le. I'm an assistant professor. I'm at the MD Anderson Cancer Center here in Houston, Texas. I'm also a medical oncologist. Thank you, Ryan, for inviting us today.

Dr. Stiles: Hey, everybody. I'm Brendan Stiles. I'm a thoracic surgeon. I'm chief of thoracic surgery at Albert Einstein College of Medicine in Montefiore Health System here in the Bronx in New York.

Dr. Gentzler: All right, thanks for joining us. And Dr. Velcheti.

Dr. Velcheti: Thank you, Ryan. I'm Vamsidhar Velcheti. I'm the director of the thoracic oncology program at NYU.

Dr. Gentzler: All right, great. We hear a lot of terms thrown around about molecular testing, genomic testing, biomarkers, oncogenic drivers, and I thought it would be good to just define what exactly is molecular testing, so all of our listeners are aware of what we're talking about. Dr. Le, do you want to take this question?

Dr. Le: Yeah. So we have many terms, as you described. In my eyes, there are 2 sets of testing, and then some of them also classify into actionable versus not actionable. So for clinical use, we usually ask the tumor to be tested for both the mutations as well as the immune marker. Usually, the panel of mutational testing is more than a field. Usually, it's depending on the platform we're using, oftentimes in the hundreds of things. And then the immune markers, usually, we refer to PD-L1 and the tumor mutational burden. Those are the 2 commonly used markers now in the clinic. Some of those markers, especially the hundreds in gene testing, not all of them can lead to a clinical decision because we're still in the phase of understanding the interactions of different genes. However, there is a subgroup of those mutations. Nowadays, we have targeted therapy for, we call those actionable mutations. So in the clinic, we push for testing for a panel of mutations as well as immune markers, hoping to look at the tumor comprehensively so that we can recommend a good treatment regimen precise to that particular tumor, precise to that particular patient.

Dr. Gentzler: Yeah. Wonderful. This has also been termed precision medicine, where we really match a therapy to a specific genomic abnormality identified on these tests and maybe, Dr. Velcheti, if you could maybe elaborate on some of the different ways that these tests are performed and how we're using these in clinic today?

Dr. Velcheti: Yeah, definitely. I think our understanding of the biology of lung cancer has evolved quite dramatically over the past several years and obviously it's led to a lot of advancements in terms of treatment opportunities for patients. Broadly, the way I look at biomarkers in lung cancer or, for that matter, any cancer, it's like you have biomarkers that actually kind of give us very deep insights into the biology of the cancer and giving us insights into how aggressive somebody's cancer is. Those are called prognostic biomarkers, kind of predicting outcome. And there are predictive biomarkers where there are certain biomarkers. If you do have some of these biomarkers in the tumor, then you could potentially use certain treatments that might work better for patients who have those biomarkers. So now we have a lot of different approaches in terms of how we kind of test for these biomarkers. Especially in lung cancer, now we have a lot of new therapeutics for certain genomically categorized types of lung cancer.

And the challenge now is that we have so many different mutations we absolutely need that information to decide on treatment. So how do we test that? Until a few years ago, we've been doing a single gene testing. The problem with those approaches is that we have so many different genes we need to test and we kind of do sequential gene testing, a single gene testing, we won't get all the information we need to make the right decision for our patients. So the standard approach in most oncology practices, especially larger cancer centers and academic medical centers, is do comprehensive genomic profiling, and that's being widely accepted as a standard approach right now.

Dr. Gentzler: Wonderful. And this has really been something that has fallen on the laps of thoracic medical oncologists as we've treated patients with advanced stage or stage 4 disease. And this is starting to become more and more important and relevant for surgeons. And Dr. Stiles, I just wanted to bring you into the conversation and see if this is something that, prior to some of the more recent data, which we'll discuss in a minute, is this something that as a surgeon, you've kept up with and think it's important in a surgical practice?

Dr. Stiles: Yeah, definitely, Ryan. And I think now is probably the most exciting time for that, right? We used to just be sort of in the prognostic side, like Vamsi said, but now we really are in the predictive side in the early-stage disease. And I think that's why everybody is so excited. But that's why there's now this pressure about the timing of biomarker testing. What do you get? Do you get a whole panel? As we'll talk about some of the trials that have made their way into earlier stage disease, but it becomes inherent upon surgeons to really think about this and understand this, from the first time that they meet the patient I think, as we increasingly get better therapies in earlier stage disease.

Dr. Gentzler: So as this has moved into earlier stage disease, a lot of this has been driven by some new data from clinical trials, and Dr. Velcheti, I thought maybe you could comment on the IMpower010 trial and its relevance and why molecular testing is important in the context of that trial.

Dr. Velcheti: Yes, absolutely. I think the IMpower010 Trial is certainly a new shift in our approach to treating stage I, II curable non-small cell lung cancers. So we haven't had an approval in the adjuvant setting in a while. I mean, of course, we had approval with the osimertinib result of the ADAURA trial, but that's only for EGFR patients. Now we have approval for using immunotherapy in the postoperative adjuvant setting for patients with any level of PD-L1 expression. So this is a large randomized study looking at the role of adjuvant atezolizumab, which is a PD-L1 inhibitor in patients who have PD-L1 expression greater than 1%. Patients were randomized getting platinum doublet alone, which is a standard-of-care adjuvant assistant therapy for patients at stage I, II lung cancer. It is atezolizumab at a dose of 1,200 milligrams given every 3 weeks. Patients who received atezolizumab had significantly improved outcomes in disease-free survival. And the benefit was actually really striking for patients who had high PD-L1, patients with PD-L1 testing TPS score of greater than 50%. They had a really remarkable increase in terms of disease-free survival for those patients. So this is certainly very encouraging. And of course, we know it's now approved. We are still awaiting some overall survival results to mature. But given the extent of the benefits we're seeing with the disease-free survival, I think it's a very promising approach.

Dr. Gentzler: Yeah, so obviously, immune therapy has had a tremendous benefit in the adjuvant setting from this trial and still some longer-term follow-up that's needed. But I think the important point here is that molecular testing may identify certain mutations that may make patients less likely to benefit or respond, or perhaps there's more appropriate treatments than immunotherapy within this group. And that brings us to the next trial that I think really shifted this discussion stage with the ADAURA trial. Maybe Dr. Le, if you could summarize this trial and give us your thoughts on why molecular testing is so important in the era of ADAURA.

Dr. Le: Yeah. So ADAURA trial is also an adjuvant trial, meaning that the patient received additional treatment after the completion of surgery. So ADAURA trial looked at patients who have EGFR mutations. So it's a different biomarker. It's a gene biomarker, not the immune biomarker. So this is a large international trial, enrolled almost 700 patients and then randomized the patients after surgery, after standard chemo, the patient can go on to either receive 3 years of osimertinib, which is the standard-of-care therapy for EGFR mutant patients for metastatic setting, or the control group if the patient just received standard of care, which is to continue the monitoring. The trial actually showed that for people who had osimertinib before that prolonged time of 3 years, the risk of the disease coming back is almost 5 times lower than the patient who did not receive therapy. So based on that really striking benefit of after surgery, after chemotherapy, continue osimertinib in EGFR patients, FDA approved after the surgical resection and all the standard care patient can go on for osimertinib for a prolonged time, which we think currently the data is saying the disease is more likely not to come back. And hopefully, in the future, that result will translate into overall survival benefit.

Dr. Gentzler: Okay, wonderful. And I think both of these trials, both the ADAURA and the IMpower010, are adjuvant trials. So these are trials that allow us adequate time to do molecular testing on a large surgical specimen, formulate our plans, and implement those plans up to a month or longer after surgery. Obviously, there's some new data that we've seen in a press release from the CheckMate 816 trial. This is a neoadjuvant trial of chemotherapy plus nivolumab. We've seen previous data from this trial showing some results, but this moves the conversation into the neoadjuvant space, and Dr. Stiles, I wonder if you could give us a summary of your thoughts on the CheckMate 816 and the relevance for molecular testing in that context of neoadjuvant therapy.

Dr. Stiles: Yeah. Thanks, Ryan. I think, first of all, those are incredibly important adjuvant trials. I saw 2 patients each this week on adjuvant osimertinib and adjuvant atezo [atezolizumab], so it's real-life practice. Every day, it's going to benefit patients. But I think that's easy, like you said, these are big specimens that are taken out. You've got time to decide while the patient gets better. Now, we have to shift all this even earlier because CheckMate 816 really has some pretty impressive results. We, unfortunately, don't have the paper yet. I'm told it's going to be coming out soon, but the primary endpoint pathologic complete response 24% versus 2.2%. That's with chemo-nivo versus chemo alone. Obviously, people are questioning, does pathologic complete response correlate with outcomes? Certainly, we got a signal on a press release that the event-free survival is going to be the hazard ratio is 0.63, so it sounds like it does, and I think we'll see more data on that in the next couple of months. A difference in median event-free survival of 32 months versus 21 months in the report. So everybody is excited to see this. And I think it has some advantages over the adjuvant strategy. First of all, more patients are able to tolerate it. It's just 3 cycles, and so it's not given indeterminately for a year.

And it worked across different subgroups. And we can talk about some of the nuances, but as where atezo [atezolizumab] was only looking good in the PD-L1-high. This sort of worked across different groups. The caveat to that is we don't really know what happens with these EGFR patients who are eligible and sort of, how do we then move that test? And all of a sudden, we've got to make a decision on neoadjuvant therapy. Now we need to know. It helps to know the PD-L1 maybe preoperatively, with the high PD-L1, maybe you could wait until adjuvant therapy, with the low to sort of medium PD-L1, maybe you want to give them their shot in the neoadjuvant space. But if they have an EGFR mutation, it's probably not the right thing. We don't really know the data on that and CheckMate 816 yet, but certainly, I'd be sort of hesitant to give them neoadjuvant chemoimmunotherapy. So then you have to teach surgeons all this too, and teach them to think about this and teach them to hold their horses on taking patients to the operating room while they wait for molecular testing. But that probably means we need to speed up the process somewhat either with sort of more rapid turnaround test, with consideration of liquid tests in some instances. It's just an incredibly fast-changing place that here we are speaking about a trial that hasn't even been published yet, so that tells you how fast things are happening.

Dr. Gentzler: One last question. How can the results of these tests guide therapy after surgery? Do we incorporate a full NGS [next-generation sequencing] panel at the time of surgery? And we don't have data on adjuvant therapy for ALK or ROS1, or RET. Do we factor that into how we think about adjuvant chemotherapy, adjuvant immunotherapy, do we employ targeted therapies for some of these mutations? Any thoughts on that?

Dr. Le: Ryan, I think you bring an important point in that EGFR is 1 of the 8 actionable mutations we have nowadays based on FDA and NCCN. The tumor biology between EGFR and ALK-fusion oncogenesis and potential response and benefits probably share some similarities. So we look forward to seeing trials reporting out the adjuvant setting with ALK inhibitors with ROS1. And the smaller target might require a multi-institutional or co-op group effort to really achieve the sample size for us to see. But as of now, we don't have the approval. We try to enroll patients to the oncogene trials, but I think currently we're practicing based on EGFR and PD-L1.

Dr. Stiles: Yes, and I agree. I'm excited to see what comes out of some of those trials. They're slow to grow, but we'll eventually get some readouts. I think an interesting question sometimes is PD-L1. And we had an example recently where in the pre-op biopsy, the patient had a low PD-L1, and so not particularly enthusiastic. And the question sometimes arises, do you test that whole tumor to consider them as kind of an adjuvant to atezo [atezolizumab]and then the fully resected tumor, the PD-L1 was greater than 50%. And so I would sort of sound a caution that the small biopsy sample, they're incredibly helpful for many things, incredibly helpful for moleculars. It may not always be totally representative of the PD-L1 staining.

Dr. Gentzler: And I think that's a good point. Even for molecular testing, sometimes if you have smaller biopsies, you may get a result that's negative, but it could be low levels of DNA and not sufficient to complete the full panel with high quality. So you really have to pay attention to the report and make sure that there's some confidence in the amount of DNA in some of these results.

Well, I think that's all the time we have here, so I appreciate everyone's participation, and hopefully we're able to learn a little bit about genomic testing today.

ASCO: Thank you, Dr. Gentzler, Dr. Le, Dr. Stiles, and Dr. Velcheti. Learn more about treating lung cancer at www.cancer.net/lung. 

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today, we're going to be talking about clinical practice guidelines, including what they are, how they're developed, and how they can impact care for people with cancer. Our guests today are Dr. Jeffrey Meyerhardt and Dr. Scott Tagawa. Dr. Meyerhardt is the Douglas Gray Woodruff Chair in Colorectal Cancer Research, clinical director, and senior physician at the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute. He is also the Cancer.Net Associate Editor for Gastrointestinal Cancers. Thanks for joining us today, Dr. Meyerhardt.

Dr. Meyerhardt: Thanks Brielle.

Brielle Gregory Collins: Dr. Tagawa is a professor of medicine and urology and the medical director of the Genitourinary Cancer Research Program at Weill Cornell Medicine. He is also the chair of ASCO's Evidence Based Medicine Committee, which works to create clinical practice guidelines. Thanks for joining us today, Dr. Tagawa.

Dr. Tagawa: Thanks for the invitation.

Brielle Gregory Collins: Before we begin, we should mention that Dr. Meyerhardt and Dr. Tagawa do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to start, Dr. Tagawa, what are clinical practice guidelines?

Dr. Tagawa: So as the name implies, there's clinical practice. So I as a practicing physician, for instance, might have a patient in front of me, and sometimes I want to know, what's the best thing to do? What is the best test that I might want to get? What is the best type of a treatment to use? I think these are especially important as the numbers of different types of cancers continues to grow, as we have more diagnostic tests and number of treatments that we have continues to grow. It's very hard for an average clinician to remember everything that's there. So we have guidelines that will give us information and general guidance for a particular situation, for a general patient population. Those don't necessarily mean that for an individual patient, that's something we have to do. But again, for the average patient in this individual situation, it helps us guide the physician or practice team in what we should do.

Brielle Gregory Collins: Got it. Thank you so much for explaining that. And, Dr. Meyerhardt, how can guidelines impact care for people with cancer?

Dr. Meyerhardt: Yes. So there's a lot of data that's out there for a lot of different cancers. And so to keep track of that, all of the different pieces of a study, it is helpful for groups of experts to get together and say what's really the right care for patients with this condition and what are the different options for them. And it really helps to really collate those all together and to be able to help clinicians decide what's the right initial step and subsequent steps for the care of a patient. As Dr. Tagawa said, it may not be the exact thing that's right for every patient. And the guidelines really do help with some of those caveats, like if the patient has certain liver function or if the patient has a certain molecular marker or something about their tumor that makes their cancer a little different, what would be the way to treat that as well? So guidelines really do help clinicians guide what's the right care for a patient at different steps along their cancer course.

Brielle Gregory Collins: Okay, thank you. And Dr. Tagawa, I want to talk a little bit about how guidelines are created. So can you describe the overall guideline development process?

Dr. Tagawa: Sure, there's a number of steps. So 1 step is identifying which guidelines are needed. So when there is a need. For instance, when there is more than 1 type of a treatment available and some data, then we generally consider that 1 of the most important types of topics to cover. When there 100% agreement with everyone in the world that 1 thing should always happen, that's less important for guidelines. And when there's zero data, that's also less important for guidelines. Although there are different types of guidelines. There's evidence-based, and you've mentioned the name of the committee that I'm on right now, Evidence-Based Medicine. But there can be consensus. So getting a group of different stakeholders, meaning physicians, nurses, etc., plus patients, together to come up with a consensus or expert opinion. So those do happen. But anyway, we identify a need, then we generally-- at least this is the way that we work it with ASCO, we get a panel together. At the very beginning of your statement, you mentioned conflicts. So we'll put together a panel of people with some sort of expertise, like maybe some scientific expertise or experience in treating, but also those that don't have at least too many conflicts on a research basis or financially, we will do a wide search to gather the best level of evidence, collect the evidence, and analyze the evidence into different levels.

Some types of clinical trials, for instance, are more important than others. We will synthesize that, put it all together, and then we'll come up with guidelines. Actually, 1 thing I forgot to mention in the beginning is we'll come up with specific questions. So for lung cancer of a certain type that's never been treated, what are the top questions? So that will guide the search. And then coming back, once we have all that evidence collected and synthesized and put in order, we'll then answer those questions. So 1 type of lung cancer that has a specific type of tumor genetic mutation in that setting, then we'd say treatment A is the best option, with B and C as options, for example. And that will be synthesized into a guideline and then put out to the public. Actually, there is a review process-- sorry, a public review process that anyone, at least ASCO does, that anyone in the world can have input on. And then, when we talk about peer-reviewed literature for a journal, for instance, we send it out to independent people. There are people that will review this, comment upon, that will come in, and we will revise things. And then the different guidelines hopefully are going to be approved and then published in journal formats, in internet formats, podcast format, etc., to hopefully get the message out.

Brielle Gregory Collins: Okay, thank you. I want to clarify the recommendations that are within guidelines. So basically, these panelists get together and they review the necessary evidence to make the recommendations. Is that correct?

Dr. Tagawa: Correct. And there are different levels of evidence and different levels or strengths of recommendations. So when there's a lot of high-quality evidence, and it all points in the same direction, that is going to be a very strong recommendation with a high level of evidence. And then there's intermediate, and then there's less evidence or extrapolated evidence, in which case, there still might be a recommendation because some of the time, let's say, for instance, in a rare tumor type or a common  tumor type that has a manifestation, say the cancer that spread to the brain, called brain metastasis, that hasn't been studied before, but we want to know what to do if we get into that situation. So sometimes there are statements that will say in this situation with the best available evidence, our panel recommends this.

Brielle Gregory Collins: Okay. That makes sense. And Dr. Meyerhardt, I want to talk a little bit about the role of clinical trials in guideline development. So can you talk a little bit about that role that clinical trials play in the development process?

Dr. Meyerhardt: Yeah, I think particularly for treatment for patients, a clinical trial is really critical. So a clinical trial is basically asking a question about a treatment. Sometimes it may be that everyone gets the exact same treatment. Sometimes it's just trying to find initially a dose of a treatment. And then ultimately trials often will be randomized to either something that's standard treatment or comparing 2 different treatments to see which has more efficacy and safety and considering quality of life and other factors that are important in the treatment of patients. And as Dr. Tagawa said, the level of evidence is important in considering guidelines. And so when a guideline is being created, we do look at trials that are particularly randomized trials, trials that have larger populations, trials that may have a more diverse population, so we can understand how certain treatments may be different based on various demographic factors of the participants in that trial.

And they really are critical because you could do a trial of 10 or 20 patients, which occasionally is enough to enter a trial depending on the condition. But for the most part, there could be some just randomness to the results where it's not as clear that it's as effective as we hoped if we did it in a much larger population. So really understanding how the trial was conducted, and for the most part, clinical trials will be presented in a meeting and eventually published in the literature where there are experts in that field who would then review the manuscript, the paper related to it, and really can kind of dissect how was the trial done and the importance of the trial and critically make sure that the results that are out there that are then used by guidelines really do reflect, hopefully, what the drug is doing for patients and how they're tolerating it and other factors.

Brielle Gregory Collins: Okay, so let's say a guideline publishes, and then new research comes out. What happens at that point?

Dr. Meyerhardt: Yeah. And there's different guidelines that are used by clinicians. So ASCO, the American Society of Clinical Oncology, puts out guidelines that are a very comprehensive review of the literature and provide all that sort of data from the literature that was reviewed. There are other groups that put out guidelines more in a little bit of a table format. And how new research gets fit in is different depending on the organization. So, for example, with ASCO, there's occasionally situations where there's already a guideline that something will change and they have different mechanisms. They have the provisional clinical opinion mechanism. So a way to sort of quickly put out something that really will change the standard and really needs to be considered as a change. There are trials ongoing constantly. And if there are things that really should be considered for patients sooner than some set time period, there's ways to help incorporate those results, and how do we think about using it for our patients?

Brielle Gregory Collins: And Dr. Tagawa, what changes or advances do you see developing in clinical practice guidelines?

Dr. Tagawa: I think that we want to retain the type of guideline that is evidence-based and will in a way, every time a change is going to be made, still start from scratch and make sure nothing is missed and be comprehensive. But at the same time, being nimble and be able to make changes, sometimes in real-time. Fortunately for physicians that treat cancer as well as our patients and their families, we're making new advances all the time. So hopefully we can match those with the evidence and produce guidelines. But then also on the user end, I'll call the user the average oncologist who may just want to make sure they're doing the right thing or sometimes is not sure what to do, to have it in a format that's very easy, sitting in the clinic about to see a patient or seeing the patients saying, "What should I do?" To have that readily available, for instance, at form.

And then even better for some of us that spend a lot—I think some of you might go to your doctor and he or she is typing on a computer. We're trying to keep up. If the guidelines are melted into what's called an electronic medical record, we just put in the diagnosis and the stage and what the patient has received before. That might pop up to, number 1, help the doctor in that situation, but also help prove that that doctor is providing what's called evidence-based medicine. So maintain the evidence base, but have it as user-friendly as possible is at least one of the goals over the next several years, hopefully.

Brielle Gregory Collins: Very nice. Thank you both so much for your time and for sharing your expertise today, Dr. Meyerhardt and Dr. Tagawa.

Dr. Tagawa: It's a pleasure.

Dr. Meyerhardt: Thank you so much.

Brielle Gregory Collins: And if you're interested in learning more about ASCO guidelines, Cancer.Net is a great place to go to find patient-friendly summaries of those guidelines.

ASCO: If this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today we're going to be talking about the psychosocial challenges unique to survivors of gynecologic cancers and how survivorship care plans can be helpful to survivors of these cancers. Our guests today are Dr. Fay Hlubocky and Dr. Merry Jennifer Markham. Dr. Hlubocky is a licensed clinical health psychologist with an expertise in psychosocial oncology and a health care ethicist at the University of Chicago in Chicago, Illinois. She is also the Cancer.Net Associate Editor for Psychosocial Oncology. Thanks for joining us today, Dr. Hlubocky.

Dr. Hlubocky: It's an honor and a pleasure to be here with all of you today. Thank you so much.

Brielle Gregory Collins: Dr. Markham is Chief of the Division of Hematology and Oncology and a clinical professor in the Department of Medicine at the University of Florida in Gainesville, Florida. She is also the Cancer.Net Associate Editor for Gynecologic Cancers. Thanks for joining us today, Dr. Markham.

Dr. Markham: Thanks so much for having me. This is going to be fun.

Brielle Gregory Collins: Absolutely. Before we begin, we should mention that Dr. Hlubocky and Dr. Markham do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to start, Dr. Hlubocky, what can survivors of gynecologic cancers expect during the transition from treatment to survivorship?

Dr. Hlubocky: It's such a very important question. So this stage of survivorship, and if we think about the cancer survivor as anyone with the time of diagnosis, but especially when your treatment ends and that kind of later stage of survivorship begins, both anecdotal reports by survivors as well as research tells us this is very much a time of ambiguity. So complicated feelings such as depression and anxiety can still arise. But there's also this change in one's life and daily activities. So from the constant monitoring and treatment that the survivor actually had to go through and be engaged in constant contact with the team, now it's a time of sometimes emptiness. Patients have told us about not really knowing what to do, missing that contact, that monitoring. And so that can certainly leave us with a lot of complicated emotional distress. But also paradoxically, there are these feelings of greater purpose and feeling and meaning leading to post-traumatic growth. Might not be immediate. As soon as, of course, the treatment ends, there can be some difficulties, even with relationships and social relationships, and we can talk about some of the psychosocial challenges, but that's what at least has been reported both anecdotally also from a research perspective.

Dr. Markham: I think that that's exactly right. I think what I see in the clinical side of the patient care is exactly that. I think a lot of people who just finished their cancer treatment don't quite know what to do with themselves. They've just been sort of released back to their lives, hopefully returning back to somewhat of a normal or a new normal life. And it's definitely an anxiety-provoking period of time. And I tend to see in the clinic room a lot of fear of what's going to happen next and what should I be doing and what should I be looking for? And also on the flip side, I think you mentioned relationships. A lot of people who I see in the exam room are telling me when they're done with treatment, I'm still having these feelings. I'm still recovering from some of my treatment experience, but my family or these friends are expecting me to just get on with life. And I'm not quite sure I know how to do that yet.

Brielle Gregory Collins: Thank you both for your perspective on this. And Dr. Markham, one of the tools someone might use during this transition is a Survivorship Care Plan. So can you please explain what a Survivorship Care Plan is?

Dr. Markham: A Survivorship Care Plan is traditionally a document, some type of a physical document or an electronic document that describes the treatment that the person has been through, describes who the physicians were involved in their care, can be very in depth, can include things like the specifics of the pathology, diagnosis, and the stage. It can also include and should include some things to look out for and what the follow up will be moving forward in the future. I think of it as really a guide and a document to refer back to so that person who receives it knows exactly what they were treated with, they know the dates of their treatment, they know who their doctors were, they know what their diagnosis and stage was. And they have a plan moving forward that they can use for their own empowerment and engagement with the health system, but also their other doctors that can utilize this as well to help know best how to monitor that patient.

Brielle Gregory Collins: Absolutely. And why do you think Survivorship Care Plans are especially important for survivors of gynecologic cancers?

Dr. Markham: I think they're important really for lots of patients, lots of people who have various cancer diagnoses. Cancer treatment for gynecologic cancers tends to be multidisciplinary, meaning that they may see a gynecologist, they may see a gynecologic oncologist, which is a surgeon who specializes in gynecologic cancers. They may also see a radiation oncologist and a medical oncologist and a genetic counselor and a psycho-oncologist. So there's so many parts to that treatment course that it can be very overwhelming. And I think for any patient who goes through such a complicated experience, not just treatment, but the whole diagnosis piece through treatment, really can benefit from having just a quick and easy reference. A summary. We also found these to be very important in times of natural disasters, for example. So someone who has lived in a hurricane zone or even in the beginning of the pandemic, it's nice to have all of your information in one easy-to-access PDF or Word document or even electronically in your email. This is really helpful for transitions and care.

Brielle Gregory Collins: Thank you so much. Yes, it definitely seems like it's a critical part of that survivorship aspect. And Dr. Hlubocky, I know you touched a little bit on the psychosocial challenges that survivors might face, but can you tell us a little bit more about some of these challenges that are unique to survivors of gynecologic cancers?

Dr. Hlubocky: Yeah. So certainly one's emotional well-being and physical well-being can be impacted. So we talked a little bit about depression and anxiety, and also sometimes folks have reported post-traumatic stress symptoms. But again, everyone's individual, everyone can vary when it comes to the mental health state. We know a recent study was conducted in Utah just last year that said, specifically, ovarian cancer patients are at a little bit more heightened risk of anxiety and depressive disorders in that longer kind of ovarian cancer survivorship phase. So that's really important for us to know. Certainly also uterine survivors as well. We have to be very conscious when it comes to mental health constraints, but there's also some physical well-being or quality of life, well-being constraints, sleep can be impacted, sleep and insomnia, pain and fatigue. We know that patients record a significant amount of fatigue as well. And that really does take time. And there are certain things, for example, exercise. But additional challenges will be with sexual health, sexual libido. We know that that changes. An altered state of self-image. Certainly, we know that cancer can impact one's self-image of who that woman is. And that as well as financial concerns might be another issue.

Dr. Markham talked about the change with family relationships and friends. They may expect you to be that person that you were before the cancer. And we know and a lot of patients have told us that it's a new normal phase for me, right? A new normal. And if we think about the cancer as being a traumatic experience, we certainly know that patients are forever changed, and it isn't necessarily for the negative. Again, there can be a lot of post-traumatic growth, a lot of resilience. And that, again, isn't necessarily going to be immediate. But certainly talking to survivors in that longer phase, we know that a lot of post-traumatic growth, a lot of meaning, a lot of purposes, a lot of impact on spiritual well-being, but it doesn't mean that one is free from stress.

Brielle Gregory Collins: And do you mind just discussing how survivors can cope with some of these challenges?

Dr. Hlubocky: Absolutely. There are a number of evidence-based treatments. For example, especially psychosocial, and then mental health treatments such as cognitive behavioral therapy, mindfulness-based reduction, using techniques like journaling, using meditation, things like this. And your psychosocial support team, if you don't have it in your cancer center, we certainly have cancer community support programs within each city. These are free community support programs where they can actually help to provide psychosocial support, either in individual or group settings. So there's lots of different modalities that could be used. Adopting breathing techniques, for example, to help address anxiety. These are the folks that can really help you teach you how to adopt some of these practices in that. So certainly there's peer support. We know peer support is a wonderful tool. At my institution, we have a peer support program. And it's really just helped both that longer-term survivor give back to a certain extent. They felt like they've gained so much being a patient and learning from that experience that they very much wanted to mentor active patients. So certainly, we know peer support, social support is very important. Individual therapy, group therapy, and that.

So don't hesitate to reach out to your psychosocial support team if it's in the cancer center. If not, talk to your oncologist or your oncology team and try to identify what are the resources within. We understand that sometimes patients don't want to come back to the hospital, and that's completely fine. We want you to get back to your life. But recognizing the fact that being a survivor is also part of this new life. So we're here to support. And empowerment is key and also recognizing that your lifestyle really focusing on exercise and nutrition and sleep is vitally important also in this new phase. But recognizing as well that we have to be cautious, that this will take time for you to adopt certain lifestyle strategies. So start with the little bits. Just even going for a daily walk if you're able to. Just daily walk around the house, so to speak. Those are the little things. And assigning yourself homework to do something just to get out of the house, so to speak. But recognizing that this will take time.

Brielle Gregory Collins: Yes. Thank you, Dr. Hlubocky. And you mentioned this term, cognitive behavioral therapy, as one of the methods for coping. Can you just describe for listeners what cognitive behavioral therapy is?

Dr. Hlubocky: Oh, sure. It's a specific type of psychotherapy where we actually target what we call automatic thoughts that can be associated, for example, with either depression or anxiety or some other mental health conditions. And we look at their core beliefs. Sometimes some thinking can be black or white. It'll never get better. Well, we know that's not necessarily the case. Maybe for that moment, it doesn't feel like it won't get better. So therapists such as myself that are trained in this modality can actually help you to identify these automatic and core beliefs and help you change them or modify them or what we call reframe them. So that's very therapeutic when it comes to healing. As well as we know, sometimes the cognitive piece can be really tough for folks. So behaviorally, it's just changing one's behavior, so to speak. So as I mentioned, exercise. Sometimes it's really easier to get people moving than it is to change one's thoughts. So prescribing exercise daily or prescriptions for social support, going out and meeting with people, these are the things that can help patients down the line, certainly in the survivorship space. And we know that folks need that. And cognitive behavioral therapy can be both done in an individual level as well as there are certain groups that can be done as well in a group setting. So everyone's different. What is your preference? You can't go wrong no matter what. It's all about empowering yourself. It's all about rewarding yourself for what you've gone through. And right now, your lifestyle is the most important thing. So you have to be a priority.

Brielle Gregory Collins: Absolutely. Thank you so much for explaining that. And Dr. Markham, are there any other survivorship challenges or any other methods of coping you want to add?

Dr. Markham: Well, it's a very complicated time and there is not one particular issue that faces each of these patients or women with gynecologic cancers. I think that the psychosocial piece is very important. And what is most important I think from my mind for the listeners is that there's a discussion about, what should I expect? And I think that question to the oncology team is really an important one. What should I expect moving forward? What should I be on the lookout for? And are there things that I can do that will help me on that path?

Brielle Gregory Collins: Absolutely. And going back to Survivorship Care Plans and using them as a tool during this transition, where can survivors go to find Survivorship Care Plans specifically for gynecologic cancers?

Dr. Markham: So amazingly, Cancer.Net has a fantastic resource available with Survivorship Care Plans. And they are very similar for various cancers. But there are some that are directly focused for women with gynecologic cancers through Cancer.Net. And it's very easy to search. You can type in "Survivorship Care Plan" into the search bar and the page will come up with these. A person can print this or can share it with their oncologist. And the cancer care team may actually be presenting this to the patient already. So there's a variety of resources really. But for someone who is interested in just taking a glance at what they may look like, there's a great template available on Cancer.Net.

Brielle Gregory Collins: Thank you so much. And thank you both for your time and for sharing your expertise today. It was so great having you both.

Dr. Markham: Thank you so much for inviting us. This was great.

Dr. Hlubocky: Absolutely. Thank you. And thanks to all the Cancer.Net listeners. We're here to help.

ASCO: If this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

[music]

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Kedar Kirtane discusses new research from the 2022 Multidisciplinary Head and Neck Cancers Symposium, held February 24-26 in Phoenix, Arizona, including research on disparities in head and neck cancer, treatment for HPV-positive oropharyngeal cancer, and strategies for reducing side effects from treatment while still keeping high effectiveness.

Dr. Kirtane is an assistant member and medical oncologist at Moffitt Cancer Center in Tampa, Florida, with a focused interest in the treatment of head, neck, and endocrine malignancies. He is also the 2022 Cancer.Net Specialty Editor for Head and Neck Cancers. View Dr. Kirtane's disclosures at Cancer.Net.

Dr. Kirtane: My name is Kedar Kirtane. I am an assistant member at Moffitt Cancer Center in Tampa, Florida. And today, I'm going to discuss some of the highlights from the recent 2022 Multidisciplinary Head and Neck Cancers Symposium held in late February in Phoenix, Arizona. For many of us, it was the first in-person meeting being attended in the last few years due to the pandemic. The talks were truly fantastic, and above all, it was nice to see colleagues, friends, and collaborators from all over. There is no way I can go over every incredible talk that was presented, but I wanted to highlight a few of the talks that I found most compelling and interesting.

So the first was the first keynote discussions by Dr. Sharon Spencer at the University of Alabama at Birmingham and Dr. Charles Moore at Emory University. They had a wonderful discussion on cancer disparities and head and neck cancers. It is unfortunately very well documented that African Americans with head and neck cancer have worse outcomes. They discussed efforts made in both Alabama and Georgia to help combat disparities in head and neck cancer outcomes for African Americans. Dr. Moore described the evolution of his interest in tackling disparities in his local communities in the Atlanta Metropolitan area, where he first held cancer screenings out of the back of his car and seeing firsthand the poverty and lack of infrastructure that contributes to the daily disparities he encounters in his clinic.

Both speakers discussed that it is imperative to increase representation of underrepresented communities into head and neck cancer clinical trials to ensure generalizability of results. And though this is very certainly easier said than done, as both speakers acknowledged, this is still an interesting aspect of clinical care that many of us encounter, where it is difficult for a variety of reasons to increase the representation of diverse communities under clinical trials. And I think this is one strong way of really doubling down and trying to combat disparities and outcomes, but I think a lot more is needed. In addition to increasing clinical trial participation, there are ways to combat implicit biases, improve local infrastructures to provide care, and engage key stakeholders for standard of care in clinical trials to minimize racial and ethnic bias. So both of these talks were really wonderful and talked about all of these things and how to incorporate them into your daily practice. As advances in the cancer world grow at exponential rates, it's really important that people from all walks of life are involved, and Doctors Spencer and Moore are doing wonderful work in their local communities and beyond to make sure this happens.

The second topic I wanted to discuss today comes from my own institution, Moffitt Cancer Center, and my colleague, Dr. Michelle Echevarria. I was not directly involved with this study, but I am obviously a colleague of Dr. Echevarria, and this study was done at my center at Moffitt. So she discussed the study that she conducted on the kinetics of circulating human papillomavirus DNA, or HPV DNA, in plasma and oral gargles from patients with HPV-positive oropharynx cancers that are treated with definitive radiation therapy. HPV, or human papillomavirus, is a sexually transmitted virus that can cause cancer. It is the same virus that causes the majority of cervical cancer, and it is actually now believed that in America, this represents the major cause for oropharynx cancers. This is in direct contrast to 20, 30 years ago where HPV as a cause for oropharynx cancers was not even known, and most of the disease was thought to be related to tobacco or alcohol. Now, there are ways to check for circulating HPV DNA in the bloodstream and also in oral gargles for patients with HPV-related head and neck cancers. This is by no means considered a standard of care, but the goal from many institutions is to try to figure out how to incorporate these blood tests in sorting out how to treat patients and potentially how to detect for recurrence. So by noninvasively being able to measure this DNA in the bloodstream, this offers potential opportunities to personalize radiation dose, i.e. for people whose HPV DNA does not go to zero initially after treatment, and also as a potential biomarker for recurrent disease.

Dr. Echevarria and her team analyzed circulating HPV in blood and in oral gargle samples from patients enrolled on a clinical trial of radiation alone for the treatment of HPV-related oropharynx cancer. And in this study, plasma and oral gargles were collected prior to the initiation of treatment. So they had a baseline HPV level in their oral gargle and/or their plasma. And they also checked it during week 4 of treatment, at the end of treatment, and then at 2 to 3 months after treatment. That latter endpoint is a clinically relevant one because many times, this is when providers are getting imaging and checking to see if the treatment that was given to the patient actually worked. And what this study found, briefly, was that a clearance of plasma HPV levels was associated with a reduction in cancer size as seen on CT imaging. And this suggests that there are future avenues for research where potentially one could study a subset of patients who immediately clear the HPV in their bloodstream early and then potentially de-escalate those therapies. So really, the question is whether those patients need the full gamut of radiation or whether they can safely avoid toxicity and at the same time maintain those high cure rates. So this was a really interesting study, and I think these sorts of studies checking for HPV in the bloodstream are going to become more and more prolific as we figure out how to incorporate this into standard of care and whether it actually ends up changing clinical practice.

Speaking of HPV and de-escalation, there was certainly a lot of discussion regarding de-escalation of therapies. Now for people who don't know what that means, what that means is that, as I mentioned earlier, HPV is a known cause of oropharynx cancers in America and abroad. And what we know now is that HPV-related head and neck cancers actually just have a better prognosis, a better cure rate, a better survival rate compared to cancers of the head and neck that are related to tobacco or alcohol. So really, the question has come up as to whether the treatment paradigm that we have, which is 6, 7 weeks of radiation, sometimes adding chemotherapy, do we really need to throw the proverbial kitchen sink at treating these patients when they already do so well?

Dr. Chera from University of North Carolina and Dr. Hayes from University of Tennessee discussed radiation and chemotherapy, respectively, in de-escalation strategies. I will say that Dr. Hayes said something really thoughtful, which is that the greatest toxicity is treatment failure, so there has to be clinical equipoise in how we choose the patients that we are safely deeming to de-escalate therapy. The last thing we want to do is decrease toxicity in the short term for patients if we don't at the same time maintain those high cure rates that are seen in HPV-related cancer patients. Dr. Chera discussed a variety of studies regarding reduced radiation dose, either after primary surgical management of head and neck cancers or as part of definitive therapy. And he conceded that while some of his treatments for his patients have changed as a result of phase 2 studies, that he acknowledged that there was a need for larger phase 3 studies to really definitively conclude that de-escalation of radiation dose is okay to do. Dr. Hayes discussed a variety of clinical trials that have been done with different chemotherapy regimens. Now the standard of care that we use is something called cisplatin. And while most of the randomized control trials have shown inferiority of non-cisplatin-based chemotherapy regimens, there's still a large future out there to figure out which subset of patients could safely either avoid chemotherapy, get a chemotherapy that is perhaps less toxic, or give a chemotherapy just with less dose. And while none of these have become yet standard of care, obviously, just like I mentioned earlier with checking HPV in the bloodstream, this is going to be a really significant part of the clinical trial landscape moving forward over the next 5 or 10 years.

So, in summary, this was a really great conference, one that focused on disparities, one that focused on HPV-circulating tumor DNA in the bloodstream and also de-escalation strategies for HPV head and neck cancer patients. So thank you for listening to this brief summary of new research in head and neck cancers.

ASCO: Thank you, Dr. Kirtane. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Greg Guthrie: Hi, everyone. I'm Greg Guthrie, and I'm a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today, we're going to be talking about the ASCO provisional clinical opinion, "Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer." Our guests today are the co-chairs of the team that wrote these recommendations. Dr. Funda Meric-Bernstam from the University of Texas MD Anderson Cancer Center in Houston, Texas. Thank you for joining us today, Dr. Meric-Bernstam.

Dr. Meric-Bernstam: Thank you for having us.

Greg Guthrie: And our second guest today is Dr. Mark Robson from Memorial Sloan Kettering Cancer Center in New York City. Dr. Robson, thank you for joining us today, too.

Dr. Robson: Thank you for having me.

Greg Guthrie: So before we begin, I should mention that Dr. Meric-Bernstam does not have any relationships to disclose related to this podcast. Dr. Robson has led clinical trials in PARP inhibitors but has not received any personal compensation for this research. Full disclosures for this podcast can be found on Cancer.Net. So, Dr. Robson, let's begin by discussing what a provisional clinical opinion is and why they are important.

Dr. Robson: So there are times when there are sea changes or incredibly important changes taking place in oncology practice. And sometimes these are clinical trial data, and sometimes they are more global. And this is a situation where it's one of those global challenges. And what ASCO does in situations like this is pull together a group of experts to provide guidance for the membership through a process of discussion and informal consensus rather than necessarily direct evaluation of clinical studies. And this is important because it allows the membership to benefit from these expert opinions.

Greg Guthrie: Now, Dr. Meric-Bernstam, this provisional clinical opinion discusses somatic genomic testing in metastatic or advanced cancer. What is somatic genetic testing, and how is it used in cancer treatment?

Dr. Meric-Bernstam: Oh, thank you. This is a really exciting time in the last decade. We have a lot more tools to understand cancer biology. And cancer is a genomically-driven phenomena, where there's alterations in the DNA, in the tumor, that confers the cancer cells a competitive growth and survival advantage. And only 10 years ago, we had the capability of doing this 1 gene at a time, to sequence a gene to see what is different, but now we have technologies where we can look at several hundred genes at a time. We are referring to these as multigene panels. And we're talking about genomic testing or somatic genomic testing. These are tests that look at several hundred genes, either looking at the tumor sequence alone or looking at the tumor sequence and comparing it to the normal sequence so we can see what has differed in the tumor that may give it a competitive advantage. We're doing this to be able to identify if there are genes that are altered that are therapeutically actionable. What we mean by that is, is there an alteration that we think confers the cancer cell an advantage for which we have a drug that either directly or indirectly we can use to help inhibit the cancer cell growth or preferably cause the cancer cell death?

Greg Guthrie: Great. And so how is somatic testing different from germline testing?

Dr. Robson: So somatic testing is testing the DNA or the nucleic acids, if you will, in the tumor itself, and germline testing is testing the DNA in normal tissue. And so the DNA in the normal tissue is what people are born with, and of course, most of the DNA in the tumor is the same as what people were born with. But there are specific changes that develop as the cancer arises, and it's those specific changes that are called somatic alterations.

Dr. Meric-Bernstam: This is actually a really interesting point though because some tests report out germline alterations as well because only the tumor is sequenced, while some tests report the tumor, only subtracting what was in the germline. Thus, unless the germline result is specifically reported, a patient that has a known germline alteration may be surprised to see that it's not in the tumor report. And on the flip side, a tumor-only test may find a germline alteration, and thus it's important that physicians and patients are aware of that. That needs to be further pursued with the genetic testing.

Greg Guthrie: Wow, just a wealth of information coming from this testing now. Sometimes I hear the term next-generation sequencing mentioned in regard to cancer. Does this provisional clinical opinion also touch on that?

Dr. Meric-Bernstam: Yes. When we are referring to genomic testing panels or multigene panels, we are talking about the next-generation sequencing technology that has the ability now to use a small amount of tumor to be able to report out the sequence of several hundred genes. We have, of course, broader panels also coming, such as whole exome sequencing, whole genomic sequencing. Although, majority of our provisional clinical opinion is talking about the use of these in several hundred gene panels.

Greg Guthrie: Amazing. Alright. Dr. Meric-Bernstam, so what should people with cancer and their loved ones know about this opinion?

Dr. Meric-Bernstam: This has been a really complicated time because the introduction of next-generation sequencing made genomic testing available, but to be fair, not widely available initially. Only more recently is it more broadly available, and there's been some confusion about which patients with which diseases should get or can get genomic testing or would benefit from genomic testing. So we wanted to frame this by first highlighting that if a patient has a metastatic or advanced cellular tumor type and there is a genomic biomarker that is linked to a therapy approved for a regulatory agency, or they have a tumor type where there's a drug that's approved but there's a known genomic resistance marker, these are scenarios where we feel patients should get genomic testing. Now, the more complicated area, a little more controversial, has been scenarios where the patient has a disease that is not one of those diseases that has a disease-specific approval for a drug. And in that scenario, we believe there's still value in genomic testing for several reasons.

There's been several new drug approvals for what we call tumor-agnostic drugs. That means if you have an alteration that gives you sensitivity to immunotherapy because you have what we call microsatellite instability, and some next-generation sequencing panels can report that out, then, regardless of your tumor type, you may be able to get offered immunotherapy. If you have multiple mutations in your tumor, something we call the increased tumor mutation burden, that is now linked to immunotherapy approval. So irrespective of tumor type, if a patient is eligible for immunotherapy, they benefit from getting genomic testing. And then on top of that, we now are seeing more and more that patients may have a genomic alteration that we think is a compelling target. But they may have it-- they may have it in a disease where that drug was not approved. And we're now starting to see that in many clinical trials. We're seeing activity by targeting those alterations. So there may be additional opportunities, especially for clinical trial enrollment, by identifying these potentially actionable alterations in other diseases.

So taking this together, we believe multigene testing will provide both additional approved indications and clinical trial indications. And in addition, fusion testing can identify TRK fusions, a fusion type that's found commonly in some uncommon cancers and uncommonly in some common cancers. But when it's found, it is a very compelling target. So again, because patients would be eligible for TRK inhibitors, irrespective of their tumor type, that's another scenario where next-generation sequencing may be beneficial for patients with advanced and metastatic disease, irrespective of tumor type.

Greg Guthrie: Wow, that's just an amazing overview right there. And one question that occurs to me is, is all of this genetic testing done from a biopsy sample? Or are there other ways a patient may experience this testing?

Dr. Meric-Bernstam: The traditional tumor-based testing is usually done either from a surgical sample or a biopsy sample. And again, it could be tumor-only testing or tumor plus a normal. Usually, normal would be something like blood as a comparator. However, there are times where a patient doesn't have a tumor accessible for a biopsy. In that scenario, there is now the opportunity to look at circulating free DNA to do panel testing on circulating free DNA for some of the more common actionable alterations. So there's a lot of momentum in using that approach, and this is what we often refer to as a liquid biopsy. And the liquid biopsy strategy is also very interesting because it's another way to pick up what changes of the tumor with treatment as well. So there's a lot of research going into using liquid biopsies when the patient also progresses on targeted therapy to see what has changed and how we need to change our therapy to address the tumor's evolution.

Greg Guthrie: Wow. Thanks for that, Dr. Meric-Bernstam. Dr. Robson, what are the emerging ways that genetic testing may be used to help people with cancer?

Dr. Robson: I think there are many, many ways. I was reflecting on this question, and I think it's important to kind of separate, as we did earlier, what we mean by genetic testing, again, because I think there's a lot of confusion. And there's certainly a lot of work going on in terms of testing of inherited DNA, so germline testing, to identify risks for cancer and potentially therapeutic targets. And that's not something that was discussed in this particular opinion, but it is an important way that genetics is being used to help people. On the side of the folks who already have cancer, the application of genetic technologies, as Dr. Meric-Bernstam said earlier, is identifying more and more targets. In other words, more and more alterations that are driving the cancers and for which we can test new drugs and hopefully achieve successes in a much more focused and less toxic way. And that work is going on at an exponential pace, and indeed, perhaps most of the new drugs that are entering the development pathway right now are indeed targeted therapies, not conventional broad-spectrum chemotherapies.

The genetic technologies are also being used as, again, Dr. Meric-Bernstam said, to look at DNA from the tumors that are circulating in the bloodstream. And one way is the liquid biopsy, which is for characterization. But another way that's coming online is just simply to look for the presence or absence of circulating DNA in people who are, for instance, post-op and don't have any evidence of disease to see whether or not they might, in fact, have some cancer that hasn't been detected by imaging. And then the hope is that we could then intervene earlier in that setting and perhaps prevent those circulating DNA from representing true metastasis, detectable metastasis. And again, a lot of work going on there. And there's a diagnostic and prognostic component to what's happening as well. There are, unfortunately, a number of people who present with metastatic cancer, and it's not obvious at all where that started. And work is being done now to use testing of the tumor DNA to help categorize the tumors, to direct the correct therapies, instead of just doing something generic and empiric. And there are many, many other ways that genetic technologies are being applied. It's really 1 of the 2 big frontiers in cancer therapy right now. The other one, of course, being immunotherapy. But it is an exciting time, and I think it's just going to continue to grow as the technologies become more and more innovative.

Greg Guthrie: That's really exciting. And thank you for sharing all of that perspective. I really wonder if helping with this somatic testing can help increase enrollment in clinical trials, too, to advance progress in other rare cancers?

Dr. Robson: I think it did, not necessarily just in rare cancers. I mean, people are—

Greg Guthrie: Agreed.

Dr. Robson: —certainly doing testing in common diseases and identifying these new targets. And you're exactly right. The only way we're going to be able to develop new therapies in that setting is through clinical trials. And so, for the appropriate people, genetic testing or testing of the tumor or somatic testing could very well identify clinical trial opportunities for them, and that's the way we're going to move forward.

Greg Guthrie: Outstanding. And again, I really love this distinction between somatic and germline testing and clarifying that for our listeners today. Dr. Meric-Bernstam and Dr. Robson, thanks so much for your time today and for sharing your expertise on these ASCO recommendations. It's been great having you and chatting with you today.

Dr. Robson: Thanks.

Dr. Meric-Bernstam: Thank you for having us.

Greg Guthrie: And for our listeners, if you'd like to learn more about genetics, genetic testing, and cancer, visit www.cancer.net/genetics. Thanks so much for joining us today, and be well.

ASCO: If this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Christopher Flowers covers highlights from the 2021 American Society of Hematology Annual Meeting, held December 11 to 14 in Atlanta, Georgia. He discusses new treatments for diffuse large B-cell lymphoma, advances in immunotherapy, and a session on improving inclusivity in clinical trials.

Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and was appointed Division Head ad interim of Cancer Medicine in August 2020. He is also the 2022 Cancer.Net Associate Editor for Lymphoma.  

View Dr. Flowers' disclosures at Cancer.Net.

Dr. Flowers: Hello. I'm Dr. Christopher Flowers, Chair of the Department of Lymphoma and Myeloma and Interim Division Head for Cancer Medicine at The University of Texas MD Anderson Cancer Center. And it's my pleasure to talk to you today about the highlights from this year's American Society of Hematology meeting. The ASH meeting this year was a very exciting meeting for lymphoma broadly across all of the lymphomas, with particular highlights around diffuse large B-cell lymphoma where there were some changes that may be changes in the standard of care in the year ahead. I was involved in one of these studies, the POLARIX study that I'll spend some time talking about, where I was the North American lead, and I've served as a consultant for Genentech-Roche in the conduct of that study and other studies related to drugs in their portfolio. The other set of studies that I will talk about are the studies around CAR T-cell therapy. And 2 of those studies, Dr. Jason Weston from my institution and MD Anderson were involved with and Dr. Weston was the senior leader on 2 of those 3 studies that I will talk about.

So let's first talk about the first line in diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma, as many of you may be aware of, is the most common type of lymphoma and the most common type of aggressive lymphoma. Back in the 1970s and 80s, the standard of care for CHOP therapy was developed. And that through the 90s, through a number of comparisons of clinical trials for chemotherapy, emerged as the de facto standard of care. In early 2000, the drug rituximab, the anti-CD20 antibody therapy, so our first form of immunotherapy, was added to CHOP. And R-CHOP therapy became the standard of care around 2002. And so it's really been about 20 years that that has been the standard of care for all patients or for most patients in the front line for diffuse large B-cell lymphoma. That's not been without challenges. There have been a number of clinical trials from 2002 to the present that have challenged R-CHOP, either by adding new therapies, like new targeted therapies looking at intensifying the CD20 antibody component, adding things like stem cell transplant or intensifying the chemotherapy-- and in some cases, focusing on subsets of diffuse large B-cell lymphoma, like the activated B-cell-like subset that are at poorer outcomes in the general population. However, none of those clinical trials really emerged to change the standard of care. And R-CHOP had remained the standard of care for patients.

This year, as one of the late breaking abstracts presented at the American Society of Hematology meeting and followed up by a publication in the New England Journal of Medicine, one of our top premier journals, there was a study that looked at the substitution of vincristine, one of the drugs in CHOP, for the drug polatuzumab vedotin. Polatuzumab vedotin is what we call an antibody-drug conjugate, where that antibody binds to a cell surface marker on the lymphoma cells CD79B. And with that, binding is internalized into the cell. And the conjugate is a form of chemotherapy, MMAE, that is then taken into the cell with the antibody. And that antibody-drug conjugate was substituted for vincristine in the study. In the POLARIX study, it showed that it met its primary endpoint for the study, which was an improvement in progression-free survival, where the patients who got the polatuzumab in their chemotherapy with R-CHP had an improvement in progression-free survival of approximately 26% over the group that got R-CHOP. This is the first time to show an improvement in front-line therapy for patients with diffuse large B-cell lymphoma. And regulatory bodies will be looking at this to see whether this is approved in the first line in the relatively near future.

The other major trials that were presented at this year's American Society of Hematology meeting in diffuse large B-cell lymphoma were trials looking at the second line of therapy for patients with diffuse large B-cell lymphoma. And in that second line, for patients who were fit and able, stem cell transplant has formed as standard of care for patients after R-CHOP therapy. As many of you may know, diffuse large B-cell lymphoma is a disease where the goal of treatment is cure. And with that first-line therapy, the therapies that are able to produce benefits in terms of progression-free survival are expected to go on to cure for those patients if those responses are durable in 5 years. Even when patients have relapse after their first-line therapy, there's the potential of cure in the second line. And stem cell transplant has been that curative approach that we've taken for many patients in the past.

In this year's ASH meeting, there were 3 trials that compared the concept of moving on, after first-line therapy, to intensive chemotherapy followed by a stem cell transplant or to performing CAR T-cell therapy as that second-line therapy. As some of you may know, CAR T-cell therapy has emerged as really an exciting form of immunotherapy, a cellular therapy, that is approved for patients who are with lymphomas and some leukemias and being explored in other diseases. CAR T-cell therapy is a form of immunotherapy where we actually re-engineer cells. So we take the cells from the patient and then genetically re-engineer those cells so they attack a marker on the cell surface. I talked about CD20 antibody therapy. All of these CAR T-cell therapies are cellular therapies against the marker on the lymphoma cells called CD19.

And so in these 3 trials that compared CD19 CAR T-cell therapy versus autologous stem cell transplant, 2 of those trials, 1 presented in the plenary session—and that was one of the ones that Dr. Weston participated in—was a study that showed that there was a benefit in progression-free survival for those patients who received CAR T-cell therapy over the approach to do stem cell transplant as that second-line therapy. There was a second trial, the TRANSFORM trial, that was also presented in one of the oral abstract sessions. That one presented interim analysis of their trial. They also showed a benefit in terms of progression-free survival. And then there was a third trial that was looked at in the late breaking abstract session. That one did not show a benefit for CAR T-cell therapy in that setting, using  tisagenlecleucel as a form of CAR T-cell therapy in that study. And perhaps the reasons why that did not show a benefit or differences in the trial design between those 3 trials, not as many of the patients were able to go on to CAR T-cell therapy in that third trial. And that was really expertly described and compared by Alex Hariri in a discussion of the plenary session. So really, 4 major trials in diffuse large B-cell lymphoma that we expect will change the standard of care.

Likewise, there were a number of other exciting new immunotherapies that have been presented at this year's annual meeting, namely studies looking at bispecific antibodies. And so these are antibody-based therapies in a number of different trials that both engage a portion of the lymphoma cell. And then as the other portion of the bispecific, so meaning two, that other portion engages T cells. So it brings T cells into the tumor to be able to attack the lymphoma cells. And so there are a number of exciting therapies that are on the horizon for lymphomas looking at that. And those were also presented at the ASH meeting.

The last thing that I'd like to highlight from this year's annual society meeting was a joint session that looked at the role of clinical trials and ways that we can actually improve clinical trial design for patients-- 1, to increase the diversity, equity, and inclusion that we see across clinical trials to make sure that all patients who are eligible are having equal access to trials and being able to participate, but also in terms of being able to modify the eligibility criteria that we use for clinical trials. One of the things that we've explored, particularly for those challenges that I described without advances in the front line for diffuse large B-cell lymphoma in the past, have been that some of the eligibility criteria for our past trials really were not including all the patients who were most likely to benefit from trials. And so Tom Witzig at this year's annual society meeting really presented an outstanding look at the eligibility criteria that we use for lymphoma trials, and trying to be able to address those in ways that help to allow more patients to participate in trials, and those who are most likely to need a trial to be able to benefit from the activities that are engaged in a trial.

So I really appreciate all of your attention to this podcast. Exciting meeting this year for the American Society of Hematology Annual Meeting. And lots of things that will come to patients in the near future. And hope to be able to create advances that will help all of you in terms of your quality of life and well-being. So thank you all for your attention.

ASCO: Thank you, Dr. Flowers. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests statements on this podcast do not express the opinion of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Norah Lynn Henry will discuss new research presented at the 2021 San Antonio Breast Cancer Symposium, held December 7-10. Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center in Ann Arbor, Michigan.

View Dr. Henry's disclosures at Cancer.Net.

Dr. Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. I'm here with exciting updates from the leading international breast cancer meeting, the San Antonio Breast Cancer Symposium, that was recently held in San Antonio, Texas, and online. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both metastatic and early- stage breast cancer. Then to wrap it up, I'm going to mention an interesting study looking at lymphedema. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive, and are stimulated to grow by the hormone estrogen. We treat those cancers with antiestrogen treatments, which block estrogen or lower estrogen levels. Other breast cancers are called HER2-positive. These are often more aggressive cancers, but because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or HER2. These are called triple-negative breast cancers and are also often aggressive cancers. So first, I'm going to talk about treatment for HER2-positive metastatic breast cancer. Many of the treatment regimens that we use for treating patients with HER2-positive breast cancer include the antibody trastuzumab, which is also called herceptin. More recently, 2 drugs have been approved that include trastuzumab linked to a chemotherapy drug. So they're sort of like smart drugs. One is called trastuzumab emtansine and the other is called trastuzumab deruxtecan. In the DESTINY-Breast03 trial, which was presented earlier this year, the deruxtecan drug was shown to be more effective than the emtansine one.

At this San Antonio meeting, the investigators look specifically at how well these 2 drugs worked in patients whose breast cancer had spread to their brain. And these exciting results, the deruxtecan drug was shown to greatly lengthen the time until cancer worsens compared to the emtansine drug, from 3 months on average to 15 months. In addition, on brain MRI, almost two-thirds of the patients had shrinkage of the brain lesions when they received the deruxtecan drug, compared to only about one-third who received emtansine. These important findings give us yet another potential treatment that we can use to help patients who have HER2-positive breast cancer that has spread to their brains.

So next, I'm going to switch gears and talk about treatment of metastatic hormone receptor-positive breast cancer. At this time, the initial treatments are generally with antihormone drugs, such as aromatase inhibitors or fulvestrant. Unfortunately, these drugs often stop working, and then patients have to switch to chemotherapy medication. The good news is, that there are a number of new antihormone drugs currently being developed in the EMERALD trial, which was presented at this meeting. Investigators tested a new antihormone medicine called elacestrant in postmenopausal women with metastatic breast cancer whose cancer had previously worsened during treatment with medicines called CDK4/6 inhibitors plus antihormone treatment. These findings are exciting because this new drug may work against some cancers that no longer respond to a currently available antihormone medicines. It might mean they don't yet need to switch to chemotherapy. However, the findings are still early, and this drug is not yet approved by the FDA. I'm sure we'll hear more about this drug and other similar ones in the months and years to come.

There were a lot of other research findings presented related to treatment for early- stage breast cancer at the meeting. And there were quite a number of updates from studies that were previously presented. For example, in patients with stage 2 and 3 triple-negative breast cancer, adding immunotherapy to neoadjuvant chemotherapy, which is chemotherapy given before surgery, improves event-free survival. Similarly, updated results from the RxPONDER clinical trial confirm that it is okay to not to give chemotherapy to postmenopausal women with hormone receptor-positive HER2-negative breast cancer who have 1 to 3 involved lymph nodes, and a 21-gene recurrence score of 25 or less.

Finally, there was a report of a large clinical trial examining whether the diabetes drug, metformin, can decrease the risk of breast cancer recurrence, especially in hormone receptor-positive breast cancer. Unfortunately, taking metformin did not lower the risk of breast cancer recurrence compared to placebo. So it is not recommended that patients take this drug specifically to try to lower their risk of breast cancer coming back.

In addition to these studies reporting findings about new medications, we also learn new information about an old problem, lymphedema. A group of women were followed over 2two years after they were diagnosed with breast cancer and underwent axillary lymph node dissection or removal of a large number of lymph nodes from under their armpit. Using a specific type of lymphedema measurement that looks at swelling in the arm, they found that almost 1 in 10 patients had developed lymphedema within 1 year of surgery, and almost 1 in 4 had lymphedema within 2 years. These are similar to what other studies had previously found. But importantly, patients who were Black were much more likely to develop lymphedema compared to white or Asian patients. This association with race hadn't been carefully looked at before and suggests that additional studies need to be done to figure out how best to monitor for, prevent, and treat lymphedema in all patients with breast cancer.

Importantly, at this meeting, we also got glimpses of the many new drugs on the horizon for the treatment of breast cancer. And we eagerly await the results of large randomized trials so that the drugs at work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2021 San Antonio Breast Cancer Symposium. Overall, we continue on a fast track in breast cancer with many new and exciting therapies being actively studied, as well as research helping support our patients to do better than ever. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you.

ASCO: Thank you, Dr. Henry. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, experts will discuss targeted therapy for lung cancer, including 2 new treatments that target a specific type of mutation or change in the EGFR gene in some cancer cells, called an EGFR exon 20 insertion. They will explain how targeted therapy works to treat cancer, why this specific mutation is different from other, more common EGFR mutations, and what these 2 new treatments mean for people with this type of cancer.

This podcast will be led by Dr. Charu Aggarwal, Dr. Xiuning Le, Dr. Vamsidhar Velcheti, and Marcia Horn.

Dr. Charu Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the Cancer.Net Associate Editor for Lung Cancer. 

Dr. Xiuning Le is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Internal Medicine at the University of Texas MD Anderson Cancer Center in Houston, Texas.  She is also a Cancer.Net advisory panelist for lung cancer. 

Dr. Vamsidhar Velcheti is the director of thoracic medical oncology at NYU Langone's Perlmutter Cancer Center in New York, New York, and is also a Cancer.Net advisory panelist for lung cancer.

Marcia Horn is the President and CEO of the International Cancer Advocacy Network and the executive director of the Exon 20 Group in Phoenix, Arizona. 

View full disclosures for Dr. Aggarwal, Dr. Le, Dr. Velcheti, and Ms. Horn at Cancer.Net.

Dr. Charu Aggarwal: Hello and welcome to this Cancer.Net podcast on new research in lung cancer. I'm Dr. Charu Aggarwal from the University of Pennsylvania. I'm also the Cancer.Net Associate Editor for Lung Cancer. I'm here today with my colleagues from the Cancer.Net Lung Cancer Panel. First is Dr. Xiuning Le from the University of Texas MD Anderson Cancer Center. Hi, Dr. Le.

Dr. Xiuning Le: Hi, everyone. This is Xiuning Le from MD Anderson. I'm happy to be here as one of the discussants.

Dr. Aggarwal: Next is Dr. Vamsi Velcheti from the NYU Langone Perlmutter Cancer Center. Vamsi?

Dr. Vamsidhar Velcheti: Hi, this is Vamsi Velcheti. I'm so glad to be here with you.

Dr. Aggarwal: And our special guest today is Marcia Horn, the president and CEO of the International Cancer Advocacy Network and the executive director of the Exon 20 Group. Hi Marcia.

Marcia Horn: Hi, everyone. Wonderful to be here.

Dr. Aggarwal: So good to have you all. Before we begin, we should mention that Marcia has consulted with both Takeda Oncology and Janssen on survey research for the Exon 20 Group. You can view full disclosures for this podcast at Cancer.Net.

Our podcast today is going to be about targeted therapy for non-small cell lung cancer, and specifically, 2 new treatments that target a specific type of mutation or change in the EGFR gene in some cancer cells. This mutation is called an EGFR exon 20 insertion. Dr. Velcheti, I'll start off with you. What is targeted therapy, and how does it work?

Dr. Velcheti: So thank you, Charu. Lung cancer is a very complex biological disease. There are a lot of genes in the tumor cells that could be mutated, and understanding the type of genetic changes or mutations in the DNA of these tumor cells helps us really develop treatments that are very focused on that particular patient's cancer. Having a specific gene alteration could render tumors more susceptible or vulnerable to certain treatments, and these are what we call targeted therapies. And in lung cancer, these are especially important because there are a lot of drugs developed for patients with certain unique genomic aberrations, or changes in the DNA, and it's ushered in a whole wave of new treatments for patients with lung cancer, and it's really an exciting time for patients with lung cancer.

Dr. Aggarwal: That's terrific. And I would like to focus on the mutation aspect a little bit more. Dr. Le, can you talk to us [about] whether all mutations found in lung cancer, can all of them be treated?

Dr. Le: Like Dr. Velcheti was talking about, lung cancer is really a complex disease. And oftentimes in 1 lung cancer, we can detect more than 1, multiple mutations. Some of them function as driving the cell growth. Some of them function as a brake. We call that a tumor suppressor to release the cell from being suppressed. Clinically, we usually classify all the mutations that can be detected in the lung cancer into the 2 groups. One is called actionable. The other group is called not actionable. Actionable, meaning when we detect a mutation, we, as clinicians, can actually offer a specific targeted therapy to act on the mutation. Therefore, detection of the actionable mutation oftentimes translates to the patient potentially having the opportunity to get targeted therapy targeting that potential actionable driver oncogene. As of today, we're talking, the development of lung cancer treatment has been so advanced. We have 9 actionable genetic alterations that can be detected in non-small cell lung cancer. Even since 2 years ago, there are 4 new additions, so a total of 9 as of today, and EGFR exon 20 is one of the newest being approved in 2021, so really good news.

Dr. Aggarwal: I know we've come a long way, and EGFR exon 20 insertions have been known for a long time. However, we've also known that they are not perhaps as sensitizing as the other EGFR mutations. Dr. Velcheti, could you shed some light on what is unique about these mutations in terms of testing as well as application of therapies?

Dr. Velcheti: We have known about EGFR mutations in lung cancer for a very long time, and there have been quite effective treatments for EGFR activating mutation-positive lung cancer patients. However, not all mutations in the EGFR gene are the same. Depending on the location of the sequence change in the gene, they could have a different degree of response to EGFR inhibitors. So when we talk about EGFR exon 20, we're talking about a subset of these EGFR gene mutations which is in an area of the EGFR gene, a change in the sequence of the EGFR gene, that doesn't necessarily respond so well to the novel EGFR inhibitors that we have been using for a long time.

So the clinical implications, and it's something to kind of think about and remember, is that the way we test for these mutations is very different. You could do comprehensive genomic profiling, or in some cases, there are some tests that actually test for a specific type of gene mutation. So it's something we call "hotspot panels." Those are tests using certain techniques that actually only pick up certain EGFR genes, and they don't pick up all the gene mutations that happen in the EGFR gene. So it is very important to kind of keep that in mind because now we have drugs approved for exon 20 mutations. If you don't actually pick them up on a test, then obviously, we can't identify those patients for treatment with these exciting new treatments.

And also, just as a quick plug, given that we have so many new drugs approved for different types of gene alterations in lung cancer, it is even more important now to focus on doing really good biomarker testing with comprehensive genomic profiling looking at a wide panel of genes, rather than focusing on certain kinds of gene mutations. So this is what we call comprehensive genomic profiling. That's absolutely critical in order to identify patients for the right treatment with targeted therapy. So it's extremely important to do that upfront so that we have patients kind of matched up to the right treatment.

Dr. Le: I do also want to add with Dr. Velcheti in that I fully agree that exon 20 is oftentimes not on the hotspot PCR-based testing, so please use a comprehensive, what we call, next-generation sequencing base. I also want to say that also, exon 20 can be detected in liquid biopsy. So it's not you have to do the tissue biopsy if the patient has the opportunity to get liquid biopsy. As long as it's a good, comprehensive panel, it should also be able to detect that.

Dr. Aggarwal: Absolutely, can never underemphasize the benefits and importance of comprehensive testing. Marcia, I'll turn to you. You lead a large group called the Exon 20 Group. How common is the EGFR exon 20 insertion-- how common is this mutation in people with lung cancer?

Marcia Horn: It's not at all common. In fact, EGFR exon 20 insertion mutations in non-small cell lung cancer are exceedingly rare, a total of about 2% of all NSCLC and about 9 to 10% of all EGFR mutations. And it's an insertion mutation that hits, for the most part, never-smokers and members of Asian populations, although we at the Exon 20 Group have seen diagnoses in virtually every racial and ethnic group imaginable.

The Exon 20 Group was established in 2017 as a special project of ICAN. It was founded by an EGFR exon 20 insertion patient, Kevin Hamlin, and his brother, Bob Hamlin, who's a senior lecturer at MIT. What we all wanted to do was get an international working group put together, and before we knew it, we had this huge global coalition of not only many hundreds of patients for EGFR exon 20 insertion and HER2 exon 20 insertion representing about 54 countries, but we had care partners, family members, several hundred leading thoracic oncologists, medical oncologists, and members of the community oncology setting as well, plus biotechs, pharmas with drugs in the exon 20 pipeline, and members from molecular profiling labs and the basic sciences in exon 20 bench science.

So altogether, we're working to turn this into a chronic and manageable disease, and for the last 4 and a half years, we've been connecting our patients to promising clinical trials, especially the 2 newly approved drugs, and our angel buddy program provides our patients with peer-to-peer counseling to help them through side effects. So we're all united in blasting this disease off the planet and making the patient journey far more manageable.

Dr. Aggarwal: Incredible. I'm just so proud of what all you've achieved, and you serve such an important mission in terms of patient advocacy and, more importantly, support. Dr. Velcheti, there have been 2 new recently approved targeted therapies to treat non-small cell lung cancer that harbors an EGFR exon 20 insertion mutation, and really, these drugs have come to us within the last few months. How does the first drug, mobocertinib, work to treat this cancer?

Dr. Velcheti: Yeah, definitely. I think this is a really exciting time for thoracic oncology as we have more to offer our patients, especially for exon 20 and EGFR exon 20 specifically. We have 2 drugs now, FDA-approved, and mobocertinib is a small-molecule inhibitor. It's an oral drug, and this has been approved for patients who have EGFR exon 20 mutation. This is for patients who have already had platinum-based chemotherapy, and they have progressed, and these patients could now be treated with mobocertinib. Certainly, the activity, it seems like a very active drug. It's very promising. It's kind of similar to the other small-molecule targeted therapies that we have, but it does have side effects. Patients could potentially have diarrhea, which is kind of similar to other EGFR small-molecule inhibitors or drugs in the class, so it's something to kind of know when patients are being treated with this drug. Certainly, it's really nice to have more treatment options for these patients. So I think now we haven't had any EGFR small-molecule inhibitors show significant efficacy in this patient population, so this is a really welcome approval for patients. And there's also a new drug, which I'm sure Dr. Le is going to be talking about, amivantamab, which could also be an option for these patients.

Dr. Aggarwal: Speaking of, let's turn to Dr. Le about amivantamab. Can you tell us a little bit more?

Dr. Le: Yeah, amivantamab, again, represents a very exciting approval. I think, like Dr. Velcheti was talking about, the small-molecule inhibitor, but amivantamab represents a brand-new class of potential agents for exon 20 and many other oncogene targets in lung cancer.

So amivantamab, as the name signifies, is an antibody drug. It's not an oral drug. It's an IV drug. The antibody has 2 heads, basically. One is targeting EGFR. The other is targeting another oncogene called MET. So it's a bispecific antibody. The mechanism of action is also different than the small-molecule inhibitor such as mobocertinib in that it's not disabling the ATP-binding kinase activity of EGFR, rather than its antibodies to go after the EGFR on the cell surface and disable or internalize the receptor a different way. So I say that we're excited because it represents a really brand-new group of targeted therapy that we're probably going to see coming in the next decade, not just limited to the small-molecule inhibitor, of course, from the research, and also opens opportunity for future combinations.

In terms of usage, so again, this medication is approved in patients who have EGFR exon 20 insertion, who had prior treatment. It's an IV treatment, and then the IV is rather frequent, every 2 weeks. The drug showed really great safety and then induced response in about 40% of the patients, a nice addition to the tools we have that we can battle the disease.

Dr. Aggarwal: It's amazing that we have 2 drugs in this space. Can you talk, in your personal experience, pros and cons of each approach and if there is any data to guide using 1 drug versus another or in sequence? We'll start with you, Dr. Le, and then we'll go to Dr. Velcheti.

Dr. Le: Yeah. So that's a very good question. I don't think we have the 1 perfect answer because we haven't conducted either head-to-head trials or sequential trials. When I'm in my clinic, I tell my patients that both of them are valid options. And most likely, 1 patient will be receiving 1 and the other because I think each of the medications also have a limit of after a certain time, the disease will continue to progress. So we shouldn't be ruling out either of them rather than thinking of them as being the sequential treatment. One thing I do also discuss with the patient is the drug administration - one is IV; one is oral - and then toxicity profile. The amivantamab, the most common issue is the infusion reaction in the first time that the patient's receiving it. However, after that's properly managed, the drug is really easy to tolerate down the line. So usually, I present both options to patients. I would have to say that numerically speaking, the response rate of amivantamab is higher than the reported of mobocertinib. So sometimes, together with the patients and family, we decide to go for amivantamab first and then save oral TKI as the next option, but really, there's no right or wrong. And then I tell the patient most likely, they will be receiving both in the end.

Dr. Aggarwal: Your thoughts, Dr. Velcheti, on that approach? Anything different that you do?

Dr. Velcheti: No, I completely agree with Dr. Le. Both of them are very different drugs. So Dr. Le mentioned they work in very different ways. They have, most importantly, very different adverse event profile. So we don't know about what the right sequencing should be. We don't have those studies to really inform us. But I do the same thing that Dr. Le just mentioned. Given slightly higher response rates, we tend to use amivantamab first, but again, it's really patient preference. I've had patients who said they don't want to have IV infusions. They prefer oral treatment. They don't want to come into the hospital that often. And there are some patients who are really concerned about the diarrhea. So it's really hard to kind of know what would be the perfect sequence, and especially, it's a rare population, so it's going to be really hard to do a trial, to kind of do a cross-trial comparison. That's all we have here in terms of making decisions.

The other thing to also consider is, do we use these 2 drugs, one after the other, if they progress? I think given that they work in a very different way mechanistically, I do think if you progress on mobocertinib that doesn't necessarily mean you will not respond to amivantamab and vice versa. So I would encourage trying sequential approach. And also the other thing to also keep in mind is there are a lot of clinical trials with exciting drugs which are in the pipeline, and, of course, some of the data has already been presented and those look really promising. So I highly encourage patients to kind of consider participating in clinical trials.

Dr. Aggarwal: That's such a fantastic summary. And Marcia, I will turn to you. What do these new drugs mean for patients with this rare subset of an actionable mutation?

Marcia Horn: I totally agree with Dr. Le and Dr. Velcheti and their comments based on their deep, deep experience with EGFR exon 20 insertion patients. No question that, from the point of view of the Exon 20 Group, we were totally thrilled at the FDA approvals of both amivantamab and mobocertinib. And we, like everyone else, affectionately call both drugs as ami and mobo. These drugs are providing a concrete lifeline of hope, for the first time, that patients' lives can be extended and patient journeys can be manageable in terms of side effects. So what we're really excited about in the Exon 20 Group is not only the continuing clinical development of ami and mobo and other promising drugs in the pipeline, as Dr. Velcheti said, but we're looking forward to seeing ami and mobo in combination with second drugs. We're awaiting data down the road, obviously, from the ongoing amivantamab plus lazertinib trial that is recruiting, in part, EGFR exon 20 insertion patients, and we're really excited about drugs that can be combined with mobocertinib as well. We want a robust pipeline of numerous choices and good compounds.

Dr. Aggarwal: And Marcia, given the amount of information in this subgroup, what questions should patients ask their doctors about these new treatments?

Marcia Horn: We really think it's important for patients on diagnosis to ask their clinicians what the method of communication is going to be between patient and physician. This is not only important on diagnosis of EGFR exon 20 insertion mutated cancer, but it's really, really important when the patient is accessing either ami or mobo or a drug in clinical trials. So patients need answers on who is going to be answering their questions about side effects when they write those questions into a patient portal, and they have to have the sense that somebody is going to be listening to them in the event that the collateral medications that an oncologist may be giving them in conjunction with a clinical trial drug or in tandem with either ami or mobo-- if those collateral medications are not tamping down on side effects to the extent that we all want to see, we, for sure, want that patient to be talking to the treatment team, the study team, or whoever, and getting some quick answers because frankly, nothing is more tragic than a patient withdrawing from a drug for failure to manage toxicities, and we never want to see that happen. We do everything possible at the Exon 20 Group to make sure patients are outfitted with angel buddies who have lived, battle-hardened experience with that particular drug, and these drugs are manageable.

Dr. Aggarwal: So much excitement going on in this space, and we are thrilled to be able to offer these approaches. But I will just summarize that we wouldn't be able to extend these benefits if we don't test, and comprehensive testing remains critical in diagnosing and delivering appropriate therapy. Thank you so much, Dr. Le, Dr. Vamsi Velcheti, as well as Marcia, for joining us today for this Cancer.Net podcast. You can learn more about lung cancer and how it's treated by visiting Cancer.Net. Thank you, everyone.

Dr. Le: Thank you.

Marcia Horn: Thank you.

ASCO: Thank you, Dr. Aggarwal, Dr. Le, Dr. Velcheti, and Ms. Horn. Learn more about lung cancer at www.cancer.net/lung. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

In this podcast, Dr. Tian Zhang and Dr. Afreen Shariff discuss common and sometimes serious side effects caused by a type of immunotherapy called "immune checkpoint inhibitors." They also explain why it is important for people with cancer to track the side effects they experience and discuss them with their health care team.

Dr. Zhang is an associate professor of Internal Medicine at UT Southwestern Medical Center and is a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. She is also a Cancer.Net Specialty Editor.

Dr. Shariff is an endocrinologist and assistant professor of medicine at Duke University School of Medicine and the Associate Director for the Multi-Disciplinary Toxicity Program at the Center for Cancer Immunotherapy at Duke Cancer Institute.

Together Dr. Zhang and Dr. Shariff host a podcast called Checkpoint NOW discussing a multidisciplinary approach to managing side effects of immunotherapy. Learn more and listen at www.checkpointnow.org.

View full disclosures for Dr. Zhang and Dr. Shariff at Cancer.Net.

Dr. Zhang: Hi, everyone. Thank you for joining. My name is Tian Zhang, and I specialize in treating patients with kidney, bladder, and prostate cancers. I'm happy today to be joined by my wonderful colleague at Duke, Dr. Afreen Shariff.

Dr. Shariff: Hello, everyone. I'm Dr. Afreen Shariff, endocrinologist, assistant professor of medicine, and associate director at the Center of Cancer Immunotherapy at Duke Cancer Institute. We're happy to talk today on the podcast Cancer.Net about immune checkpoint inhibitors and associated side effects that many patients often are concerned about. Neither of us have any disclosures related to this podcast content.

Dr. Zhang: Thanks, Afreen. With the increase in use of immune checkpoint inhibitors for patients with cancer and the prevalence of side effects and toxicities, we thought it was important for patients to understand what side effects to monitor for and when to contact their doctors for further guidance and management. We thought we would put together this particular podcast to focus on side effect monitoring from a patient perspective.

Dr. Shariff: I agree. We have some side effects that can potentially be attributed to multiple toxicities, but there are others that can be pretty straightforward. These are times when referrals to subspecialists like myself are necessary. And at other times, the treating oncologist primarily manages toxicities. The more patients know, the better prepared they will be when starting on immune checkpoint inhibitors. Tian, let's get started. When you are introducing a new start for immune checkpoint inhibitors to a patient in your clinic, what is your overall advice?

Dr. Zhang: Afreen, I think it's so important for patients to understand the general scope of side effects to monitor for. These include rashes and diarrhea, which are more common and relatively straightforward to attribute, but also other nonspecific symptoms like fatigue. I start with an overview about common side effects of rash and diarrhea, discuss a little bit more about rare side effects of inflammation in the lungs or liver, and then talk about potential endocrine side effects. And we do that all when the patient's starting immune checkpoint inhibitors in my clinic.

Dr. Shariff: Oh, that's great, Tian. What should patients know about diarrhea?

Dr. Zhang: Sure. So diarrhea is reflective of inflammation in the colon, what we call colitis. And this can occur in mild form or in a more severe form and is 1 of the most common side effects of immune checkpoint inhibitors. Changes in stool caliber, particularly loose or watery stools, and also frequency per day should be quantified and noted. Diarrhea does not often have blood, but bloody stools are also possible and should be reported. If bowel movements while on checkpoint inhibitors increase to 2 to 3 times more per day above baseline, patients should start reporting these to their treating oncologists for further management.

Dr. Shariff: Well, I'm sure our audience and some of the patients on immune checkpoint inhibitors will find this very useful. Now, skin rashes are seen quite commonly as well. For patients being treated with immune checkpoint inhibitors, what would you like them to know about these rashes?

Dr. Zhang: Sure. Of course, skin rashes vary from mild to severe and treatment varies with the diagnosis. If patients notice blisters and pain, this can certainly be an emergency and needs to be evaluated further by their oncologist who may then refer them to a skin doctor for more treatment. Large patches of red rashes can also be concerning. In general, we start with topical steroids for mild rashes and then add on oral steroids if topical ones are not controlling the rash.

Afreen, we see fatigue so often in patients treated with immune checkpoint inhibitors. Can you share some insight into different side effects that can cause fatigue?

Dr. Shariff: Tian, this is a very important question and common concern expressed by many patients. Now, often it is difficult to identify the cause if fatigue occurs in isolation without any other symptoms. Now, fatigue can result from immunotherapy and from cancer itself. But what I want to emphasize is the difference between ongoing fatigue and profound fatigue, which is a severe version affecting everyday activity levels. When patients experience profound fatigue, it's important to know what other symptoms are present that can help with identifying a cause.

Dr. Zhang: Great. And what other symptoms should patients be aware of?

Dr. Shariff: Sometimes this occurs with headaches and vision changes, indicating a side effect causing inflammatory changes of the pituitary gland in the brain. If this is a concern, your oncologist will advise further testing and a referral to a hormone doctor like myself called an endocrinologist. Now, if fatigue occurs with rapid weight loss, increased heart rate, and tremors, these can be signs of an overactive thyroid called hyperthyroidism. Now, in contrast, fatigue with weight gain can indicate an underactive thyroid. Both of these thyroid-related side effects will require lab evaluation to confirm a diagnosis.

Dr. Zhang: Afreen, fatigue is so common and also a presenting symptom for diabetes, as well. Can you tell us more about this?

Dr. Shariff: Yes. Fatigue and weight loss are common in new-onset or worsening diabetes. With immune checkpoint inhibitors, you can see a rare side effect of insulin deficiency, which is called type 1 diabetes. It's a rare side effect and needs treatment right away. What makes the symptoms a little different is that this fatigue is seen with increased thirst and appetite and a high blood sugar, which helps with the diagnosis. Now, Tian, we also see fatigue with shortness of breath. Now, what side effects can cause this?

Dr. Zhang: When a patient comes in with shortness of breath, we're often thinking about heart and lung toxicities from immune checkpoint inhibitors. Measuring oxygen saturation helps. Sometimes patients who have inflammation in their lungs, what we call pneumonitis, will have decreased oxygenation levels. In the clinic, if patients report shortness of breath on exertion, we will also obtain EKGs, echocardiograms, and other labs to evaluate for heart dysfunction. And often, subspecialists will help us in managing lung and heart toxicities from immune checkpoint inhibitors.

Dr. Shariff: Excellent. Now, what other complications can we see in a patient treated with immune checkpoint inhibitors?

Dr. Zhang: Liver dysfunction is 1 that we haven't talked about yet, and liver dysfunction is often without symptoms. Oncologists will monitor liver function generally every few weeks when patients are treated with immune checkpoint inhibitors. An elevation from baseline will spark suspicion that the immunotherapy is responsible, or other drugs. And often we will involve a liver specialist. And if, due to the immune therapy, we'll often treat that with steroids.

Dr. Shariff: That's very helpful. Now, what about other toxicities like kidney toxicity and toxicities to the nervous system?

Dr. Zhang: Sure. Certainly, these are rare forms of toxicities, the ones that affect the kidneys or neurologic toxicities. But they can certainly happen. For kidney toxicities, we would monitor kidney function on labs and sometimes would need to involve a kidney specialist. These are often primarily treated with steroids. Neurologic toxicities are rare but can be disabling and dangerous if diagnosed late. So patients can experience symptoms ranging from mild, like numbness and tingling, to more severe symptoms of weakness and paralysis. These situations often involve the input of a neurologist.

Dr. Shariff: Thanks, Tian, for your insight on these rare side effects. Interestingly, some side effects may be picked up on labs while patients may not have any symptoms. This is why oncologists are often checking blood work with every treatment. And it's important to bring up symptoms when you do experience them while on treatment. While these side effects are concerning, it's important to have a conversation with your treating oncologist to weigh your risk for each of these side effects. Most importantly, remember that a majority of these less severe side effects are manageable and do not need interruption of immune checkpoint inhibitors. This is a general guidance, and it's important to always refer to your treating clinician.

Dr. Zhang: Thanks, Afreen. I hope this session helps bring awareness for symptom management and side effects management for patients on immune checkpoint inhibitors. For other information on specific toxicities, there are several resources. You can follow us on Twitter at CheckpointnowMD, check out our podcast, Checkpoint Now, on Apple Podcast or Spotify, or also go onto the Cancer.Net website with more information on disease-specific treatments and toxicities.

ASCO: Thank you Dr. Zhang and Dr. Shariff.

To learn more about immunotherapy and its potential side effects, please visit www.cancer.net/immunotherapy. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, Cancer.Net Associate Editors discuss new research in brain tumors and gastrointestinal cancers presented at the 2021 ASCO Annual Meeting, held virtually June 4-8.

First, Dr. Glenn Lesser will discuss new research in 2 types of brain tumors, craniopharyngioma and glioblastoma.

Dr. Lesser is the Louise McMichael Miracle Professor and Associate Chief in the section on Hematology and Oncology in the Department of Internal Medicine at Wake Forest University, and is the Director of Medical Neuro-Oncology at the Atrium Health Wake Forest Baptist Comprehensive Cancer Center. He is also the Cancer.Net Associate Editor for central nervous system tumors.

View Dr. Lesser's disclosures at Cancer.Net.

Dr. Lesser: Hello. My name is Glenn Lesser, and I'm a professor of medical oncology and the Director of Medical Neuro-oncology at the Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina. I'm also the editor of the brain tumor section for ASCO's Cancer.Net. And today, I would like to briefly discuss 2 clinically relevant research studies involving patients with brain tumors that were presented at this year's ASCO's Virtual Scientific Program. I have no disclosures or relationships relevant to the second abstract I'll be discussing today. But by way of full disclosure, I have enrolled patients and I'm a co-investigator on the first study I'll describe.

As an introduction to those listeners not familiar with the current treatment options for patients with brain tumors, it's important to remember that patients with primary tumors of the brain have not seen the recent rapid advances in effective treatment strategies that patients with other malignancies have experienced. Thus, those of us who treat these patients really actively await the research results, which are presented and highlighted annually in several of our key national meetings, including ASCO, or the American Society of Clinical Oncology, Annual Meeting, which was, again, held virtually this year in light of the pandemic. I have selected several abstracts whose results, I believe, have immediate clinical relevance and can be used to modify our current standard of care therapies for the subgroups studied.

First abstract of interest was the presentation by Dr. Brastianos, who is the principal investigator of the Alliance A071601 study, which is a phase II trial of BRAF/MEK inhibition in patients with a tumor called a newly diagnosed papillary craniopharyngioma. A craniopharyngioma's a very uncommon tumor that can occur in both adults and children. And it typically arises in the region of the optic chiasm, a very important structure related to vision, and the pituitary gland, which is responsible for the production of a variety of hormones or compounds which stimulate other glands in the body to produce key hormones. These tumors often have cystic and solid components. And, as they grow, they compress the optic chiasm and the pituitary gland to produce symptoms, including loss of bilateral peripheral vision. Standard therapy for these lesions has included 1 or more surgeries and treatment with radiation therapy, including both external beam radiation and stereotactic radiosurgery. 

Although these tumors are generally not felt to be malignant, their continued growth and compression of surrounding structures leads to significant morbidity and symptoms, which dramatically worsen the quality of life of patients who have them and which, rarely, can be fatal. In adults, the most common variant of these tumors is called a papillary craniopharyngioma. And Dr. Brastianos and others have previously shown that these papillary tumors almost always have a driver mutation known as a BRAF V600E mutation. Now, a driver mutation is a specific mutation in the DNA, the instruction manual of the tumor cells, that gives those cells a selective growth advantage and, thus, promotes the cancer's development and spread.

In contrast, passenger mutations are mutations that may be present in the cancer cells but don't directly promote their growth or survival. The tumors that contain these driver mutations have the potential to be selectively targeted and effectively controlled by drugs which have been developed against that particular characteristic mutation. So this study builds on earlier case reports showing fairly dramatic regressions of these tumors with the use of agents that have been developed to target the BRAF V600E mutation, which is a characteristic of the more common aggressive melanoma skin cancer.

Over the last decade, 3 sets of drugs have been developed and brought to market, which have great efficacy in killing cells with this specific mutation. These drugs include a BRAF inhibitor, which targets the BRAF gene, and a MEK inhibitor, which essentially blocks an escape mechanism that the tumor cells try to use when confronted by the BRAF inhibitor. This is the only example I know of in oncology where giving 2 drugs leads to actually fewer side effects than if only the BRAF inhibitor was given by itself. But this trial had 2 cohorts of patients, 1 where it involves 16 patients with newly diagnosed craniopharyngiomas and a second arm enrolled patients whose craniopharyngioma recurred after radiation plus or minus surgery. The drugs used in this trial were vemurafenib and cobimetinib. And the goal was to give patients at least 4 months of this oral combination therapy. Dr. Brastianos presented the results of the newly diagnosed cohort, or Cohort A, at this year's ASCO. Remarkably, 15 of the 16 treated patients, or 94% of those treated, had a volumetric response, meaning a significant shrinkage of the tumor based on a central, independent review of their brain MRI scans. In fact, the only patient who didn't respond only received 2 days of treatment before they had to stop the medications due to some drug-related toxicity. So not only did these patients respond, but the median reduction in their tumor size was about 91%. And, furthermore, these responses appeared to last a long time, with only 1 patient recurring at the time the data was analyzed for ASCO.

The estimated overall survival of the patients on Cohort A at 2 years was 100%, while their estimated progression-free survival at 2 years was 93%. Phenomenal results. These drugs do have a variety of side effects which can occur to someone commonly and may lead to drug discontinuation in as many as a third of patients, although not nearly that many discontinue these drugs due to toxicity on this particular trial. These results, I believe, really establish combination-drug therapy with BRAF and MEK inhibitors as an effective standard-of-care option for selected patients with these newly diagnosed papillary craniopharyngiomas that contain a BRAF mutation. We're anxiously awaiting both longer-term follow-up of this study to determine the durability of these responses as well as the presentation of the results of Cohort B, which treated patients with recurrent disease after radiation.

The second study I'd like to highlight was presented in the oral poster session by Dr. Domenech on behalf of her colleagues in the GEINO, the Spanish Neuro-oncology Cooperative Group Trial 14-01. She presented the long-term results of this prospective trial, which randomized patients with newly diagnosed glioblastoma to 6 cycles of adjuvant temozolomide versus continuing the temozolomide for up to 12 monthly cycles of therapy. But since the publication of Dr. Roger Stupp's landmark trial in the New England Journal of Medicine in 2005, the standard therapeutic approach around the world for patients with newly diagnosed glioblastoma has included concurrent radiation and temozolomide chemotherapy for about 6 weeks, so both given at the same time, followed by monthly adjuvant temozolomide for 6 to 12 months with the drug being given for 5 days in a row each month. We have learned much about the molecular subgroups of glioblastoma and the characteristic molecular findings that may predict a given patient's responsiveness to this therapy since this publication. To date, however, clinical trials have not convincingly determined whether the benefits seen by adding chemotherapy to radiation stem from the concurrent phase of therapy, the adjuvant or post-radiation phase of therapy, or the entirety of the concurrent followed by adjuvant temozolomide. Furthermore, although the initial pivotal study described only 6 months of adjuvant monthly temozolomide to patients, many practitioners have felt that, frankly, more is better, particularly with a well-tolerated drug like temozolomide. And many physicians routinely give up to 12, or even more, monthly cycles of the drug.

As a result, many clinical trials over the last 15 years have allowed investigators to treat to the duration of their choice. Those in favor of this approach believe that more anti-cancer therapy is better, while those who limit temozolomide to only 6 months cite the increased cost, the increased rate of side effects or toxicities, as well as the mutational stress that prolonged alkylating therapy might put on tumors, which can theoretically lead to a more resistant tumor at the time of recurrence.

GEINO 14-01, which enrolled 159 patients, is the only large, prospective attempt to randomize patients to 6 or 12 cycles of adjuvant temozolomide therapy. The presented findings clearly show that adding 6 cycles of temozolomide after the first 6 adjuvant cycles produced no additional benefit in overall survival. With a median follow-up of about 20 months, there was no difference in the percent of patients surviving at 2 years between the arms, nor was there a difference in the percent of long-term survivors defined as survival of at least 30 months from the diagnosis. Patients in the extended therapy arm did experience an increase in hematologic or blood count toxicities in addition to the added cost and additional doctor visits the extended treatment generated. The authors, somewhat respectfully, concluded that the results of this trial should be corroborated in a prospective phase III trial. However, it's unlikely that such a trial will ever be mounted. And these results are likely going to be the best data we have to guide our approach in the future. Although more data will be provided in the full publication of the results of this trial, the presented results indicate that in most patients with newly diagnosed glioblastoma, the standard of care should involve a maximum of 6 months of adjuvant temozolomide chemotherapy.

In conclusion, the investigative teams behind both of these studies I've just described are to be commended on their efforts, which provide guidance on how best to care for patients with craniopharyngiomas and newly diagnosed glioblastoma. These studies are also outstanding examples of why well-done clinical trials that carefully test and evaluate the beneficial effects, as well as the toxicities of new cancer treatments, are critical to our goal of optimizing the treatment of our patients with cancer. Thanks so much for listening today.

ASCO: Thank you Dr. Lesser.

Next, Dr. Jeffrey Meyerhardt will discuss new research in esophageal and colorectal cancer. Dr. Meyerhardt is the Douglas Gray Woodruff Chair in Colorectal Cancer Research, Clinical Director and Senior Physician at the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, Deputy Clinical Research Officer at the Dana-Farber Cancer Institute, and Professor of Medicine at Harvard Medical School. He is also the Cancer.Net Associate Editor for gastrointestinal cancers.

View Dr. Meyerhardt's disclosures at Cancer.Net.

Dr. Meyerhardt: My name is Jeffrey Meyerhardt. I'm a gastrointestinal oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts. I'm an Associate Editor of Cancer.Net, ASCO's patient information site. Today, I'm going to discuss research on gastrointestinal cancers that were presented at the 2021 ASCO Annual Meeting. I do not have any relationships to disclose related to these studies. I'm going to focus on some studies related to esophageal and gastric cancer as well as studies in colorectal cancer. For esophageal and gastric cancer, we saw a variety of studies for immunotherapy in different settings. I think some important background information in considering esophageal and gastric cancer is that there are similarities and differences between the 2 cancers. Esophageal cancers can be squamous cell or adenocarcinomas. Gastric cancers that'll be discussed here are adenocarcinomas. In between the esophagus and the stomach is the gastroesophageal junction, one of the cancers with increasing incidence overall. They are also typically adenocarcinomas. For non-metastatic disease, the location of disease is treated differently. But for metastatic disease, most standard chemotherapy trials lump all of these sites together and have mixed squamous cell carcinoma and adenocarcinoma of the esophagus together. However, with immunotherapy, there are differences emerging to rethink this concept. While there are challenges in finding reliable markers to determine efficacy of immunotherapy in all cancer types, 2 markers have emerged relevant to gastro and esophageal cancer, PD-L1, or the combined positive score, and tumor mutational burden, which signals immunogenicity of a cancer.

While there were a wealth of studies of immunotherapy, 1 study that was noteworthy at this year's ASCO was CheckMate 648. The CheckMate studies have focused on the PD-1 inhibitor nivolumab. Checkmate-648 was a randomized study comparing unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma, previously untreated, randomized to 1 of 3 treatments. Nivolumab with 2 standard chemotherapies, 5-FU and cisplatinum, versus nivolumab and ipilimumab, a no-chemotherapy, just-immunotherapy arm, or chemotherapy only with 5-FU and cisplatinum. Nivolumab and ipilimumab was superior to chemotherapy only alone for overall survival and progression-free survival, particularly in patients with PD-L1 scores greater than or equal to 1%. Of note, there are some patients that don't benefit early on, which has been seen in other studies comparing chemotherapy to immunotherapy. There was similar overall and progression-free survival for immunotherapy alone compared to nivolumab, 1 immunotherapy with chemotherapy. More immunotherapy-related toxicities were seen with the combined immunotherapy arm, but more GI toxicities were seen with nivolumab plus chemotherapy. Overall, this study provides a non-chemotherapy option for patients as initial therapy for esophageal squamous cell carcinoma.

Turning to colorectal cancers, there are 2 studies that I wanted to highlight. The first study was the DESTINY-CRC01 study. This was a phase II study of trastuzumab deruxtecan, T-DXd, which is an antibody-drug conjugate of humanized anti-HER2 antibody bound to a chemotherapy, a topoisomerase I inhibitor. A phase II study means all patients got the same drug. The study focused on a limited population of metastatic colorectal cancer patients who overexpressed a protein called HER2. As with other cancer types, it is important to have molecular testing of colorectal cancer that may determine certain treatment options for patients. The several molecular features in colorectal cancer that are proven most important in treatment decisions include microsatellite instability, a feature that predicts effectiveness of immunotherapy; KRAS and RAS mutations that the lack of efficacy of a class of drugs called epidermal growth factor inhibitors like cetuximab and panitumumab; BRAF, which has specific drugs that target this mutation; and HER2. HER2 overexpression was first targeted in breast cancer. And there are also overexpressing stomach cancers that benefit from HER2-directed therapy. Approximately 3 to 4 percent of metastatic colorectal cancers overexpressed HER2. The DESTINY trial focused on patients who had progressed on at least 2 prior lines of therapy. So a heavily-pretreated population, 45% of patients with significant overexpression had a response to therapy. And 83% had disease control with a median of greater than half a year.

Interestingly, the drug was meaningfully active in patients who had prior HER2-directed therapy. While the drug had some expected toxicities, 9% of patients also experienced something called interstitial lung disease, inflammation of the lungs, which would need to be monitored. However, this drug does show promise in the armamentarium of targeted therapies for metastatic colorectal cancer.

The last trial I wanted to focus on is FOCUS4. This trial compared maintenance therapy with capecitabine, an oral form of 5-FU, versus active monitoring for patients with metastatic colorectal cancer. This is a topic that I found so important over the years and have not received as much attention I think it deserves. Fortunately, there are multiple trials in this field. And I think it's important to highlight them when new ones result. The basic principle is that when treating colorectal cancer these days with combinations of different chemotherapies, it is not uncommon to have a patient experience good disease control for prolonged periods of time. Initially, trials for metastatic colorectal cancer decades ago just continued therapy for as long as the disease was controlled for undue toxicities. However, with more effective therapies, there also have been increasing cumulative toxicities that catch up with patients over time. And there has been interest in continuing and considering changing at some point from multiple combination regimens to either maintenance therapy, some people call "chemotherapy light," or giving a full holiday off therapy. And there have been multiple trials over the years that have looked at these strategies. What is clear from those trials is that patients don't do better just staying on combination therapy. However, maintenance therapy is still chemotherapy. And a key to understand, is that even necessary? Are patients compromising outcomes by taking periods off of treatment?

FOCUS4 was a trial in the U.K. that randomized patients with metastatic colorectal cancer whose disease was controlled after 16 weeks of first-line combination therapy. They received either capecitabine with a usual 2 weeks of pills followed by 1-week break--or active monitoring with scans every 8 weeks. While the time till this tumor grew was shorter fully off of chemotherapy, the overall survival was not different between the 2 arms. This lack of overall survival has proven out in other trials. It was recently seen in a meta-analysis published in the Journal of the American Medical Association of Oncology recently. Active monitoring may not be the best option for every patient. But I think it is an important discussion between patients and their oncologists to balance quality of life and continued disease control.

Thank you for listening to this brief summary of new research in gastrointestinal cancers from the 2021 ASCO Annual Meeting.

ASCO: Thank you, Dr. Meyerhardt. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today, we're going to be discussing how parents can talk with their children about a metastatic cancer diagnosis and their prognosis. The information discussed in this podcast is based on a study published in JCO Oncology Practice titled, "Talking with Children About Prognosis: The Decisions and Experiences of Mothers with Metastatic Cancer." Our guests today are Dr. Eliza Park and Dr. Paula Rauch. Dr. Park served as the lead author on the study, and Dr. Rauch served as a co-author on the study. Dr. Park is the deputy director for the UNC Lineberger Comprehensive Cancer Support Program at the University of North Carolina at Chapel Hill in Chapel Hill, North Carolina. Thanks for joining us today, Dr. Park.

Dr. Eliza Park: Thank you for having me.

Brielle Gregory Collins: Dr. Rauch is the director of the Marjorie E. Korff Parenting At a Challenging Time, or PACT, program at Massachusetts General Hospital in Boston, Massachusetts. She is also a member of the Cancer.Net Psychosocial Oncology Advisory Panel. Thanks for joining us today, Dr. Rauch.

Dr. Paula Rauch: My pleasure.

Brielle Gregory Collins: Before we begin, we should mention that Dr. Rauch and Dr. Park do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now, to begin, Dr. Rauch, what are some of the challenges or fears parents with metastatic cancer have in talking with their children about their illness?

Dr. Rauch: I think as parents themselves are adjusting to their own diagnosis, whether it's the parent who is living with the cancer or their co-parent, they are hoping to not burden their children, to not worry them too much, and at the same time, they want to be sure to include their children in this very important event that's happening in the life of the family, and that is a tough balance for any parent.

Brielle Gregory Collins: And I recognize that these conversations might be different for parents who don't have metastatic cancer. So what ways are these discussions different when parents have non-metastatic cancer?

Dr. Rauch: I think for me, the easiest way to talk about this is to think about how we encourage parents to talk with their children about cancer, and that varies depending on the age of the child. But 1 way that we often talk with parents that they may explain cancer to younger children is to talk about the fact that our bodies are made up of millions and millions and millions of teeny-weeny, little cells that are kind of like Legos, and that what cancer cells are, they're kind of like Legos that are mixed up and don't fit together right and can't do their jobs right. When someone has an early-stage cancer, the goal of treatment by their medical team is to be able to get rid of the cancer completely. The goal of treatment when someone has metastatic disease, when those mixed-up cells are in more than 1 place in someone's body and the treatment can't make them go away completely, the goal is to keep those mixed-up cancer cells as small as possible and in as few places as possible so they don't interfere with a person's healthy cells.

Brielle Gregory Collins: Okay, thank you for explaining that. And what do parents with metastatic cancer need to know before talking with their children about their illness?

Dr. Rauch: I think parents generally know their children well. And so part of what they are thinking about is, first off, what is communication like typically in their household, what's the developmental stage of their child, what's their child's understanding of things, and also importantly, what their child's temperament is. You could think about temperament in children as being a little bit like personality in adults, but temperament is a way of capturing that kids have a typical way of adjusting to or understanding changes in their lives and in events that happen at home. And so taking all those things into consideration, parents may want to share information at a particular time, maybe at the beginning of a weekend when they have time to process with their child. They may have a good sense of what their child's understanding is. An older child may know a lot about cancer, a younger child, almost nothing. So we really think about parents as the expert on their own children. We have a lot of experience with the kinds of words that you can use in talking to children, but it's always a partnership of parents knowing their children and what their usual way of communicating is and then adapting this particular set of information to that knowledge base.

Brielle Gregory Collins: Okay. And I want to talk a little bit about prognosis and what parents should know about talking with their children about their prognosis. So first of all, just getting into that topic, why is it important for parents with cancer to know what their prognosis is?

Dr. Rauch: Well, you can't really explain anything to your child that you don't understand well yourself. Many parents will tell us that they find themselves asking really important questions of their oncology team because their children ask them really good questions or because even if they're not quite ready to describe fully something to their child, it's kind of like they want a script in their back pocket that they can draw upon if questions come up. When we have a sense of how we want to answer something, then it's easier to present a calm presence to children and really then to help them to feel their questions really are welcome.

Brielle Gregory Collins: Thank you, Dr. Rauch. And Dr. Park, branching into the study, you've described several different approaches that parents can use when talking about their prognosis with their children. So can you summarize for us what those strategies are?

Dr. Park: So that's a good question, and I would say, in taking a step back, kind of the overarching kind of goal of the study is that we know that these conversations can be nuanced and that they can be challenging. So given that we know that there's multiple decisions and challenges related to this, kind of how are the ways that parents who are remarkably resilient, thoughtful, find ways to kind of thread this needle in a way that makes sense for them and their families? And I think 1 of the main takeaways is to think about it is almost as, "What does honesty mean kind of when talking about cancer?" Because what can be an honest conversation in 1 family can look dramatically different from another's, and that's not to say that either way is better or worse, just different. So for some families, that meant discussing details about what their scans looked like and what that meant for their treatment and for the stage of their cancer, and for other people, it meant bringing up the possibility that their illness was chronic or may not be curable. And what we found is that for most parents, it was less about whether they should say something at all but rather a timing of when, and that takes a variety of decisions related to the factors that Dr. Rauch mentioned earlier.

Brielle Gregory Collins: I know in the study, there were several strategies that were outlined, so I want to go back to that for a minute. Do you mind just walking through what each of those strategies individually was and what they mean for parents who might be talking about this with their children?

Dr. Park: Absolutely. So as I mentioned before, there was many different strategies. So what I'm going to describe may not reflect everyone's experience, but the main 1 that we identified is parents simply wanted to be honest, and what that meant in terms of discussing their prognosis then took a variety of different forms. And so the strategies that came up most frequently that parents described using was, 1, kind of introducing the language of illness that might not get better in a way that can be fairly gentle. And so the language that many parents used was kind of, "Treatment for the rest of my life," and this was a way of signaling some of the changes that are going to be happening in their family moving forward but not necessarily including other statements that the children may not necessarily-- or the parents may not necessarily be ready to discuss right then and there.

The other common strategy that parents, I think, very instinctively used was having these many conversations over time. I think that the truth is this is not a 1 and done, to use a basketball analogy, conversation. This is something that happens kind of over the dinner table, at bedtime, in car rides, over the course of weeks, months, or most commonly, years, and there are a lot of children who grow up with a parent with cancer, and over time, the details can kind of emerge.

The third major way that parents would often approach these conversations was via questions, and the truth is that these conversations about prognosis were not always initiated by the parent. We had children as young as 4 who were asking questions about kind of what this means and what might happen next. And so parents often kind of look to their children's questions as kind of cues for cues of what they believe their child may be ready for in terms of specifics.

And I would say that the kind of last strategy is something that is just instinctual that I think every parent does without even thinking about it, which is just really reinforcing their love and their desire to help reassure their children that this may be information or news that is not desired but that they want the best for their children and to help their children feel secure, and I think that was probably the message that emerged in almost every description of parents' conversations with their children.

Brielle Gregory Collins: Thank you. And in the study, the most common barrier to having these discussions was that the parent didn't know what to expect in the future. So can you tell us a little bit more about that?

Dr. Park: Yes. So this was something that I think can be overlooked when we think about just, "What are the challenges in having these conversations?" I think we all understand that it can be emotionally taxing for parent or child, depending on what is happening with the illness, but this uncertainty about what happens in the future, I think, is a reflection of just how much progress has occurred in cancer therapies over the past decade. Many of our participants in the study had breast cancer, and these days, women can live with metastatic breast cancer for a decade or longer, and other individuals may not have quite the same expectation. And so because it can be so hard for patients as well as their providers to kind of be able to predict what happens next, it can be really challenging to figure out, "What does my child need to know next or even right now?"

Brielle Gregory Collins: Thank you for outlining all that. That's very helpful. And Dr. Rauch, is there anything that all parents should do when having these conversations about their prognosis with their children?

Dr. Rauch: I think most parents may not even think about this quite as prognosis but really more about what is going on with them. Just like any other family event, there is an illness that is underway within the parent, but there are also all kinds of changes in their home and things that will directly affect the child. So first, I think it's important to name the cancer because if you name it, then it can be talked about. If it's left as a euphemism, a bump, a lump, a boo-boo, that can be confusing. So I think the very beginning, even for children as young as 3, is to name it so it becomes something that is - I use a made-up word myself - talkaboutable so that there's the possibility and really the welcoming of questions in conversation. So I would say that's the first part.

And then, I think, a combination of what the goals are of treatment for the parent and also, what the impact is day to day, week to week, month to month for the child. And the amount of time that a child is thinking, and maybe it is really moment to moment for a preschooler, it may be a much longer amount of time for an older child. So thinking in terms of those bits of time that makes sense at different ages and then, I think, recognizing that children who are even 7 years old and older are not just getting their information from their parents, but they're getting information from lots of other places. Kids of all ages may overhear information at home, and that's the most confusing way to get clear information about cancer and about how the cancer is unfolding for the parent. So continuing to check in with kids, "What have you heard? What are you wondering about?" And certainly, for older kids, addressing the challenges of children getting information from the internet as opposed to directly from a parent.

Brielle Gregory Collins: Got it. So you definitely don't want it to be this elephant in the room. You want it to be an open discussion, and you want to be available to address the questions that your child might have and, of course, mitigate any fears that they might come across when they go on Google or talk with other people, things like that.

Dr. Rauch: Yeah, you want to give the message, "Don't worry alone." And I'll sometimes say to parents of adolescents, "Let your teenager know that you're going to either worry about them or worry with them." And if the teenager shares their concerns of what they're hearing, then the parent and the teenager can problem-solve together. If the child or teen doesn't share their information, then the parent's going to worry about them, and when a parent worries about instead of with their teenager, the parent is much more likely to be off the mark and frankly, more annoying to teenagers, and many teenagers will respond with a smile to that, "Oh, yeah. If you're guessing what's on my mind, you're going to annoy me more. If we can talk about it together, we can actually address the things that are front and center." And I think helping teenagers to recognize that what they read about on the web is about a large group of people and it's about the past. So it's neither about how things are going to be for the individual, their parent, nor is it representative of the future of cancer care. So the best guess about a parent's illness trajectory is going to come from talking with the parent and the parent talking with their medical team, and that's an important message to deliver to kids really in older elementary school age, middle school, and adolescents.

Brielle Gregory Collins: Definitely. That's helpful to know. And for parents who might be struggling with a child who doesn't want to talk about the illness, what advice do you have for people in that position if their children don't want to talk about it?

Dr. Rauch: So I think parents need to give updates to their child and say, "I want to be sure that you have the opportunity to hear, and I want you to hear from me. You might overhear me talking to your aunt about this or your grandparent or about that. So here's what's going on." Because, again, overhearing information is the worst way to have it communicated. It's not respectful to the child either to feel like, "Oh, my parent is talking to other people about the specifics of their illness and leaving me out." So communicating to a child, "I don't want you to worry alone. Here's what you might hear me talking about with others. Here's how my treatment or my illness may affect us at home and you, the child, in particular. I am eager to hear your questions, but it's up to you to let me know what's on your mind." And then I think for some kids, it's also giving them permission to talk to other caring adults, who are also a good source of information. Some kids can't bear to have the conversation with their parent because it's upsetting. They can see that their parent is upset or they feel upset themselves. But they might talk to their best friend's mom, or they might talk to another family member, or they might talk to a co-parent. And guiding children and teenagers to good resources, and by resources, I mean people who they can discuss the parent's cancer with, is also important.

Dr. Park: I would also add to that, as a clinician, I often ask patients, "What is helpful for you to know?" And what I might assume is helpful for them to know may be completely different than what is the truth, and we often find that that can be another way to help kind of open up some conversations to find out what are the kind of lingering questions or kind of unknowns in their child's mind.

Dr. Rauch: I also find that some teenagers who are not so eager to talk, if you ask them, "What's the dumbest thing anybody has said to you?", that sometimes is a gateway to a conversation.

Brielle Gregory Collins: That's a great question. And Dr. Park, going back to the study, many parents in the study were worried about upsetting their children by talking about their prognosis. So what can parents do to help if they're in this situation?

Dr. Park: Well, I think the truth is that parents are worried about upsetting their children because these conversations are hard for a good reason, and there is a need for balance and for weighing these different considerations. I think we find that parents can do things like kind of put their toe in the water. I don't think all this information needs to come out on the very first time they're telling their child about their diagnosis. If anything, we find that most parents take a more gradual approach. One of the things I often think about is that it takes time for adults to adjust to a cancer diagnosis and what that means. And similarly, it takes time for kids, too, and so there isn't necessarily a rush to kind of put it all out there on the very first conversation.

And the other things that I think that are helpful can be the more clear an individual is about kind of what they can expect with their illness and the different possibilities, I think, can at least reduce some of the uncertainty on the parent's end. It may not necessarily make the conversation less worrisome for the parent or the child in terms of that immediate moment, but I think oftentimes, parents can often then give additional information that they may not have known if they hadn't had more information from their provider about what the next treatment might be, if this 1 doesn't work the way we would like it to, or that things may not necessarily happen, things may not suddenly change on the drop of a dime tomorrow. I think that sometimes there can be uncertainty on the parent's end, and that is something that is very modifiable with having some conversations with their health care team.

Dr. Rauch: I think often parents can reassure their child that they're not expecting anything to happen this week or next week or this month or next month or today or tomorrow and that if things change, that they will update their child. And then the other thing I would just say is that parents are often very, very worried that when they share information with their child, their child will be so upset and sort of almost like that their childhood will stop at that moment. And in my experience, the vast majority of parents are surprised that their child accommodates as quickly as he or she does. It doesn't mean that it's not upsetting. It is upsetting, and actually, we would be worried if a child or a teenager wasn't upset by a parent's life-shortening cancer diagnosis. It is upsetting.

So using as the yardstick whether children are transiently or for a time upset is kind of the wrong yardstick. We would expect just lots of things upset kids, then they accommodate, and the parent is there to help them through that process. If parents wait too long to begin the conversation with their child, then they really have deprived their child or teenager of the opportunity to co-process this difficult news. Think about it like an elevator if you're starting at the penthouse, and you're going down a floor at a time. It's a lot easier to adjust to a gradual stepwise change than it is to go from the penthouse to the basement in free fall. So slowly having multiple conversations, as Dr. Park was discussing, but also not being afraid to let children be upset. Most parents have experienced their child's distress about a host of things. I've been watching my toddler grandchild start in daycare. He weeps when he starts in the morning, and then he's fine at the end of the day. I don't mean to minimize how different this challenge is, but part of what we do as parents and grandparents is to provide children with the opportunity to be safely upset with us.

Brielle Gregory Collins: Right. And I want to go back to this idea of the questions that children ask. I know we talked about the importance of addressing those questions. And Dr. Park, in the study, parents often relied on their children's questions to help guide these conversations, but are there any questions that parents should be asking their children when it comes to their illness?

Dr. Park: I think the truth is that we would like for parents to be listening even more than telling, and by that I mean that the main concern of parents, as Dr. Rauch mentioned earlier, is whether this is going to be too upsetting for their children, and that is not something that you can necessarily know or predict about how your child is kind of coping with this news by a single conversation or by you talking to them. Rather, I think it means kind of finding out kind of, "How does this impact their child's lives? What are the questions that they have been wondering about?" And really just, I think, being curious about how their child is thinking about this and what they understand, I would say, would be the kind of questions we would encourage all parents to think about. The other thing I also like to say is that children are remarkably curious people. I have young kids, and I think our dinner table conversations are essentially 1 long 20 questions pretty much every night, but not every child is necessarily going to feel comfortable asking some of these questions. And so having the parents at least find out what their children want to know, I think, can help put some of that expectation or pressure to ask these kind of bigger questions off their kids and perhaps kind of in the parent's hands.

Dr. Rauch: I have a couple of questions that I might suggest for parents of different ages. So I think parents of young children, whether it's the parent or a co-parent or someone else that asks to find out how young children understand why someone got cancer, it happens that sometimes in this early age where kids really feel like they caused the things that happen around them, they may have a misconception that they caused the parent's cancer or that when the parent is fatigued, that the fatigue is because the parent doesn't like them or is bored with them or irritable at them. So I think remembering that very young children are particularly self-centered, and that's developmentally normal to ask questions there. I think sometimes for older kids, just asking what someone who hasn't lived with a parent with cancer-- what other kids don't get about what it's like to be them can sometimes again be a way into having a child share what they feel isn't well understood by their peers or isn't well understood by the people around them.

Brielle Gregory Collins: Thank you for breaking those down. And thank you both so much for your time and for sharing your expertise today. It was so great having you.

Dr. Rauch: Thank you.

Dr. Park: Thank you.

Brielle Gregory Collins: For more information on this topic, please visit www.cancer.net/talkingwithchildren.

ASCO: If this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, 3 Cancer.Net Associate Editors discuss new research in cervical cancer, melanoma, and cancer in adults 65 and over, presented at the 2021 ASCO Annual Meeting, held virtually June 4th through 8th.

This episode has been adapted from the recording of a live Cancer.Net webinar, held August 9th, and led by Dr. Merry Jennifer Markham, Dr. Ryan Sullivan, and Dr. William Dale.

Dr. Markham is Chief of the Division of Hematology and Oncology and a clinical professor in the Department of Medicine at the University of Florida. She is also the Cancer.Net Associate Editor for Gynecologic Cancers. 

Dr. Sullivan is board certified in medical oncology and an attending physician in the Division of Hematology/Oncology at Massachusetts General Hospital. He is also the Cancer.Net Associate Editor for Melanoma and Skin Cancer. 

Dr. Dale is a clinical professor, the Arthur M. Coppola Family Chair in Supportive Care Medicine, and director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center. He is also the Cancer.Net Associate Editor for Geriatric Oncology. 

Full disclosures for Dr. Markham, Dr. Sullivan, and Dr. Dale are available at Cancer.Net.

Greg Guthrie: Good afternoon, everyone. I'm Greg Guthrie, and I'm a member of the Cancer.Net content team. And I'll be your host for today's Research Round Up webinar. This webinar will focus on gynecologic cancers, melanoma, and cancer in adults age 65 and older. Cancer.Net is the patient information website of the American Society of Clinical Oncology, also known as ASCO.

Our participants will be answering questions at the end of this webinar during the Q&A session. Please note that the participants cannot answer questions about anyone's personal medical situation. If you have specific questions about your cancer care, please contact a member of your health care team. Today we'll be addressing research from the 2021 ASCO Annual Meeting, which was held virtually in June, and our participants are members of the Cancer.Net Editorial Board. Now, they are Dr. Merry Jennifer Markham of the University of Florida Health. Dr. Markham is the Cancer.Net Associate Editor for gynecologic cancers. Dr. Ryan J. Sullivan of Massachusetts General Hospital Cancer Center, Harvard Medical School. Dr. Sullivan is the Cancer.Net Associate Editor for melanoma and skin cancer. Dr. William Dale of City of Hope Comprehensive Cancer Center. Dr. Dale is the Cancer.Net Associate Editor for geriatric oncology. And thank you, everyone, for joining us today. So starting us off today is Dr. Markham with highlights in gynecologic cancers.

Dr. Markham: Thank you so much, Greg. It's great to be here talking about a couple of studies that were presented at ASCO. Just to point out that I don't have any conflicts of interest for either of the 2 studies that I'll be presenting today. This first slide is a study that looked at a database to answer a question. And really, the primary question the study was trying to answer was whether HPV screening or cancer screening or HPV vaccination has made any difference in the United States over the last 15 years for HPV-associated cancers. And so the primary population that the results of this study really impact are any people, all people at risk for HPV-associated cancers, and these include oropharyngeal squamous cell carcinoma cancers. So head and neck cancers, anal and rectal squamous cell carcinomas, vulvar, vaginal, and cervical squamous cell carcinomas, and penile as well. So this study evaluated data from 2001 to 2017 in a database, the U.S. Cancer Statistics Database, and specifically tried to answer these questions. And the findings were rather complex, broken down by men and women, and so I'll walk you through.

In women, the overall incidence of HPV-related cancers was 13.68 per 100,000. And so of those cases, 52% were cervical cancer. What the authors found is that over the last 16 years, the incidence of cervical cancer decreased at an annual percent change of 1.03%. So a decrease annually by a little over a percent. And the incidence of cervical cancer in 2017 was 7.12 per 100,000. Over that same timeframe, the incidence rates of other HPV-associated cancers in women increased significantly. So rather than decrease, they went in the opposite direction. And specifically oropharyngeal, head and neck cancer, increased by 0.77% annually, anal and rectal cancer increased by 2.75% annually, and vulvar squamous cell carcinoma increased by 1.27% annually. Specifically in women over age 80, the incidence of anal and rectal cancer approached that of cervical cancer. The incidence of cervical cancer in that age population was 6.95 per 100,000, which was a decrease of 2.9% annually. Anal and rectal cancer incidence in women over 80 was 6.36 per 100,000 or 1.23% increase annually. So the authors did a projection model and found that the incidence in women of anal and rectal cancer was expected to surpass that of cervical cancer by the year 2025 for every age group over age 55.

Now if we switch to men, the incidence of all HPV-related cancers was 11 per 100,000 in the year 2017 and 81% were head and neck cancers. Over the last 16 years, there was an increase in HPV-related cancers in men 2.36% per year, with the highest increase in head and neck cancers, 2.71%, and in anal and rectal squamous cell carcinomas, 1.71% annual increase. Those who were at highest risk of head and neck cancer, the squamous cell carcinoma that I'm referring to, were older men. They were ages 65 to 69 with an incidence rate of 36.5 per 100,000 and an annual increase of 4.24%. White men actually had the highest incidence. So white men ages 65 to 69 had the highest incidence of head and neck squamous cell carcinoma at 41.6 per 100,000.

So it's a lot of numbers, a lot of data. Boiled down, what this really means is that cervical cancer has been decreasing. All other HPV-related cancers have been increasing. Now, the decrease in cervical cancer incidence is likely a combination of factors. Primarily, we have regular screening for cervical cancer, and we have HPV vaccination. Now, the risk for other HPV-related cancers, such as head and neck and anal and rectal squamous cell carcinoma, does remain high and is increasing, unfortunately. These are not cancers with routine screening. And so the authors concluded, and I think this makes sense, that screening and vaccination efforts, specifically HPV vaccination efforts, might help to impact those rising cancer numbers and help to decrease those rising incidence rates. So that is study 1. Greg, are we ready to go to the next one?

Greg Guthrie: Yeah, we are.

Dr. Markham: So this is the OUTBACK study. This is adjuvant chemotherapy following chemoradiation. That's primary treatment for locally advanced cervical cancer compared to chemoradiation alone. This was a phase III randomized study. We refer to it as the OUTBACK study, which was its official name. And this study sort of hits at the opposite end of that HPV cancer-related spectrum. So we're out of the prevention and in sort of incidence arena now in a realm of treatment. So this study impacts women who had locally advanced cervical cancer and specifically those who were able to be treated for cancer with chemoradiation. And just to clarify, chemoradiation, when that term is used together usually means chemotherapy and radiation given at the same time. And the chemotherapy is usually designed to make the radiation work better. So standard practice, the standard treatment that oncologists give for locally advanced cervical cancer is chemotherapy with a medicine called cisplatin and radiation, and this together is again chemoradiation.

So the question the authors wanted to ask in this study was whether adding chemotherapy at the end of chemoradiation helped to improve survival outcomes. So the study compared 2 groups, 1 group of women - and this was randomized - received chemoradiation alone. And that's absolutely standard of care practice. The other group, the experimental group, received chemoradiation, which was standard, but an additional 4 cycles of chemotherapy with a platinum and a taxane chemotherapy agent. The primary endpoint was overall survival. The study took a little bit of time to accrue. It recruited from 2011 to 2017, and ultimately 919 women with locally advanced cervical cancer were eligible and were analyzed in this dataset. Of those, 456 were assigned to chemoradiation, and 463 were assigned to chemoradiation followed by the additional 4 cycles of chemotherapy. What the study found is that overall survival at 5 years was similar in both groups. So 71% for the standard treatment arm and 72% for the arm that received the 4 additional cycles of chemotherapy. In addition, the progression-free survival was similar at the 5-year mark. So 61% compared to 63%. I think important to note is that this is a negative study. So the 4 additional cycles did not make a difference for these women. However, 81% of the women who were assigned to the chemoradiation and the chemotherapy had grade 3 to 5 adverse events within a year of being randomized, compared to only 62% of women who received the chemoradiation alone. So more women who received that experimental arm had more toxicity, more adverse events.

As we like to do in any randomized study, the authors did evaluate both groups of women to make sure there were no differences, and there were no statistical differences inherent between those 2 groups, and patterns of their cancer recurrence were similar in both groups. So what does this mean for our patients? For women with locally advanced cervical cancer, what we know now based on this study is that the standard treatment really does remain chemotherapy with radiation concurrent, so given simultaneously, and that we actually don't get any improvement in survival by adding additional chemotherapy. We do get extra side effects and extra toxicity. But women do not have better outcomes with this regimen. And that's it for these 2 studies, Greg.

Greg Guthrie: Thanks, Dr. Markham. I was wondering if you could really quickly give a sense of scope for how much do grade 3 through grade 5 adverse events affect somebody's well-being, quality of life.

Dr. Markham: Yes, absolutely. So typically, a side effect on a clinical trial are graded from 1 to 5. 5 is the absolute worst. That typically is death from a treatment. Grade 1 is very mild side effects such that you as a patient, if you're being treated with that, that treatment course may not really have much in the way of side effects or symptoms. But once we get to grade 3 and 4, there is some consequence. So, for example, for someone with anemia, they might actually require hospitalization or a blood transfusion. So it's definitely not a mild side effect. These are what we would consider significant or severe.

Greg Guthrie: Thanks, Dr. Markham. Now we'll move on to Dr. Sullivan with highlights in melanoma.

Dr. Sullivan: Greg, thanks so much for the introduction. It's a pleasure to be here today, and I'd like to thank Cancer.Net for the opportunity to provide highlights in melanoma from the Annual Meeting at ASCO. So I thought what I would do is show a few pictures and then describe what these pictures mean. So, the first study that I'm going to talk about is actually not a new trial. This is probably the fifth or sixth time this trial has been presented at ASCO. It's the CheckMate 067 study, which is a trial. And if you look at the upper right, this is a randomized trial. So patients were randomized to receive in gray ipilimumab, which at the time of this study launch was the standard of care for patients with newly diagnosed, advanced or metastatic melanoma. Patients could have been randomized to nivolumab, which had been shown to be effective in the second line after ipilimumab and was being compared in the front line with ipilimumab. And then the third arm and that-- was sorry, that's in green. And then the third arm in orange is the combination of nivolumab and ipilimumab.

As I said, this trial has been presented many times, but this follow-up presentation was with 6 and a half years of following how patients did on the study. And I don't generally like to show survival curves, certainly not overall survival curves, but I want to show them in this scenario, because what we're seeing, if you look at the lower left, this is progression-free survival. These are patients who started therapy and then their disease hasn't-- when the curve sort of flattens out, that means that whatever that number is, that's probably the number of patients at least with 6 and a half years follow-up, who are likely to remain progression-free over time. We know with ipilimumab, which is the gray line, and it shows 7% of patients who started therapy remain without growth of their disease. We know that those patients, if you're alive and without evidence of disease progression at 5 years, you're probably alive and without disease progression at 10 years. And that may be true for the combination of nivolumab and ipilimumab and nivolumab, which are the green and orange lines. And what's important about that is this is probably the potential cure rate of these therapies. As you can see, the numbers at 60 months and the numbers at 78 months don't look a lot different. And I would anticipate that about 30% of patients treated with nivolumab, which is a PD-1 blocking drug, and more than that, maybe 33 or 34% of patients treated with the combination of nivolumab and ipilimumab, are cured of their melanoma, which was metastatic at the time of starting treatment. And that is really amazing, particularly because this is a disease before these drugs came around that generally led to the death of greater than 90% and closer to 95% of patients who developed it. And that leads me to the second curve, which is the lower right, which shows that at 6 and a half years of follow-up, almost half of the patients treated with ipilimumab and nivolumab are alive and again, compared to probably less than 5% in historical dataset. So this is without a doubt, the most remarkable data when thinking about how patients do with melanoma that's ever been shown, and that's why I wanted to show these pictures.

This sort of picture shows actually the number of patients who are alive and treatment-free. So one of the important concepts of oncology, and I think if patients are polled, generally speaking, they would like a therapy that works, they would like a therapy that's tolerable. And ideally, if that therapy makes your disease go away, they'd like a therapy they can stop. And so on the left where it says nivo-plus-ipi and "n equals 145," what it's saying is that 77% of patients who are alive in and were randomized to that regimen are treatment-free, meaning they never needed another therapy. For the nivolumab, that's 69% of the patients. And for ipilimumab, that's 43% of the patients. And so I think the other point that I wanted to make is that not only does this therapy lead to really remarkable outcomes, but it also leads to one of the key metrics that we want, which are control of disease and not needing to be on therapy.

So to summarize, this study was patients previously untreated with unresectable stage 3 or stage 4 melanoma. It's a 6 and a half year update. And it's a randomized trial of nearly 1,000 patients. This, again, is the longest follow-up data of any anti-PD-1 therapy, with or without an anti CTLA4 antibody like ipilimumab. A durable progression-free survival was seen in about a third of patients with a combination, about 30% of patients with single agent nivolumab, and less than 10% with single agent ipilimumab. And the durable overall survival is close to 50% with the combination, over 40% with single agent nivolumab, and just over 20% for ipilimumab. And then again, importantly, patients alive at this data cutoff, almost 80% with the combination remained off of therapy and never required subsequent therapy.

And then one other important point that was presented by the authors was that in patients who had complete or partial responses, about 80% of those who were treated with a combination, those complete or partial responses were maintained over this time. That was compared to almost 90% of the complete response to the nivolumab, but only a little more than 60% of the partial response with nivolumab were durable. And this is a question that as an oncologist caring for melanoma patients, I'm asked all the time by my patients who have a nice response to therapy, "How long's it going to last, Doc?" And the answer is, in the majority of patients, it seems to last at least 6 and a half years. And again, having additional follow-up data is really important to be able to answer these key questions. So what does this mean for patients? Say the data suggests that a significant minority of patients treated with either the combination of ipilimumab plus nivolumab or single agent nivolumab have durable benefit. I'm not sure if I said it, but it's important that I do say it, that I have been a paid and an unpaid consultant with Bristol Myers Squibb, who is the sponsor of this trial, since 2017.

That goes for this presentation as well. So another really critical presentation that was made at ASCO this year was the so-called RELATIVITY-047 study. So this, again, was a randomized trial. This randomized over 700 patients to either the combination of relatlimab plus nivolumab or to nivolumab by itself. Relatlimab is an anti-LAG-3 antibody. Nivolumab is in the anti-PD-1 monoclonal antibody. Anti-PD-1 antibodies have become the standard of care for a number of different cancers, either in combination or by itself. And they block a key way that the cancer's preventing the immune system from attacking it. Relatlimab is another drug in targeting another one of these important molecules that cancers can use to help prevent immune destruction. And so the idea here is that blocking 2 of these key proteins that the cancer cells may be using to help prevent their destruction by the immune system might be better than just blocking 1.

So this is the progression-free survival. So, again, the number, the percentage of patients over time whose disease hasn't grown since starting the therapy. And what was shown is that the combination was better than just nivolumab by itself at preventing growth of disease. And to say it another way, of preventing disease progression.

And this is busy, and it's not meant to be kind of seen, but essentially that where you see all of those little teal bubbles next to a dotted line, they're all to the left of that dotted line. And that generally means that the combination was better in a lot of different subgroups of patients based on sex, based on age, based on how functional the patients were when they went in, based on BRAF mutation status.

And importantly, they look to see whether or not this was true also for patients who had PD-L1 expression, which is an important, potentially predictive factor of nivolumab treatment, as well as LAG-3 expression, which again was the target of one of the drugs. And the hint here is that there seems to be benefit no matter whether the tumor expresses PD-L1 or not, and whether the tumor expresses LAG-3 or not.

So to summarize, this is another study looking at patients previously untreated, unresectable stage 3 or 4 melanoma, randomized 700 patients, over 700 patients to either a combination of a LAG-3 inhibitor, relatlimab, and a PD-1 inhibitor and nivolumab versus nivolumab by itself. The trial met its primary endpoint. The combination was well-tolerated, although there was some increased toxicity with the combination compared to the single agent. But it doesn't appear that the toxicity is significantly dose limiting, and the majority of patients were able to continue therapy and similarly to those who were treated with nivolumab. And then this subset analysis, it consistently favored the combination. So what does this mean for patients? Well, the data suggests that the combination of relatlimab and nivolumab may be a new standard of care in patients with advanced melanoma. However, there are caveats, including it's contingent on this combination being approved by regulatory authorities. And also important to note that there's no data yet to determine whether this combination would replace or be better than the combination of the ipilimumab and nivolumab, the combination that I talked about in that first presentation that I'm summarizing as part of the CheckMate 067 study. So we really don't know whether this will be replacing frontline therapy for all patients who have unresectable stage 3 or 4 melanoma or just a subset. But it does seem that this data is potentially revolutionary in terms of how we manage this disease.

And finally, I'm going to talk about a clinical trial of a product called lifileucel. This is a trial sponsored by a company called IOVANCE, and I served on a scientific advisory board for the company over a year ago. This is a trial that was looking at the benefit of something called TIL therapy. So TIL stands for tumor infiltrating lymphocytes. So in tumors, we often can identify immune cells that may just be hanging around and watching what's going on or actually may be there with bad intentions, meaning they got there because they can recognize the tumor and are trying to destroy it. And long ago, in the 1990s, a group at the National Cancer Institute began to develop ways of removing these tumor infiltrating lymphocytes, testing whether or not the lymphocytes could recognize a tumor and then would give them back to patients. The cells themselves are unmodified other than they come out, they're grown, expanded, and then given back to patients. The way this works is that a patient will have a tumor removed. So call it the harvest. The lymphocytes or TILs will be removed. They'll be expanded. They'll be tested to see if the TILs actually recognize the cancer. And then a patient will be hospitalized, given chemotherapy to basically prepare their body to receive the TILs. The TILs will be given. And then patients will receive something called interleukin-2, which is a growth factor for the T cells. And then patients remain in the hospital until their blood counts recover from the chemotherapy. And then that's it. That's the only therapy that's given as part of TIL therapy.

So this study was looking at cohort 2, which was patients who had previously been treated for melanoma with a PD-1 blocking drug and then received TILs because the PD-1 blocking drug wasn't working and they needed another therapy. In the bottom left is a curve called a waterfall plot. Down is good. The down can go to 100%, which means that all the tumors that were measurable went away. And in the majority of patients' tumors got smaller. And about 35 to 37% of patients actually had what we call partial response or a complete response. And those responses to the right is shown that they tended to be ongoing and that with a median follow-up of over 30 months, the majority of responders remained in response. So 1 concern is do these responses last, and the answer is they seem to.

So to summarize, this was a trial for patients who had unresectable stage 3 or stage 4 melanoma who were previously treated with an anti-PD-1 antibody. This was an update of a clinical trial for lifileucel. Sixty-six (66) patients were enrolled. The majority had received both ipilimumab and an anti-PD-1 antibody. This it says upfront toxicity. That's why patients are in the hospital. But once patients leave the hospital, there tends to be very few long-term toxicities. Over 35% of patients had a response, and the majority of those responses were maintained with nearly 3 years of follow-up. One additional thing that was presented is that patients who actually had the poorest prognosis factors going in, meaning their disease grew right away when they got immunotherapy before or they had what's called an elevated LDH, those patients actually seem to have the best responses, the best outcomes. So what does this mean? Well, lifileucel's been shown to be effective in a subset of patients with PD-1 resistant disease, the anti-PD-1 resistant disease. And this data suggests that patients with primary refractory disease, anti-PD-1 may benefit the most. And it remains to be seen whether or not this becomes a standard therapy. But if it does, this data supports its use in this setting. I'll stop there. Thanks, Greg.

Greg Guthrie: All right. Thank you, Dr. Sullivan. And now we'll turn to Dr. Dale, who's going to discuss highlights in geriatric oncology research.

Dr. Dale: Well, thank you so much, Greg. And thanks to my fellow panelists, to ASCO, and Cancer.Net for the chance to present this exciting new work in cancer and aging or cancer with older adults. I'm going to present 3 studies, 2 of which are related to each other in that they're both about cognitive loss with the treatment of cancers, and a second one about the pre-existing deficits, which also partners with the others. So I think a really nice, natural follow-up to my colleagues who talked about the risks of balancing toxicities and treatment effects, which is often highlighted for older adults.

So the first study by Schiaffino, et al. is identifying pre-existing dementia in older adults diagnosed with cancer through a national claims database. I'll mention up front that I am a mentor for Dr. Schiaffino, but not of this particular work, which was done independently with another group of providers and mentors. So this study was done in older adults with cancer who were found to have pre-existing dementia of the Alzheimer's type or a related kind of dementia. So the advance of this case is to take a large database, not a clinical trial database, and through the development of a unique algorithm, actually, 2 of them, identify people who have perhaps unknown pre-existing dementia or cognitive impairment. These are all patients over 65 years old in Medicare, combined with a national cancer database called SEER, which is Surveillance, Epidemiology, and End Results study, for about a 10-year period. And it was conducted in people with 6 different kinds of common cancers. And what did we find that was new in this study? It's surprisingly common using this algorithm adapted from clinical diagnostics for people to have pre-existing cognitive impairment concerning for Alzheimer's or another dementia. This is often thought to be quite low, probably because most people with cognitive impairment do not end up enrolled in clinical trials. But if you look at a real-world database like this, 15 to 30% were found to have evidence of pre-existing cognitive losses. So they assessed the prevalence of this pre-existing disease through this algorithm across the cancer types, and it was even more common among certain racial and ethnic subgroups, basically non-white subgroups compared to white subgroups. Again, white individuals are more commonly enrolled to significant degrees in clinical trials.

So what does this mean for patients and caregivers if up to 1 in 3 older adults facing cancer treatment have pre-existing dementia, evidence of Alzheimer's, or related dementia? They need to be identified and screened for in advance of being treated for their cancer. Why is this important? Patients with cognitive impairment are at an increased risk for both overtreatment and undertreatment for their cancers. Those with pre-existing cognitive loss are at very high risk for a number of different toxicities and at high risk for mortality when being treated with chemotherapy and other kinds of cancer treatments. And if it's not identified in advance, they could be placed at higher risk and may want to reconsider the therapy choices. If someone is identified with dementia or cognitive impairment, one thing they're at especially high risk for, as we'll see in the next study, is chemotherapy-related, additional cognitive impairment during treatment, which can lead to a number of complications such as delirium and other problems. On the flip side, patients with dementia are often, as we saw with trials, not offered the most aggressive therapies, even when they're not at risk and offered the appropriate support. And so they're at risk of being undertreated based on perhaps an early kind of dementia that would be perfectly appropriate to be treated. So caregivers and family members may need to advocate on behalf of their older relatives or parents or grandparents to get appropriate treatment. So it's important to ask your oncologists and your primary care doctors about the risks when deciding what treatments and in some cases to undergo appropriate screening and testing for cognitive impairment prior to starting treatment.

So the next study is another study of cognitive impairment moving in the direction that the field of cancer and aging is moving, which is identifying effective interventions rather than simply identifying risk factors. So this is a phase II study of 2 combined interventions, exercise and low-dose ibuprofen for cancer-related cognitive impairment, essentially chemobrain, during chemotherapy for patients with cancer led by Dr. Janelsins and their team at the University of Rochester. Who does this study affect? Patients with cancer receiving chemotherapy who are facing cognitive difficulties with the initiation of chemotherapy and testing for 7 different domains of cognition, including memory, attention, concentration, and executive function, among a few others. This was 86 participants reporting cognitive difficulties during chemotherapy. The majority were breast cancer patients, and the vast majority were women. I do note that patients' average age was 54, younger than our usual cutoff of 65, but highlighting the fact that cognitive difficulties can be identified at any age with chemotherapy. I mentioned the 7 cognitive tests. Patients were then randomized into 3 different groups versus placebo for 6 weeks: an exercise alone arm, which included a walking program and a resistance band training program which has been validated in other contexts for cancer patients; daily ibuprofen, 200 milligrams given twice a day by itself; or a combination of exercise and low-dose ibuprofen together. And what did they find, particularly for the issue of attention? So this is the ability to maintain attention on a cognitive task. Exercise alone was the most valuable intervention. People were able to maintain their attention for a significant amount of time, over 20 seconds. Ibuprofen alone also improved significantly compared to placebo at about 10 or 11 seconds. Interestingly, the 2 together had a non-significant improvement in attention of about 8 seconds and raises some questions about why the 2 together would work less well than either alone, perhaps suggesting they use similar mechanisms. Self-reported cognitive function was also found in both of the exercise groups to be improved. So this was the subjective experience of chemobrain was seen to improve in those randomized to the exercise arms.

So what does this mean for patients with cancer receiving chemotherapy? These simple, validated, home-based exercises improved attention and the self-reported or subjective sense of cognitive performance. These are things that could easily be done in the home during chemotherapy and may well improve the situation for those who are experiencing chemobrain. Low-dose ibuprofen, just 200 milligrams, that's 1 over-the-counter pill twice a day, improves the same attention, although not quite as much as exercise. Again, the caveats are noted that these were younger patients. The benefits may be even greater for older patients who are more likely to have cognitive impairment, as we saw, and that it was primarily breast cancer patients and primarily women. There are still questions remaining about why the combination was less effective than either intervention alone.

And the last study I want to talk about is about other kinds of pre-existing conditions for older adults, focusing on those not with earlier stage disease, but with poor prognosis patients. So this was patients over 65 with poor prognosis cancers defined as a median survival expectation of less than 1 year and combined 2 large databases. To understand this, the Health and Retirement Survey, a large nationally representative study, combined with claims information or people's experience utilizing the health care system or on Medicare, and identified over 2,000 older adults with cancer, and just assessed the frequency of these pre-existing conditions, all of which are detected with a geriatric assessment, which is our standard way of assessing older patients with cancer and as part of the ASCO guidelines that were published a couple of years ago. 26% of the patients had lung cancer, 14% had GI cancer, and 60% had other kinds of cancers. What was found? Patients with poor prognosis have high rates of these pre-existing geriatric conditions. Of greatest concern, perhaps, is daily activities difficulties with well over 60% having difficulty climbing stairs, which are in the homes of many people, nearly 50% had trouble standing up from a chair, and a quarter had trouble walking 1 block. This is important as we anticipate giving people chemotherapy to know that the functional losses should be accounted for in advance, if at all possible, and to be prepared for people who may have lived in a house with stairs for many years or who have a low-slung chair that's difficult to get out of, that will become even more of a problem in the future. About a third of people over the year had a significant fall, 12% of which resulted in injuries, again, suggesting that changes in the home or a falls assessment be done or physical therapy to strengthen prior to treatments. And as we noted, just the last couple studies with cognitive impairment, nearly 1 in 10 had trouble managing their finances and another 6% had difficulties with their medications, highlighting additional challenges that come with older adults when they start on chemotherapies and helping anticipate problems that could be addressed or adjusted for. Of note, as people get older, these problems become even more pronounced. In those who are 85 and older who had cancer, over half had falls and even more presented cognitive problems with a fully one-fourth difficulty managing money, 12% difficulty taking their medications. Often, they're on a number of additional medications, just highlighting the challenges for simply getting through their days and anticipating that in the decision-making for starting on therapy or providing the appropriate support prior to starting on therapy. So I don't have conflicts of interest with this study or the prior study of any kind. And that's my last slide.

Oh, I'm sorry, I have 1 more. Let me do the "what this means for patients and families."  Advanced cancer is often accompanied by these geriatric conditions that affect health, functional status, cognitive status, falls, and social support is another common one along with the establishing appropriate goals of care. These conditions are detectable with the geriatric assessment. Here I've linked to the ASCO guidelines that came out in 2018. It's now becoming more of a standard of care for older patients. I will point out with the geriatric assessment, it does not require time in clinic to be conducted. It can be done in advance of clinic, and it can be done with nursing support or other staff doing it. Oftentimes online questionnaires can be answered so that these issues can be identified even prior to coming to the clinic or being seen in a video call. Interventions can improve many of these outcomes. We heard earlier from Dr. Markham about chemotherapy toxicities. Geriatric assessment interventions have been shown to decrease toxicities. Polypharmacies, so the reduction in the number of medications that are required that may not be appropriate any longer. Completion of advanced directives goes up with the use of geriatric assessment interventions, and the decision-making choices that need to be made for cancer therapies, whether it's chemotherapy or immunotherapy or others, are enhanced and happen more often with the geriatric assessment being done and help to mitigate the long-term outcomes, especially toxicities and geriatric issues that come up for older adults. I think with my last slide, my timing is just about perfect, Greg, so thanks.

Greg Guthrie: It is perfect, Dr. Dale. So thanks very much for that. And now we can move on to our Q&A session. And we can see what questions we have. Ah, so our first question is for Dr. Sullivan, and it is, is relatlimab a checkpoint inhibitor or is LAG-3 not a checkpoint?

Dr. Sullivan: Excellent question. LAG-3 is an immune checkpoint. Immune checkpoints are molecules that-- I guess the way to step back is to say that to have an active immune response, there needs to be a few things to happen. Typically what the immune response we're talking about against cancer is T-cell immune response. And so the T-cells need to be able to recognize something like a piece of tumor protein that's expressed on the outside of the tumor, like a flag. And then once they've sort of, there's this teaching process or priming process and then that process is involved. So there's a lot of these so-called checkpoints. Some of these checkpoints actually activate the immune system better, and some of these actually block the immune system from working well. And it's this delicate balance. It's almost like our immune systems have to be in the Goldilocks zone so it's not too hot, not too cold, but just right. And so a lot of these drugs, these checkpoint inhibitors, are blocking drugs to either activate cells or once the cells are activated and get into the immune microenvironment of the tumor, then they have to navigate these other potential checkpoints. And so PD-1 and PD-L1 are checkpoints on the immune system that are targeted by drugs like nivolumab, pembrolizumab, atezolizumab. And another checkpoint is LAG-3. So LAG-3 is expressed on what we call exhausted immune cells or T-cells. And so blocking LAG-3 can actually overcome that exhaustion and make those immune cells work better. So LAG-3 is a checkpoint and relatlimab is a checkpoint inhibitor. And that was a long way of saying it.

Greg Guthrie: One of the things that's really interesting about that study is that relatlimab is used in combination, and is that to reach that kind of Goldilocks situation that you were saying?

Dr. Sullivan: It's like the Goldilocks zone. Yeah, not too hot, not too cold.

Greg Guthrie: Just right.

Dr. Sullivan: Well, relatlimab and nivolumab are trying to make the immune system hotter. And so that's a good thing when we're talking about anticancer immunity. The downside, and to Dr. Markham's and Dr. Dale's points about toxicity, the downside of having the immune system too hot is that it can lead to side effects, and those side effects are generally inflammatory. So we worry the more checkpoints we inhibit, that the more side effects we'll see. So the combination in that first study of ipilimumab and nivolumab, when we use that combination, we get a lot of side effects that can be very challenging to get patients through that treatment, which is why we're looking for other combinations that will be more effective than just nivolumab or pembrolizumab by itself, but also will lead to substantial and better antitumor outcomes.

Greg Guthrie: Great. All right. We have another question, this one for Dr. Dale. How often do doctors evaluate patients for ADRD, or if they do not, will they still go ahead and provide chemotherapy?

Dr. Dale: Always risky for me to say what doctors do. I feel like I'm talking about my oncology colleagues like the anthropologist in Mars, I sometimes say where I'm just the geriatrician observing. So I don't know what people do for sure. We do know is that it's still not common for geriatric assessments that include cognitive screening tests to be done in oncology practices for a number of reasons. Resources is a particular challenge. So we already have very busy oncologists, particularly community oncologists, but all of them. And to fit in a cognitive screening test can be a real challenge. And so we have to come up with a different systematic way. Having said that, do they go ahead and treat? I think in most cases when people with dementia are identified, they are less likely to be treated for the concerns people have for cognition. But the way it's identified through family report in patients is known to be inconsistent and not as good as formal testing. So what I would say is we're getting better at creating screening tests that take very little time to do some cognitive assessment. And those who are screened as positive can then be sent for appropriate follow-up with a geriatrician or to a neurologist, whatever is appropriate. But those who are not can then move ahead with chemotherapy and not be excluded. So we're getting there, but there's more work to be done.

Greg Guthrie: Okay, great. And not a follow-up question, but another question for you, Dr. Dale. It seems like we've gotten a couple of questions about ibuprofen. So what is the mechanism by which ibuprofen is thought to improve or affect cognitive function in older adults with cancer?

Dr. Dale: Great. And I'm not an expert in the cognitive impairment directly, more in the health services sense, but my understanding is older adults are especially affected by inflammatory responses. So being frail, for example, is associated with inflammatory markers in our system such as CRPE and other inflammatory markers. And it's thought that ibuprofen as an anti-inflammatory reduces that. And those same markers are associated with this chemobrain cognitive impairment in several different studies. These are still association, so we can't say they're causal relationships. But the hypothesis is if we give ibuprofen and lower the inflammatory profile, that will allow cognition to improve and attention by extension. There is another theory I'll put out there. This is my personal one that I'm a little more sympathetic to, which is the inflammatory response from cancer and cancer treatments is fatigue. And fatigue is by far the most common side effect as Dr. Markham can tell us on the toxicity profile. It's very prevalent. For older adults, being fatigued affects cognition just like it does physical functioning. And it's very difficult to concentrate when you're so tired. And to the extent that we can reduce that inflammatory response and reduce the sense of fatigue, the more people could concentrate. Again, none of this is proven. This is still all at the hypothesis testing stage.

Greg Guthrie: Great. Our next question is for Dr. Markham. Is there any indication from the research that either vaccine, this HPV vaccine, or screening alone made the difference in the lowered incidence rate for cervical cancer? Or was it a combination of vaccination and screening?

Dr. Markham: So I don't think we know the answer to that really, and I have not seen it in studies. We have data that screening is helpful and we have data that the HPV vaccine is helpful.  So I suspect that it's the combination, but I don't know how much of each is contributing. I do think that like many things with cancer, it does take a multiple-pronged approach whether to treat it or to diagnose it. So to me, it makes sense that it's some combination of the 2.

Greg Guthrie: So a quick follow-up. For a lot of the squamous cell carcinomas that are included in that HPV study, they conclude by saying that there aren't a lot of screening protocols in place for these types of cancer. Do you think that we have the knowledge to do screening for those cancers and we just don't? Or will further research be needed to find ways to detect and prevent?

Dr. Markham: So I think like many of these things, we do need more research. The challenge with screening research is that we have to prove, our scientists have to prove that you can screen a lot of people safely and not in a costly   manner and actually reduce the incidence of cancer or some other outcome. And those studies are actually really hard to do, and they take a long time. I think the data that has come out on prostate cancer screening and on breast cancer screening with mammograms and at what age do we start and so on and so forth, I think is just a testament to how complicated the screening studies can be. So do we have the ability to screen? I think yes. I know that some dentists, for example, and head and neck doctors, head and neck specialists like ENT physicians, are able to just visually take a look in the mouth, for example, to screen for any abnormalities that look like cancer. Do we as a country or a health system have the ability to do that on a large scale [not] in a costly manner? I don't know the answer to that. And that's where we really do need more research. And same with anal and vulvar cancers, etc.

Greg Guthrie: That's great. Thanks, Dr. Markham. So I think we're going to move on to our final question, and that's for you, Dr. Sullivan, is how similar is TIL therapy to CAR T-cell therapy?

Dr. Sullivan: That's a great question. Both are T cells that are taken from a patient and given back to the same patient. But a CAR T-cell is made by removing a bunch of white blood cells from the blood and then those white blood cells, those T cells, are modified so that they are able to recognize the cancer. And when they do, the immune cell turns it on and they can actually expand. It's really like a living and modifying kind of in real time drug. And so there are a few of those CAR T cells that are approved by the FDA to treat a number of different diseases that express what we call an antigen that the CAR T recognizes. T-I-L therapy, or TIL therapy, are T cells that are removed from the tumor itself. They are not modified in the way, at least, that the standard NIH protocol, which is the protocol that we presented today and was presented at ASCO, which essentially is take the cells from the tumor, expand them, grow them, make sure they recognize the tumor, and then give them back. And so the difference is-- their similarities is they're both T cells and the T cells theoretically can recognize the cancer. The differences are that CAR T cells are taken from the blood and modified, and TILs are taken from tumors and are not modified.

Greg Guthrie: Great. That's very clear, Dr. Sullivan. Thank you, and thank you to all of our panelists for joining us today and sharing this great research and, of course, your expertise. It's been a real pleasure. And to all of you who attended this Research Round Up webinar, thank you to all of you for joining us today. You can find more coverage of the research from the ASCO Annual Meeting and other scientific meetings at the Cancer.Net blog. That's Cancer.Net/blog. If you're interested in more Cancer.Net content, please sign up for our monthly Inside Cancer.Net newsletter or follow us on social media. We're on Facebook, Twitter, and YouTube. And our handle is always @CancerDotNet with dot spelled out. Thank you for everybody for attending, and have a good day. Thanks.

ASCO: Thank you, Dr. Markham, Dr. Sullivan, and Dr. Dale. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, 3 Cancer.Net Associate Editors discuss new research in lung cancer, breast cancer, and sarcomas presented at the 2021 ASCO Annual Meeting, held virtually June 4-8.

First, Dr. Charu Aggarwal discusses new research on targeted therapy and immunotherapy to treat non-small cell lung cancer.

Dr. Aggarwal is a medical oncologist and Leslye M. Heisler Associate Professor for Lung Cancer in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine. She is also the Cancer.Net Associate Editor for Lung Cancer.

View Dr. Aggarwal's disclosures at Cancer.Net.

Dr. Charu Aggarwal: Hello, I'm Dr. Charu Aggarwal. I'm a thoracic medical oncologist, and I'm here to talk to you about research that was recently presented at the 2021 ASCO Annual Meeting. I will be discussing 3 studies of interest, and I should say that I do have a relevant disclosure to share. I have served as an adviser and consultant to AstraZeneca, which produces 1 of the compounds called durvalumab, for which I will be discussing research on. So let's start off with what was the most exciting or practice-changing research in thoracic oncology presented this year. We know that lung cancer as a field is changing quite fast and, in fact, is really becoming a poster child for application of targeted therapies. At this year's ASCO Annual Meeting, we heard about sotorasib, which is a first-in-class oral therapy that selectively and irreversibly targets the previously undruggable KRAS G12C mutant protein. KRAS G12C is an oncogene, or a molecular mutation, that occurs in patients with non-small cell lung cancer and accounts for about 13% of all patients with metastatic non-squamous non-small cell lung cancer. In a clinical trial called the CodeBreaK 100 phase 2 trial, patients with metastatic non-small cell lung cancer with this particular mutation in KRAS G12C were enrolled to receive sotorasib, which was administered orally at a dose of 960 milligrams once daily. Patients could have received previous chemotherapy or immunotherapy. And what we found was that out of the 124 patients that received therapy on this single-arm clinical trial, about 37.1% of the patients had objective clinical response, meaning that their tumors shrank when assessed by radiographic imaging.

Patients on this clinical trial had a median overall survival of about 12 and a half months, and patients were [responding] noticeably, with a response as early as 6 weeks, which was the time of the first assessment. Overall, this drug is very well-tolerated and, in fact, welcome news that the FDA approved use of this therapy for second-line and beyond treatment of patients that harbor a KRAS G12C mutation. So this is immediately practice-changing, it applies to a lot of our patients, and I think will serve as a really nice, immediate next therapeutic option in the second-line setting for our patients.

The next study that I want to talk about is the updated analysis of a trial called PACIFIC. We heard a 5-year update on this clinical trial at this year's annual ASCO meeting. For patients that have locally advanced non-small cell lung cancer, the current standard of care involves using combination chemotherapy and radiation, usually with a platinum-based chemotherapy for 6 to 7 weeks, followed by 1 year of immunotherapy with a drug called durvalumab. This standard of care has been based on a clinical trial called PACIFIC, which was first released in 2017, and then updated in 2018, showing a significant advantage to the use of this agent in the consolidation setting. At this year's meeting, we saw a 5-year update of the patients that were enrolled onto this large, phase 3 clinical trial. Patients were randomized to either receive 1 year of durvalumab or placebo following concurrent chemoradiation therapy for stage III non-small cell lung cancer.

At 5 years, we saw a consistent advantage in overall survival compared to placebo for patients that received durvalumab for 1 year following their definitive chemoradiation therapy. While these results are not immediately practice-changing, these are absolutely practice-affirming because looking at these curves at the 5-year time point really enable us to deliver the confidence to our patients that administering this 1 year of immunotherapy will help and improve overall survival and really improving the chances of cure following treatment for locally advanced, metastatic non-small cell lung cancer.

The last study that I would like to discuss is a study of adjuvant immunotherapy that is using immunotherapy after surgical resection for early-stage non-small cell lung cancer. While the study is not immediately practice-changing, I think this does represent a new paradigm. Currently, the standard of care in the post-surgical setting involves chemotherapy in case of involvement of lymph nodes and/or additional radiation therapy depending on which level of lymph nodes may be involved. This study, called the IMpower010 study, asked the question if immunotherapy in this setting following surgical resection and chemotherapy could provide a benefit. They looked at about 1,200 patients that were enrolled following surgical resection and had received 4 cycles of chemotherapy. Patients were then randomized to receive 1 year of immunotherapy with atezolizumab or best supportive care and were followed for survival.

At this year's meeting, we heard that patients who received atezolizumab, especially those patients that had stage II or IIIA non-small cell lung cancer, had a reduced chance of recurrence. Following the use of 1 year of atezolizumab, the chances of reduction in recurrence were about 34%, indicating that this is a positive study. I should add that atezolizumab for this indication has not been currently approved. Therefore, it is not practice-changing. However, I should also add that this is the first study of its kind to show an improvement in recurrence outcomes with the use of immunotherapy in the early-stage non-small cell lung cancer setting, making it a very notable study for this subgroup of patients.

Again, I think this has been a very exciting year for lung cancer research. And that wraps up our brief summary of new research in thoracic oncology from the 2021 ASCO Annual Meeting. Thank you for listening.

ASCO: Next, Dr. Norah Lynn Henry discusses two studies looking at new treatment options for early-stage breast cancer.

Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the Cancer.Net Associate Editor for Breast Cancer.

View Dr. Henry's disclosures at Cancer.Net.

Dr. Norah Lynn Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates in breast cancer from the 2021 Virtual ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. Today I'm going to focus primarily on treatment of non-metastatic breast cancer, especially that occurs in patients who have inherited mutations in BRCA1 or BRCA2. When these 2 genes have mutations or changes that decrease their function, it increases the risk of someone developing breast cancer as well as other cancers. But it also can give us clues as to which types of treatments these cancers may respond to. I'm also going to talk about a second study that was smaller, that looked at whether allowing patients to keep their ovarian function after chemotherapy is actually a safe thing to do.

One of the biggest stories from at the ASCO Annual Meeting was the results of the OlympiA trial. So in this trial, researchers studied a type of medication known as a PARP inhibitor, which is known to be effective for treating patients with metastatic breast cancer who have inherited mutations in those 2 genes I mentioned, BRCA1 and BRCA2. However, it was not known whether giving PARP inhibitors to patients with non-metastatic breast cancer would actually decrease the likelihood of their cancer returning. Therefore, in the OlympiA trial, researchers tried to answer this question. The OlympiA trial enrolled almost 2,000 patients who had inherited mutations in either BRCA1 or BRCA2. These patients had been diagnosed with either estrogen-positive or negative breast cancer, but HER2-negative breast cancer and were at high risk of having their cancer return. In this trial, patients were randomized like the flip of a coin to treatment with either the PARP inhibitor called olaparib or to a placebo for 1 year. Patients took the study medication in addition to their usual treatments. They had mostly all had chemotherapy already, and they took it at the same time as their anti-hormone therapy. After following patients for 3 years, the researchers found that the patients who got olaparib had more than a 40% decrease in the likelihood of their cancer coming back compared to those who got the placebo. The medication was pretty well tolerated. There was some nausea and vomiting, fatigue, and lowered blood counts, although there were some rare but serious side effects that can occur. So there are some concerns about using the medicine in everybody. The follow-up of the patients has been fairly short so far, only 3 years. So it is not yet known whether taking this medicine will enable patients to live longer after breast cancer. This is a medication that has already been approved by the FDA for treatment of patients with metastatic disease. And based on these data from the OlympiA trial, ASCO guidelines now recommend that olaparib should be considered as part of treatment for patients who have either a BRCA1 or a BRCA2 mutation and who have early-stage breast cancer who are at high risk of having their breast cancer recurrence.

So to switch gears a little bit, I'll talk about the other study I also found interesting. Often very young women who are diagnosed with breast cancer would like to become pregnant after they undergo treatment with chemotherapy. For these patients who want to become pregnant in the future, we often treat them with a medicine to block the function of their ovaries during chemo, sort of to put them to sleep with the hope that it will increase the likelihood that their ovaries will wake up and resume functioning again after chemotherapy is complete. However, we have worried that preserving the function of the ovaries might increase the risk of breast cancer returning, especially for women who have hormone receptor-positive breast cancer. This is because ovaries make estrogen, which is important for those types of cancers to survive. Investigators from Italy conducted a randomized study called PROMISE-GIM6 in which patients were treated either with standard chemotherapy or they got standard chemotherapy plus the ovary-blocking medicine. Now that they followed women on this study for more than 12 years after their diagnosis of breast cancer, they presented their final results. Importantly, they found there was no difference in the likelihood of cancer returning or in survival for patients who did or did not have their ovary function blocked during chemo. So these results should be very reassuring for patients who want to try to preserve their ovary function while they're getting treatment for their breast cancer.

Now, there were a lot of other research findings presented that were related to treatment for breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer. And we eagerly await the results of large, randomized trials so that the drugs that work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2021 Virtual ASCO Annual Meeting. Overall, we continue on a fast track with breast cancer with many new and exciting therapies being actively studied, as well as research helping support our patients to do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences.

ASCO: Thank you Dr. Henry.

Finally, Dr. Vicki Keedy discusses two studies in metastatic synovial sarcoma.

Dr. Keedy is an Associate Professor of Medicine in the Division of Hematology/Oncology and the Clinical Director of the Sarcoma Program at the Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center. She is also the Cancer.Net Associate Editor for Sarcoma.

View Dr. Keedy's disclosures at Cancer.Net.

Dr. Vicki Keedy: Hello, my name is Vicki Keedy, and I'm a medical oncologist at Vanderbilt University Medical Center, and I specialize in the treatment of patients with sarcomas. Today, I'm going to talk about 2 important studies discussed at the 2021 ASCO Annual Meeting. The first is the SPEARHEAD-1 trial, which is a phase 2 trial for patients with metastatic synovial sarcoma or myxoid/round cell liposarcoma. I'd like to note that my institution participated in and enrolled patients onto this trial, and I have participated as an advisor to this trial. The study evaluated an immunotherapy-based treatment called afami-cel, which targets the MAGE-A4 protein. This protein, also called an antigen, is commonly found in synovial sarcoma and myxoid/round cell liposarcoma cells. Afami-cel is called a T-cell receptor therapy, or a form of cellular immunotherapy. This therapy uses a patient's own immune cells called T cells and engineers them to be able to recognize and eliminate cells that express the MAGE-A4 protein. For this trial, patients could be between 16 and 75 years old but must have had 1 prior anthracycline, such as doxorubicin or ifosfamide-based chemotherapy. For this therapy to be effective, patients' cells must also have a specific group of markers called HLA-A02. HLA-A02 testing is performed on the patient's blood sample, while MAGE-A4 is tested on the patient's tumor tissue. Patients who are eligible for this treatment have their T cells collected through a blood draw called leukapheresis. Patients then receive a short course of chemotherapy, followed by infusion of the T cells. Patients receive no further chemotherapy unless the cancer were to progress. The majority of patients on this trial have synovial sarcoma.

The results show that 39% of patients had a partial response, meaning a decrease in tumor size by more than a third, and 2 patients had a complete response. While the number of responses is exciting, what is most exciting about these data is that these responses seem to last a long time despite the patients not receiving any further treatment for their cancer. Common side effects occurred to the chemotherapy portion of the regimen and were similar to what we would expect for chemotherapy. However, 1 particular side effect of interest for cellular therapies is called cytokine release syndrome. This occurs when inflammation occurs in response to the T-cell infusion. Patients can experience fever and flu-like symptoms or more serious illness. In this trial, 59% of patients experienced cytokine release syndrome, but only 1 patient had a more serious or grade-3 reaction. Patients must be re-monitored closely in the days and weeks following their infusion and are often hospitalized for part of this monitoring. A downside to this technology is that it requires both the correct HLA typing as well as tumor MAGE-A4 expression. In this trial population, only about 1 out of 3 patients were potentially eligible based on these 2 requirements. Having said that, the results of this trial suggest that T-cell receptor therapy against MAGE-A4 expressing synovial sarcoma and myxoid/round cell liposarcomas is a very exciting advancement for patients who are eligible for this type of treatment. Currently, this treatment is only available within a clinical trial, as it is not yet FDA approved.

Another important study reported this year were the results of catequentinib compared to dacarbazine in patients with metastatic synovial sarcoma. My institution also participated and enrolled patients on the study. Catequentinib is an oral therapy called a tyrosine kinase inhibitor. It blocks the signaling of multiple receptors that are responsible for tumor cell growth and invasion. Dacarbazine is a cytotoxic chemotherapy that is commonly used to treat patients with several types of sarcomas. To be eligible for this trial, patients must have had at least 1 prior anthracycline-containing regimen. Patients could've had a prior tyrosine kinase inhibitor, such as pazopanib, which is currently FDA approved for most sarcomas in the United States. This trial met its main endpoint of improving progression-free survival or, in other words, slowing down tumor growth, compared to dacarbazine. Although the improvement was relatively small, from 1.6 months with dacarbazine to 2.9 months with catequentinib, the data showed that there are a portion of patients who experience much longer benefit with nearly a quarter of patients still having stable disease at 1 year on the drug compared to 4% with dacarbazine. Side effects were as expected with this class of drugs, including diarrhea, fatigue, elevated liver enzymes, and high blood pressure. Catequentinib is not yet approved for use outside a clinical trial. And it is not known whether it is superior or equivalent to pazopanib, which is FDA approved for non-liposarcoma sarcomas.

These are only 2 examples of the interesting and important research being done to improve the treatment of patients with sarcoma. And while both happened to include patients with synovial sarcoma, the class of cancers known as sarcoma are actually 50 to 100 different cancers. Although it will not be possible to have a trial for every sarcoma subtype, through collaboration and patient education, we're able to research the individual sarcomas as the distinct entities that they are. Thus, it is important for patients with a metastatic sarcoma to go to centers that have trials for their specific disease when available. With this approach, we'll see even more advancements in the future for patients with sarcoma. Thank you very much for your time, and I hope I have more exciting findings to discuss in 2022.

ASCO: Thank you Dr. Keedy.  

You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today we're going to be talking about social determinants of health and how they can impact people with cancer. We'll cover economic stability, neighborhood, community, education, food access, and health systems. Our guest today is Dr. Karen Winkfield. Dr. Winkfield is a board-certified radiation oncologist and Ingram Professor of Cancer Research at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, and the executive director of the Meharry-Vanderbilt Alliance. She is also the Cancer.Net Associate Editor for Radiation Oncology and Health Equity. Thanks for joining us today, Dr. Winkfield.

Dr. Karen Winkfield: Thank you so much for having me, Brielle. I'm so excited for this podcast.

Brielle Gregory Collins: Yes, so are we. Before we begin, we should mention that Dr. Winkfield does not have any relationships to disclose related to this podcast, but you can find her full disclosure statements on Cancer.Net. Now, to get started, Dr. Winkfield, how would you define a social determinant of health?

Dr. Karen Winkfield: Yeah, it's such a big concept, right? The social determinants of health, the economic and social conditions that impact and influence the way that people, individuals, and groups actually experience their health status. And so 1 of the ways that I like to define it is simply the way that the CDC and others [do]. These are the conditions and the environments where people are born, where they live, learn, play, work, and age. And so it's an entire social context that people find themselves in that really can impact and influence their health and well-being.

Brielle Gregory Collins: Thank you so much for defining that. Now let's talk about some of the specific social determinants of health. So let's start with economic stability. What are some ways financial challenges can affect someone with cancer?

Dr. Karen Winkfield: Money is key, right? I always tell folks that wealth equals health, and certainly, health equals wealth as well. I mean, we certainly feel like, man, we are on top of the world when we're feeling well. But unfortunately, in our society, money oftentimes is 1 of the things that helps us drive well-being and health in this country. So just the simple thing we saw with COVID-19 when people lost their job, for instance. Many people also lost their health insurance. In this country, health insurance is tied to economics, right? But economic stability goes beyond just insurance. It's about what is the budget? Do you have a family budget? There is a recent study that suggested that about 21% of individuals in the United States do not have an emergency fund, right? So that means that if, for instance, they were just living and they were working on a budget, if something happened - their car breaks down; there's a flood in their hometown - they have no financial resources that actually are available to them to help them overcome that emergency.

And so economic stability is important. It's about where you work, if you are employed, what type of employment, are you a salaried employee, or do you only get paid the hours that you work? Which obviously has huge implications for cancer care, right? So if I am a cancer patient and I only get paid for the hours that I work, for instance, if I have a doctor's appointment that's at 10 o'clock in the morning and I have to maybe take 2 buses and a train to get there, or I have to drive 45 minutes, that's more than half the day that I am going to be there for a cancer visit or an appointment with a provider. And that means that I don't get paid for that, that nobody is covering that in terms of the finances. So it's really important to note that, yeah, it's about savings and things, but literally, the day-to-day, the employment that people have is really critical and the type of employment, what expenses people have. We know that cancer care is the number 1 cause of medical bankruptcy in the United States because a lot of the medicines are expensive. And so that economic piece is really critical to understand and for people to understand going into a cancer journey, number 1, where they are financially and what resources might be available to assist them throughout the course of their treatment.

Brielle Gregory Collins: That's helpful to note too in terms of there are places people can turn to, to help with these things. Let's move on to a person's neighborhood, which is another social determinant of health. So how can where a person lives affect their access to cancer care?

Dr. Karen Winkfield: Location, location, location, right? We think about that when we're buying a home, when we are thinking about if we have children, what school are they going to go to? It's about the neighborhood. It's about your ZIP code. And there are tons of evidence that suggests that your ZIP code matters more, frankly, than your DNA in terms of your outcomes, your health status. And so why that matters is you think about, "Well, how close am I to health care in general?" Right? And then you layer on cancer care. So, for instance, if I'm living in a neighborhood that is really close by my primary care team, that's great. But what happens if the cancer center, if I have a cancer diagnosis, is 45 minutes away or 10 miles down the road, but I have to, again, take 2 buses and a train, right? So your neighborhood determines what your access to a lot of things that impact health is going to be.

So it's not just about the health care facilities themselves, but you think about, "Is my neighborhood safe? Are there places that I can walk? Is my neighborhood walkable?" In the homebuyers' market, they'll actually have walkability scores. Is this a place-- where I'm living, is it easy to walk around? Because we know that health and well-being is certainly tied to exercise, the ability to go out and walk around, but to do so safely, right? If you're worried about whether or not there's going to be violence or if there's a lot of pollution or other things that impacting your ability to walk around your neighborhood, that's important. So geography matters because of proximity to health care, but it also matters with respect to proximity to other things that impact your health, including grocery stores, whether or not there are fresh fruits and vegetables that are nearby. These are all the components of health and well-being that are impacted by your physical neighborhood.

Brielle Gregory Collins: Okay. Got it. Thank you so much for explaining that. So community is another social determinant of health. And how does a person's community differ from their neighborhood?

Dr. Karen Winkfield: Wow, that is such a great question. And I had to think about my neighborhood that I lived in in Boston. Love, love, love that neighborhood, fabulous green kind of setting. I was 2 doors down from this amazing pond that I could walk around, so walkability plus, right? Not too far from stores, plus. It was beautiful. But you know what? I never felt part of the community. So neighborhood is the physical location, the geography, if you will, but community is about the people, who's around you, who's supporting you. And so one may actually live in a great neighborhood but not have community in that neighborhood. The community might be elsewhere. So maybe the community is their church family, right, or maybe their community are the families that they connect with that maybe their children are going to school with. So the community is, who are the people that you identify with, whereas neighborhood is the physical structure, if you will, of where a person lives and works.

Brielle Gregory Collins: Okay. Thank you so much for breaking that down. So community is basically a person's social group, the people that they spend time with. Okay. Got it. So how can community affect a person with cancer?

Dr. Karen Winkfield: Yeah. There are lots of influences related to community that people experience. And so the way that I think about a cancer journey is you have to think about the entire cancer continuum, meaning, are there ways to prevent cancer? Are there ways to get screening for cancer? What are the types of treatments that I need to be thoughtful of, right? Those are the entire cancer continuum, from prevention all the way through end-of-life care. That's the continuum. And so you can imagine that there are certain communities, that community influence, that may impact your risk for cancers. For instance, are you a smoker? Many people who are smokers actually smoke because maybe they had a family member who smoked, or their friends smoke, and so they smoke, or they may even just be social smokers, right? They only smoke when they're going out to a bar or after a meal with friends. That's how your community can impact your risk for cancer, because we know that tobacco use is the number 1 modifiable risk factor for cancer.

But here's another one that people don't think about, is obesity. Obesity actually is a very modifiable risk factor for cancer. People don't realize that being overweight or obese is actually a risk factor for cancer. So what happens if you're in a community where you guys like to go out and hike or you're very physically active? That's actually a prevention strategy. And so we know that community can impact one's risk for cancer, but what about the behaviors associated with cancer care? Well, I know that, for instance, in some communities, they don't like talking about the C word. They don't like talking about cancer. And so sometimes if you don't talk about things, you may not have the knowledge that you need to know how to protect yourself better, right, not only from reduction of risk for cancer but maybe also even, "Hey, there's screening that I can do. Let me make sure I get my mammogram," or, "Who am I talking to in my community?" Or, "Hey, you know what? I have a cancer diagnosis. Let me share that with my people, right, so they can learn from my experience." So community, the people that you connect with, the people that you identify with, your social context, that's important because there are ways that you can influence both positively and negatively one's outcomes related to cancer.

Brielle Gregory Collins: Okay. That makes a lot of sense. And we also want to talk about education, which is another really important social determinant of health. So how can a person's access to education have an impact on their cancer experience?

Dr. Karen Winkfield: Just like we were talking about neighborhood and location, I use that example of people moving into a particular neighborhood if they have children because they want to make sure the school systems are great, right? Why is that? Because we know that getting educated, having a good education-- even if it's just a high school education, having a good education opens doors, right? It opens opportunities. And similarly, having education status actually opens up doors related to health and well-being. So what's fascinating is we don't oftentimes think about how much of our health and well-being is tied into our ability to read, right? In our society nowadays, everything is text or is on online or you've got to Google it. You go to the doctor's office, and they hand you a stack of papers that's 5, 10 sheets long, and you have to fill it out. What happens if you can't read, right? So there are people in this country-- probably 20% to 25% of the United States is functionally illiterate. And so that impacts one's access to care and also can impact one's access to information around their care, around their health care, around their well-being. So information is key, and that oftentimes is related to our education level or our literacy because, unfortunately, there are some places in the United States that one could actually go all the way from kindergarten through high school and graduate and still not be literate. Sounds ridiculous, but that's what happens. And unfortunately, it's 1 of these things where this is why school districts and schools matter.

So the education is also related to language. And so as our community becomes more and more diverse - we have a lot more immigrant populations coming in - it's really important to think about language and how that impacts access to care. I was very surprised when I was the associate director of the Wake Forest Comprehensive Cancer Center that the number 2 most common language from an interpreter standpoint was Arabic. Who knew? In North Carolina. So Spanish was the first requested language, the top requested language from the interpreter services. But Arabic was number 2. And that was because we had a large number of Somalian refugees that were coming in who spoke Arabic as their primary language. So you can imagine being in a brand new-country, don't speak the language, and how do you even know how the country runs? Forget it if you have an issue that comes up where you need medical care. And that resonates for me because I remember I was on my honeymoon with my husband, and we were in Spain, and he got sick, and I didn't speak Spanish. And so we had to go to the emergency room not speaking that language. Language matters, and so that's why educational status matters. Whether or not you've had good early childhood education is key, what your literacy rate is, and certainly, having higher education oftentimes makes one more available-- and make themselves more available to the information that's out there on the web or other forms of printed materials that may actually impact one's ability to navigate the healthcare system better.

Brielle Gregory Collins: What about a person's access to food and how a lack of access to good nutrition can impact someone with cancer?

Dr. Karen Winkfield: Oh, Brielle, you are talking about something that has recently become more resonant for me. It was something I actually hadn't thought about, was this concept of food and food insecurity, until I heard a recent discussion at an annual conference that about 33% of individuals with cancer show up with some form of food insecurity. Now, what is food insecurity? Well, that may mean that you might not necessarily know where all 3 of your meals are coming from in the day, if you eat 3 meals a day, or it may be that you don't have fresh fruits and vegetables or access to that. Everything is canned because there's not a place where you can go and get fresh fruits and vegetables. There are places in this country that are considered food deserts, which means there might not even be a grocery store that's within a 10-mile radius, or even sometimes it's even much, much wider than that.

And food is important. Remember, we just talked about obesity being a modifiable risk factor for cancer. So what is the cause of the obesity epidemic that we're seeing in the country? It's not necessarily that people are overeating, although that's 1 thing. But we eat so much processed food, right? We eat so much stuff in cans that has sodium content out the wazoo, or we don't know where our food is coming from or how it's been engineered. And there may be things in the food that we don't control that may actually be causing some of the obesity epidemic. You think about how many calories are in some of the fast food products that are out there. You get a meal, for instance, a bundled meal. That meal can have 1,200, sometimes up to 2,000 calories that a person is consuming in a single meal. But you know why they're doing it? Because it's cheap. If I can go and I can eat for $4 for a meal versus having to kind of go and find food and cook it and all that kind of stuff, sometimes it's cheaper for people to eat food that's been heavily processed and that may have things that are low nutritional value, but it satisfies them. And so they're kind of forced, if you will, to eat that because they may be living in an actual food desert where they don't have access to fresh fruits and vegetables at a reasonable price. And so that's important. So from a prevention standpoint, thinking about food is critical, but so is not being hungry while you're going through cancer care, right? We need protein. We need nutrition to help our body repair. Cancer therapy is stressful, right? Cancer therapy impacts normal cells, and so we need to make sure patients have the access to the foods they need to help their body to recover during their cancer journey so that they can really not only just survive cancer but to survive it well during the process.

Brielle Gregory Collins: So it's not just about how much a person's eating. It's about what specifically they're eating and how what they're eating can help them through the cancer process.

Dr. Karen Winkfield: Absolutely.

Brielle Gregory Collins: Another social determinant of health is health systems. So what are some of the challenges health care systems can create for people with cancer?

Dr. Karen Winkfield:  Yeah. This is a very complex issue, right? So health care systems have grown and developed over the last couple of decades to become more and more complex. A lot of it is also driven by the insurance and by the payers, right, meaning what your insurance companies will cover, what Medicaid and Medicare will cover. This is a huge issue for patients because there's oftentimes lack of transparency, frankly, in terms of what insurance will cover related to cancer care along the entire continuum. So let me give you 1 example, for instance, of colorectal cancer. We know that the Task Force just recently reduced the age of colorectal cancer screening from 50 down to 45. And the reason why is there are more and more younger people who are showing up with colorectal cancer, and so important to make sure that we have a screening available to younger people. Well, that's all good and well, but what happens when you don't have availability of a doctor who can actually do a colonoscopy, right? So colonoscopy is the gold standard, if you will, for getting colorectal cancer screening. But there are other things, right? So this is where information is important. So people can get a stool-based card, right, where it's looking for DNA or looking for blood. And that test can be done as well. But there's so many different complexities that it oftentimes is a challenge for people to kind of think through what's going to work best for them.

Now, here's 1 of the things around the health care system in colorectal cancer that is a challenge for those of us who are in this space. So if a person goes for a colonoscopy and they're just going for a straight screening, it is covered by their insurance company, right? That screening is. Now, what a colonoscopy does, it takes a camera and looks inside the lining of the colon to see if there might be any polyps or any kind of abnormal growths that are inside the lining of the colon. So what happens if a doctor sees a polyp or something that's abnormal? Well, they go in, and they biopsy it or they remove it. What has just happened when the doctor does that, the provider does that, that has turned from a screening exam to now a diagnostic exam, and the insurance might not cover that. So what's the challenge is that you're going and you're encouraging people to go for screening, but the test itself is wonderful because, look, if a polyp was found and a doctor removes that polyp, that has just now prevented cancer. We know that for colorectal cancer, any polyp will eventually become a cancer, so you need to remove it, and that's why this colon screening is beautiful, because it's both screening and prevention. But our health care system is built in such a way that is complicated, where if you go in for a screening procedure and someone does a procedure that is potentially life-saving that now becomes diagnostic, it might not be covered. I mean, that's a complexity that most people aren't going to understand, and it's hard to explain.

So that's just 1 example of how health care systems are messed up with respect to insurance, but we also have to think about the individual institutions. How welcoming are institutions to individuals, right? Is it scary to walk into your cancer center? Is it overwhelming? How is your signage, right? Who's sitting at the front desk? Are the people who are welcoming people, do they look like the community that you're serving? These are all systems-based things that can be done or that can really complicate, if you will, cancer care if it's not done in the right way. And so these are just a few examples. Even we can talk about the fact that there are some cancer centers that don't accept Medicaid. I mean, what is that? That means you're excluding a whole host of individuals because they may have lower income than other people. Does that mean that people who have lower income are not as important as people with more money or have the ability to have private insurance? Shouldn't be that way. But again, health systems issues that can cause barriers and create issues-- especially when we talk about clinical trials, which are part of cancer care. We want people to be enrolled and participate in clinical trials because that's what changes the way that cancer care is delivered in this country. The reason why we are curing some breast cancers, the reason why we are curing other cancers is because there have been clinical trials that have led to discoveries that have allowed us to say, "Wow, this is a new standard of care. We're saving lives." But that means that if you don't have access to certain cancer centers where the clinical trials are happening, you are not able to participate. And so these are the barriers, the systemic barriers, the health system barriers, just a few of them that actually can really complicate care and make it such that individuals who might want to participate in treatments that can potentially change the face of cancer care-- they're not able to do it right now. So we have some work to do in trying to figure out how to open up the access and remove those barriers.

Brielle Gregory Collins: Right. Thank you so much for outlining that and for outlining all of these social determinants of health. So now that we've kind of talked through all of these different social determinants of health, how can addressing these social determinants of health help improve cancer outcomes?

Dr. Karen Winkfield: The biggest thing that we could do is prevent cancer. That's the way to have the best outcome, right? So if we are to think about location, where people live, their ZIP code as being a driver of health and health status, then that means that we need to start thinking about the context that people are living and saying, "What is it that can be done both from an individual, family, community, and a systems standpoint to help improve health status of different ZIP codes?" You may have seen the maps where people have mapped out a lifespan on a map based on a distance, right, whether it be along a highway or on the subway system, in Washington, DC, looking at the Metro system. And so there's people who are living, like, in the middle of DC, and they have a lifespan of 83 years. But literally, you go up on the yellow line, and you go up to northeast DC, and that drops by 10 years.

Where you live should not matter in terms of your health status, but it does. And so, again, by thinking about these social determinants of health, we can say, alright, what are the factors that are impacting access to care, that are impacting one's ability to prevent cancer or to reduce risk for cancers, meaning reduction of tobacco use, reduction of food insecurities, improving how you can walk around in a community or get exercise? What are people's employment status? Do people have to work 2 or 3 jobs just to make ends meet? If so, that means they're going to pay attention less to their health and well-being, right? Those are the sorts of things that we can think through to really help improve health status.

Now, the other thing that's really important in terms of thinking about from a cancer perspective is one's ability to get access to screening. So, again, social determinants of health, what insurance product do people have, making sure that people have access to the screenings. And like I said, this colorectal cancer example that I gave you is 1 where, what the heck, you go from screening to a diagnostic just because there's a procedure that's done that really can help prevent cancer. These are the sorts of things that are really vital to make sure that we're addressing. And also kind of thinking about, again, location, how do we get people to and from the places where cancer care is is really an important consideration as well because if people can't get to where the cancer care is happening, then obviously, they're not going to get access to the treatments that they need, or it may delay their care. And we know that delays in care can oftentimes lead to worse outcomes as well.

Brielle Gregory Collins: Right. Okay. And finally, where can people with cancer find resources to help them cope with the challenges of these social determinants of health?

Dr. Karen Winkfield: So anyone who has a cancer diagnosis is obviously thrust into this massive system, right? It doesn't matter if you're in a local community center where you might meet with a surgeon and then have to travel 30 minutes in the other direction to go and meet with a medical oncologist, and maybe you drive another 100 miles to go to radiation, right? There's that. Or you can go to a big giant cancer center where everything is put into 1 single building. You're popping up and down floors, or maybe everything's on the same floor. Doesn't matter what system you're in. My first recommendation would be let people know what your concerns are, right? Let 1 of your providers know, for instance, "Hey, listen, I'm struggling with transportation," or, "I'm worried about my job," or, "I'm worried about X." Really important to feel comfortable with your care team, right? So that first step in terms of overcoming barriers is, do I feel comfortable with the people who are helping me through this cancer journey? And it's the entire team, not just the doctor. It's the nurse. It's the therapist. It's the entire team that, hopefully, you feel comfortable with so you can say, "You know what? I just need to be open, and I need to share what my concerns are related to X," right? Doesn't matter if it's finances or food or whatever; just talk to your team.

And so 1 of the things that I'm trying to do is encourage providers also to ask people, right? So this is bidirectional. So, yes, we're talking right now directly to individuals who may experience cancer, or maybe the family member has experienced cancer. So, yes, please bring it up if you have concerns. But the other piece is providers need to do a better job asking kind of what people's concerns are as well. So that would be the first thing. Many centers will have social workers or other people who can help to navigate people through the system and be able to reduce some of those barriers. The other thing is I oftentimes will point people to wonderful resources online. So, again, not everyone has access to online kind of services. So this is why asking and having conversations with your care team is important because we don't want anyone to say, "Well, I don't have access to the internet," or, "I don't know how to Google," or, "I can't read." So please, please, please don't think that this is just comprehensive. I want to say please talk, right, opening your mouth and having conversations first, but certainly, online, there's some great resources. The American Cancer Society has wonderful resources. They've been providing a lot of transportation services for individuals with cancer for decades. I know that with COVID, some of that kind of was reduced, but it's a wonderful opportunity for volunteers even to say, "I'm going to give back. I want to be there to provide transportation services for individuals going through cancer journey." So the American Cancer Society has lots of resources.

The other thing is Cancer Support Community is another online venue. You can pick up the phone and call them. But Cancer Support Community is another opportunity to kind of really have-- these are some resources that are available. And I must say probably 1 of the number 1 resources I tell people to go to is Cancer.Net. And you know why? It's because they actually have a full-on resource page, right? So you can go to Cancer.Net and actually look at the resources page, and they list some of these, including Cancer Support Community, right? So there are lots of different resources that can be available to individuals. It's just a matter of looking, and it's a matter of kind of knowing where to go. So, again, I point people to Cancer.Net because it oftentimes has lots of different places that people can go to, some of which are related to a specific cancer diagnosis, right? So Komen for Breast Cancer is 1, but many of them generic, like the American Cancer Society or Livestrong or Cancer Support Community. So I just recommend people go to Cancer.Net or 1 of those other online resources to help them find what might work for them.

Brielle Gregory Collins: Thank you so much, Dr. Winkfield, especially for sharing your time and your expertise today. It was so great having you.

Dr. Karen Winkfield: Well, thank you, Brielle. I'm so grateful for this opportunity. I'm so thankful that we're able to talk a little bit about social determinants of health and things that people can do to help reduce some of those barriers to cancer care.

Brielle Gregory Collins: Yes, absolutely. And for our listeners, you can find more information on this topic at www.cancer.net/disparities.

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This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

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The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's podcast, 4 Cancer.Net Specialty Editors discuss new research in prostate, bladder, kidney, and testicular cancers presented at the 2021 Genitourinary Cancers Symposium, and 2021 ASCO Annual Meeting.

This episode has been adapted from the recording of a live Cancer.Net webinar, held June 16th, 2021, and led by Dr. Neeraj Agarwal, Dr. Tian Zhang, Dr. Petros Grivas, and Dr. Timothy Gilligan.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center.

Dr. Zhang is an associate professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Institute.

Full disclosures for Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan are available at Cancer.Net.

Greg Guthrie: So today, let's introduce our participants. First we have Dr. Neeraj Agarwal of Huntsman Cancer Institute and University of Utah and the Cancer.Net Specialty Editor for Prostate Cancer. Next we have Dr. Petros Grivas from Fred Hutchinson Cancer Research Center and University of Washington. He is the Specialty Editor for Cancer.Net for Bladder Cancer.

Next we have Dr. Tian Zhang of Duke Cancer Institute. And she's our Cancer.Net Specialty Editor for Kidney Cancer. And last, we have Dr. Timothy Gilligan. He is with the Cleveland Clinical Taussig Cancer Institute and the Specialty Editor for Testicular Cancer. So to start off, we'll have Dr. Agarwal talking about prostate cancer.

Dr. Agarwal: Thank you, Greg. It's such a privilege and honor to be here discussing these studies. So I would like to start with the first study, which was led by Dr. Stephen Freedland, a urologist at the Cedars-Sinai Medical Center in Los Angeles and was co-authored by me, Dr. Dan George, and many others. And here in this study, we present the utilization of therapies, which are associated and known to be associated with very significant, in fact, I would say dramatic improvement in overall survival, as shown by multiple randomized control trials over the period of the last 5 to 6 years. Just to take a step back for the audience, until 2014, standard treatment for metastatic castration-sensitive prostate cancer or newly diagnosed metastatic castration-sensitive prostate cancer used to be androgen deprivation therapy. And combining androgen deprivation therapy with those medications which were approved in the castration-resistant metastatic prostate cancer setting. So basically, using those drugs upfront led to dramatic improvement in overall survival with 33% to 35% reduction in risk of death across those clinical trials. So we actually wanted to look at the real-world utilization, so look at the real-world users of these medications in these patients who are being diagnosed with -- newly diagnosed metastatic prostate cancer in the United States. We also wanted to see how patients who belong to minority populations or racial minority populations, how they are being treated with these medications, which are backed by level 1 evidence. So this was a retrospective analysis of a Medicare database, more than 35,000 patients were included from 2009 to 2018. And we can see here a very representative patient population, predominantly white patients, 11.8% were African American, and 5% were Hispanic.

And here are the results. From 2010 to 2014, the use of standard androgen deprivation therapy with bicalutamide, was used in 97% of patients. We did not have trials reporting by that. Let's go to 2015 to 2016. Docetaxel was already approved in this setting now, and we can see some patients received docetaxel, but a small minority of patients received docetaxel. And then let's move to 2018, which is 4 or 5 years after docetaxel data had been presented by Dr. Sweeney in the ASCO plenary session. And abirateron was approved in 2017, and we are still seeing even like almost 2 years after -- we are still seeing the vast majority of patients being treated with standard androgen deprivation therapy or standard deprivation therapy with bicalutamide. So 62% plus 19%, we are talking about almost 80% of patients still not being treated with standard of care treatment, which is androgen deprivation therapy plus docetaxel, or androgen deprivation therapy plus abiraterone at this point of time, and now we have 2 more drugs available, which include enzalutamide and apalutamide in this study.

Another interesting thing was if you look at the patients who belong to minority populations, so let's look at African American patients compared to Caucasian patients. The use of intensified therapy was numerically lower. So in Caucasian patients, we are seeing higher use of intensified, as we call them, intensified therapy, or therapies which are considered standard of care, compared to African American men. So overall, the use was lower across the board, but if you look at African American men, the usage was even lower. So this is definitely concerning. I call it alarming, underutilization of life-prolonging therapy in patients who are being diagnosed with newly -- or new diagnosis of metastatic prostate cancer, and we definitely can improve this. We can definitely offer better care to our patients. It is not acceptable in my view to have 30% or less patients receiving standard of care therapies. So with that, I'll go to the next study.

 Greg Guthrie: Great, thanks. And this study is, "Health-related quality of life and patient-reported outcomes at final analysis of the TITAN study of apalutamide versus placebo in patients with metastatic castration-sensitive prostate cancer receiving androgen-deprivation therapy." And you were the presenting author of this, Dr. Agarwal?

Dr. Agarwal: Yes, Greg, thank you for giving the opportunity to present this study. And this is basically the continuation of the previous trial. I will not delve into in-depth analysis of these data. I just wanted to show that quality of life is not being impacted adversely by using intensified androgen deprivation therapy, so if you are using these drugs, which improves survival in a very significant fashion, and they are not being used in our patients, as we just saw in the previous study, what could be the reason? Is it the concerns about quality of life or adverse impact on quality of life? If that is the concern, this study, I think, helps refute those concerns. And in this study, which was a large study known as the TITAN trial, which led to approval of apalutamide for patients with hormone-sensitive or castration-sensitive metastatic prostate cancer and showed improved survival and radiographic progression-free and overall survival. We looked at quality of life data as reported by these patients, and these quality-of-life data were assessed by very standardized, validated scales known as FACT-P, or Functional Assessment of Cancer Therapy Prostate scale, or Brief Pain Inventory tool. And there are many other tools. So I will show you the results. And we can see here consistently there was no difference in quality of life as reported by the patients, or I would say any adverse impact on quality of life for these patients in any of these questions. As they were taking these questionnaires. So whether it was physical wellness, emotional wellness, functional well-being, social, or family, we go in and look at fatigue and there was no adverse impact on quality of life. At least from this perspective, we should not be concerned about using these drugs up front in our patients who have newly diagnosed metastatic prostate cancer.

 Greg Guthrie: Great. And so what does this mean for patients?

 Dr. Agarwal: From patient perspective, we can see here very clearly that using standardized tools, very validated tools, which have been used in multiple trials in the past, patients are not reporting any adverse impact on their quality of life when being treated with intensified androgen deprivation therapy. In this context, apalutamide.

Greg Guthrie: Great. Alright. So let's move on to our next study, which is, "Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer." The VISION trial.

Dr. Agarwal: Thank you. In my view, this is 1 of the most important studies presented in the 2021 ASCO Annual Meeting. This study was a phase 3 study where 7,000 patients were recruited, and they had metastatic castration-resistant prostate cancer and had disease progression on a prior novel hormonal therapy such as enzalutamide or abiraterone and the patients had received a taxane chemotherapy. So at least 1 taxane chemotherapy was required before the trial, and the patient had to have disease progression on a novel hormone therapy. These patients were randomized in 2 to 1 fashion to a novel drug, which is a type of radiation, intravenous radiation, as I would explain to my patients, and this is known as beta radiation. And this is a novel radiotherapy where radiation particle, which is delivering beta radiation particle to the cancer cells, is tagged to a molecule, which binds with the prostate cancer cells. So I'm simplifying it for the sake of our patients. And this particle or this compound was added to standard of care therapy and patients were randomized to standard of care therapy versus standard of care therapy plus this new compound. And standard of care therapy was a novel hormonal therapy or anything which did not include chemotherapy or radium 223, which is another type of radiation particle, but a different kind of particle known as alpha particle. So in this study, radiographic progression-free survival and overall survival were primary endpoints. We can see here that the study met both primary endpoints. There was a significant improvement in radiographic progression-free survival with an almost 5 month, 5.4 months, to be precise, improvement in radiographic progression-free survival, with a 60% reduction in risk of disease progression or death. If you look at overall survival, it was also improved in a significant fashion in patients who received the new compound known as lutetium-PSMA-617, and the median survival was improved by 4 months with an approximately 40% reduction in risk of death.  This was a well-tolerated drug overall, and if you look at hybrid side effects, treatment, and emergent side effects, there were 52.7% of patients in the experimental arm, and 38% in the control arm had those treatment-related side effects. So overall, Wwell-tolerated regimen with improved overall survival and radiographic progression. Thank you very much.

Greg Guthrie: Thank you, Dr. Agarwal. This is really interesting, and it will be interesting to see if this treatment does change standard of care based on this research. Let's move on to Dr. Grivas and bladder cancer research. Let's see, so Dr. Grivas, your first study is, "Avelumab first-line maintenance for advanced urothelial carcinoma: analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial." And Dr. Grivas was a co-principal investigator in this trial and is senior author of the New England Journal of Medicine publication and co-author of this abstract. Go ahead, Dr. Grivas.

 Dr. Grivas: Thank you so much, Greg, and thank you to Cancer.Net for the opportunity, and thanks to the audience. We welcome questions. I would like to update the audience today about the data we saw at the ASCO meeting, and I would like to place this data in context, and I would remind the audience the JAVELIN Bladder 100 trial that changed clinical practice was initially presented last year at the ASCO Virtual Meeting 2020 by Professor Powles. And this particular trial tried to answer the following question: does the immunotherapy, especially the PD-L1 inhibitor avelumab, add value in patients who completed chemotherapy in the first-line setting of metastatic urothelial cancer compared to just best supportive care in terms of longer life, in terms of overall survival, and time until the cancer grows or death, progression-free survival? This is important because until this study came about last year, the practice was, in the setting of spread metastatic urothelial cancer, when the chemotherapy stops, was we cannot give it for a long time because of potential side effects. Usually you used to wait until the cancer grows back, it progresses, or grows. So this trial compared this approach, the best supportive care, versus the immunotherapy with avelumab and the best supportive care. This particular trial, so the significant improvement of life expectancy and overall survival as well as progression-free survival, time until progression of the cancer or death, in the patients that received this immunotherapy drug avelumab as a way to maintain or sustain the benefit that is seen with chemotherapy. So we call this a maintenance therapy approach because we tried to maintain or sustain the benefit with chemotherapy. I want to highlight that this was published in the New England Journal of Medicine and the audience can retrieve that from PubMed if one wants to read the manuscript. The bottom line is this trial changed practice, and we can go now to updates. We saw this in this particular meeting, ASCO 2021, and I think the main question was, are there any particular subsets of patients, different categories of patients, who benefit more from the avelumab maintenance approach, or does this benefit all the patients? And we saw at the ASCO meeting, we saw that the benefit with this immunotherapy appears consistent across the board, across different subcategories of groups of patients. And I think that it's important to point out that we looked at patients who had what we call local disease around the bladder, that was invading this area, and the pelvic side wall that was not amenable to surgical rejection and also patients with spread of the cancer in distant sites, what we call metastasis. And we look at patients who had a primary origin in the bladder or higher up in the urinary tract, what we call kidney pelvis, or ureter, and we call this upper urinary tract, versus the lower tract, which is the bladder, and we also look at patients who had metastatic spread in the lymph nodes only or other parts of the body. And with the bottom line, we saw that the benefit with the immunotherapy was consistent across the different groups of patients. So many patients benefit from this treatment, again, with variable degrees, variable magnitude of benefit, but overall, the bottom line is, take home message is if you have clinical factors or other molecular factors, we do not have a reliable, accurate tool to select which patients should go with avelumab, so we offer it nowadays in every patient who has no contraindication to get immunotherapy and has received some disease control. Meaning a response of the cancer or stabilization of the cancer with the chemotherapy phase. So that has real clinical implications, and I encourage the audience to discuss with their oncologist about the optimal roles of immunotherapy with this maintenance setting after chemotherapy when this is controlled with chemotherapy.

Just for context here, I want to highlight the options the patients have in clinical practice. And when someone is diagnosed with spread urothelial cancer, they can be offered nowadays avelumab as a maintenance strategy to maintain the benefit of chemotherapy, and the other options include immunotherapy up front, like drugs like pembrolizumab or atezolizumab, and I will come back to that question how to select your treatment in my last slide. And I want to point out these are the options, and obviously clinical trials are always a great option for patients, and they should ask their oncologist about those options. So since I talked about immunotherapy, I want to point out that the ideal chemotherapy is cisplatin-based chemotherapy. Not everybody has enough fitness of the body to tolerate cisplatin. For those patients, we think cisplatin may be too much, we use carboplatin/gemcitabine, and we use avelumab maintenance in that scenario. What about immunotherapy after that? Is there data supporting that use? And the answer is yes. There is some data suggesting that immunotherapy can be an option for some of the patients, and in this particular slide, we update the data from another clinical trial. And I will let Greg, you can read the title of that.

Greg Guthrie: Sure, so this study is, "First-line pembrolizumab in cisplatin-ineligible patients with advanced urothelial cancers response and survival results up to 5 years from the KEYNOTE-052 phase 2 study." Dr. Grivas, you're a co-author on this study.

Dr. Grivas: That's right, thank you, Greg. This trial presented longer follow up to see what happened in patients who received the immune checkpoint inhibitor anti-PD called pembrolizumab because they were not fit enough to get cisplatin chemotherapy. Keep in mind this was designed before the previous study I showed you presented the results and included patients who were not fit for cisplatin, but some of them could have been fit for carboplatin. There was no comparison here, everybody received pembrolizumab as a single agent, alone, and in this particular study, we would try to see the degree of shrinkage of the cancer and the overall response rate as well as how long people lived over time. So with longer follow-up, by the way, we published this study in the Lancet Oncology years ago, and we have longer follow-up, and what you see here is a degree of shrinkage of the cancer, what we call overall response rate, was about 29% in what we call all comers, and it was higher size of tumor shrinkage in patients with high PD-L1 expression. PD-L1 is this brake of the immune system, the checkpoint of the immune system and highly expressive measured by particular assay that pembrolizumab works better in those patients. However, some patients even with low PD-L1 measured by this CPS score I put in the slide still might have benefits, so the take-home message here is there is a particular proportion of patients who can benefit from the checkpoint inhibitor pembrolizumab. PD-L1 can be used in that setting to help decide between chemotherapy and immunotherapy. However, we have not compared directly the chemotherapy followed by the available maintenance with immunotherapy up front, so this question is still lingering. However, if the patient has a response shrinkage to pembrolizumab, many of those patients may have a long-lasting response. We tried to figure out with research how can we predict who is going to benefit more from this treatment as a matter of ongoing research.

Greg Guthrie: Dr. Grivas, can you really quickly define CPS for our audience?

Dr. Grivas: Absolutely. Great question. CPS is a tool we use in the pathology labs to measure the PD-L1 expression. It can be measured by different assessing antibodies, and the pathologists use a score to define if the PD-L1 is high or low. In this particular study, CPS of 10 or higher defines PD-L1 high expression, CPS below 10 defines PD-L1 low expression, and this appears to have some association with a chance of the tumor shrinking with immunotherapy with pembrolizumab.

Greg Guthrie: Great. Thanks, Dr. Grivas. So our last study is, "Pembrolizumab versus investigator's choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer: 5-year follow-up from the phase 3 KEYNOTE-045 trial."

Dr. Grivas Very quickly, this study compared immunotherapy, pembrolizumab, the anti-PDL1, compared to chemotherapy with paclitaxel, docetaxel, or vinflunine, the latter one is in Europe, after progression of cancer growth on platinum-based chemotherapy. This was published in the New England Journal of Medicine a few years ago, and pembrolizumab prolonged survival, people lived longer compared to the chemotherapy. And this longer follow-up presented by Dr. Bellmunt and colleagues, showed the sustained results with follow-up, this population of patients had already received cisplatin-based chemotherapy and the cancer progressed, growth, despite that chemo, and in those patients, pembrolizumab appears to produce better results compared to this salvage chemotherapy shown in that slide. And this has implications because immunotherapy can be used in those patients after progression on platinum-based chemotherapy.

And just to wrap up here the discussion, I just want to give the options to the patients, see if someone has a new urothelial cancer, options include cisplatin/gemcitabine, or if someone is not fit enough for cisplatin, carboplatin/gemcitabine, and both of those scenarios can be followed by avelumab, and those with shrinking or stable disease, patients who have progression on platinum-based chemotherapy can get pembrolizumab and of course other options available. We can go into another podcast, and I encourage the audience to look and discuss with their oncologist about those options, and the take home message, the clinical trials is what got us here, and I recommend clinical trials to be discussed with your oncologist. Thank you so much, and I'll be happy to take questions.

 Greg Guthrie: Thanks, Dr. Grivas. So we're going to move on to Dr. Zhang, who is going to talk about kidney cancer. So our first study today is, "Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: a randomized, double-blind, phase III KEYNOTE-564 study."

Dr. Zhang: Thanks, Greg. I'm really excited to be here today and thanks, everyone, for joining. KEYNOTE-564 was presented at the ASCO plenary by our colleague Dr. Toni K. Choueiri, and this is a highly anticipated study in the adjuvant space for kidney cancer and enrolled patients with high-risk clear cell kidney cancer who had undergone either nephrectomy or a metastastectomy, removing their few sites of metastatic disease and treating those patients with either pembrolizumab for up to a year or placebo. And the endpoint was disease-free survival, and enough events had occurred by this ASCO for us to see the primary results. So the overall -- the study was positive. For the primary endpoint, disease-free survival improvement was met with a hazard ratio of 0.68 and the estimated disease-free survival rate at 2 years was 77% for patients treated with pembrolizumab versus 68% for patients treated with placebo. The overall survival favored pembrolizumab, but it was not yet statistically significant, and follow-up will be needed. Overall, we see an improvement in disease-free survival delaying time until recurrence for patients treated with pembrolizumab, and this was the first study in this adjuvant space showing checkpoint inhibition has a role in adjuvant treatment of renal cell carcinoma.

 Greg Guthrie: Thanks, Dr. Zhang. Our next study is, "Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: results from 42-month follow-up of KEYNOTE-426."

Dr. Zhang: This study, KEYNOTE-426, we are all very familiar with. Pembrolizumab and axitinib has been used for the last 2 years in the first-line treatment of clear cell metastatic kidney cell cancer, and it's a longer-term follow-up, more events and more understanding of what happens to these patients once they're treated in a longer term, so primary endpoints of course of this phase 3 study were progression-free survival and overall survival. When we're looking at this medium duration of follow-up at 42 months, so about 3 and a half years, pembrolizumab and axitinib improved both median overall survival as well as median progression-free survival. We'd point out that the -- at the 3 and a half year mark, the overall survival rate for patients treated with the combination was about 57.5%. And the progression-free survival rate was about 25%, so about a third of patients had not had progression of disease at 3 and a half years. Which is quite meaningful if they can stay on their first-line treatment for that long. The objective response was 60%, and of note, the complete response rate had been updated to about 10%. So there are some patients that do have delayed complete responses. And no new safety signals were observed. So overall, certainly still provides a lot of evidence to treat with pembrolizumab and axitinib for patients in the front-line setting.

Greg Guthrie: Great. And our last study here is, "Health-related quality of life analysis from the phase 3 CLEAR trial of lenvatinib plus pembrolizumab or everolimus versus sunitinib for patients with advanced renal cell carcinoma."

Dr. Zhang: This was the phase III trial in first-line treatment of metastatic clear cell kidney cancer that was reported at GU ASCO in February of 2020, and it was a 3-arm randomization to lenvatinib with everolimus in the standard study, and lenvatinib with pembrolizumab or sunitinib alone, and we saw the efficacy data in February, and here we're seeing the quality of life outcomes, and looking at how patients are doing, patient-reported outcomes on these treatments. And so with multiple quality of life measures, we're seeing improvements in patients that had better disease-related scores of symptoms when treated with lenvatinib and pembrolizumab versus sunitinib. We're seeing pain scores improve and patients having less diarrhea, appetite loss, when we're comparing against sunitinib. Of note, it's hard to specifically tie a particular symptom, if that's improved, because they've had better disease control or if it's more from the treatment side effect itself. So still hard to tease out a causality in these quality of life measures, but overall, improvement in patients' quality of life when treated with lenvatinib and pembrolizumab. And certainly provides some more data for patients receiving this combination.

And so I just wanted to highlight our ongoing phase 3 combination trials and first-line metastatic kidney cancer. PIVOT-09 with bempegaldesleukin has completed accrual in the first triplet of COSMIC-313 with ipilimumab, nivolumab and cabozantinib has completed accrual, so the actively enrolling studies currently are PEDIGREE and PROBE. These are studies that are being carried out in the cancer cooperative groups, as well as a triplet belzutifan lenvatinib with pembrolizumab, a study that Merck is running and all 3 very important studies we will continue to learn from and answer some important, clinically relevant sequencing treatment discontinuation, nephrectomy side effect questions. Thanks to everybody.

Greg Guthrie: We have 1 more. So, "Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer."

Dr. Zhang: Dr. Rodriguez from Spain presented this of papillary renal cell carcinoma treated with savolitinib and durvalumab, and specifically looked at the MET-driven subset of 14 patients out of these 42 patients. The efficacy primary end point was objective response rate. And of note, and median progression-free survival for the 42 patients who were all treated, it was 4.9 months and in MET-driven disease, so savolitinib targets MET, so MET-driven disease was 10.5 months and the median overall survival in everyone was 14 months, versus MET-driven was 27 months, and also higher response rates for patients with MET-driven disease. So I think personally, hypothesis generating, we will likely be seeing more trials with durvalumab and savolitinib in MET-driven papillary renal cell carcinoma.

Greg Guthrie: Thank you, again, Dr. Zhang. And Dr. Gilligan, we're going to talk about some testicular cancer research now, and the first study is, "Testicular cancer in the cisplatin era: causes of death and mortality rates in a population-based cohort."

Dr. Gilligan: So this study was looking at what happens with testicular cancer patients who are cured of their cancer, are they at risk of dying of other causes? They looked at over 5,000 men treated between 1980 and 2009, so it's important to recognize that some of the treatments given back then are a little different than the way they're given now. And it looked at the risk of death from causes other than testis cancer compared to men without testicular cancer in the general population, and the concerning finding from this study, and it's not the first study to report this, was that the risk of non-testicular cancer death, that is, death from other causes, was increased by about 28% in men who had been treated with radiation therapy and about 23% in men treated with chemotherapy. There's a risk of non-testicular cancer death, the risk, excuse me, was doubled in those whose treatment included both. So it was higher with either radiation or chemo and it was actually 100% higher or double than both those who had chemotherapy and radiation. As you got more chemotherapy, the risk went up. There was no trend towards the increase with just 1 or 2 cycles. We started to see the increase with 3 cycles, and it became statistically significant with 4 cycles. But there wasn't much difference between 3 and 4 in terms of the absolute number that was seen. In terms of death from other cancers, so why is this happening? Other cancers are a major issue after chemotherapy or radiation. Again, the risk was increased 60% after radiation therapy and 43% after chemotherapy, and those who got both, the risk of cancer was 3 times higher than the general population. So that's in men who had chemotherapy plus radiation therapy. Fortunately, there are not a lot of men who get both of those treatments anymore. Non-cancer deaths increased 17% after chemo and 55% of treatment included both. So the risk for non-cancer deaths was not as high as the risk for death from secondary malignancies. Interestingly, the risk of suicide increased 63% in men treated with chemotherapy. That's not affecting as many men as those other numbers, even though 63% number looks high, but it is a concern. Those treated only with surgery did not have an increased risk of non-testicular cancer death. What does this mean for patients? It really means when we can use surgical treatments instead of chemotherapy or radiation as an additional incentive to try do that, and what that may mean is there should be a larger role for retroperitoneal lymph node dissection as an alternative to chemotherapy or radiation therapy. Secondly, for patients getting chemotherapy, it's important to minimize the number of cycles of chemo as long as we're not sacrificing long-term cure rates, because the biggest risk of death is dying from the cancer, but that means limiting to the 3 cycles instead of 4 cycles is probably a good idea, and I think it's an argument to use 3 cycles of BPE instead of 4 cycles of EP because it's really the etoposide and the cisplatin that is linked to the secondary cancer risk, not the bleomycin, as far as we know. And then lastly, we need to pay attention to the mental health needs of men treated with chemotherapy. That there is more emotional distress and we're seeing here a higher risk of suicide.

 Greg Guthrie: So our second trial is the, "SEMS trial: result of a prospective multi-institutional phase 2 clinical trial of surgery in early metastatic seminoma."

Dr. Gilligan: So if we're going to use more retroperitoneal dissection and less chemotherapy or radiation, 1 place to do that is in stage 1 and stage 2 seminoma, and many centers around the country have started doing that, and this was a trial that looked at that approach. So these are men who normally would be treated with chemotherapy, 3 cycles of BEP, or radiation therapy to the back of the abdomen and part of the pelvis potentially. This study looked at the small number of patients, 55 men, low volume, stage 2 seminoma up to 3 centimeters of size and maximum dimension. And what they reported of those men undergoing retroperitoneal lymph node dissection, 10 relapsed, so 18% relapsed after median follow-up of 24 months, they were all alive at the end of the study. No deaths. 8 of 10 relapses were treated with chemotherapy, and 2 were treated with additional [surgery]. Out of the 55 men, 8 ended up getting chemotherapy. Normally, all of them would have gotten either chemo or radiation. Relapse-free survival was 87%, overall survival was 100%.

Seven (7) patients developed complications after RPLND and 5 of them were mild. Two (2) were more severe. So it's a well-tolerated treatment, if it's done at a large volume center, it's worth noting that the centers participating in the study were large volume centers. Again, if not treated with RPLND, all of these men would have gotten chemo or radiation. The relapse rate after chemotherapy or radiation is about 5%. So the relapse risk is higher after surgery, but in the sense, if we take 100 men with early stage 2 seminoma and do an RPLND instead of chemo or radiation, we can spare 80% of them the long-term effects of chemotherapy or radiation. Alternatively, if the priority is simply to prevent a relapse, radiation therapy and chemotherapy are more effective at that, the relapse risk being 5% but at the cost of long-term side effects from chemotherapy or radiation. Bottom line there is an additional treatment option for low volume stage 2 seminoma for men who prioritize avoiding the complications of chemotherapy or radiation therapy. Both of which are associated with an increased risk of death from other causes. The price we pay for that is the relapse risk is higher with RPLND compared to the other approaches. Not all centers are going to be offering this, but major centers that do a lot of testicular cancer, this is becoming a new treatment option. With the caveat that we have less experience with this approach. This is a relatively small study. And we have a lot more experience with chemotherapy or radiation. I don't think there's a one size fits all here, but I think patients should talk about it with their doctor. If they have early-stage seminoma, they should talk about surgery as an alternative to radiation or chemo.

Greg Guthrie: Here we go. "Surveillance after complete response in patients with metastatic non-seminomatous germ-cell tumor."

Dr. Gilligan: So this study is looking at the question, if you take a man who has retroperitoneal lymph nodes that are enlarged and metastatic non-seminomatous testis cancer with lymphadenopathy in the back of the abdomen and you put them through chemotherapy and at the end, all retroperitoneal nodes are now within normal limits, normal size nodes, and no bigger than 10 millimeters or 1 centimeter, do we need to do a retroperitoneal lymph node dissection on those patients? Some centers recommend it and some don't. This looked at 388 men in that situation. They were put on surveillance. These men did not undergo the post-chemo RPLND. Two years survival, overall survival was 97.8%. Two-year progression-free survival was at 90%, 34 patients relapsed, and 10 of the men died. Men who did relapse had surgery, chemotherapy, or both as subsequent treatment. There's a prior similar study that was multicenter that had longer follow-up of 5 years, and they reported of ;161 men who had a complete response to the first-line chemo, 10 relapsed (that's 6%) and none died. If we combine these 2 studies together, the bottom line is you would have to perform a post-chemotherapy retroperitoneal dissection, which is a big operation, on about 550 men to prevent potentially at most 44 relapses and 10 deaths. We don't know if we would prevent or how many of those relapses and deaths we would prevent. But there's a lot of operations with a relatively low yield. In the future, we hope to have blood tests that will tell us which men need surgery. And even right now, we're close to the point that we have blood tests that will detect residual cancer. And the chance is we worry about residual cancer in these patients and we don't have the blood test to pick it up. But the bottom line is in the meantime, the preferred management strategy is surveillance rather than surgery for most men. There's some men for whom RPLND may make sense in the center in this setting and some centers that will probably continue to recommend it for most men. I think this data really casts doubt on whether we ought to be doing this operation in these men as a routine practice as opposed to an exceptional practice for men who have particular characteristics. Thank you.

Greg Guthrie: Thank you, Dr. Gilligan. And now we can move on to answering some questions.

What is the average time expected to see a decline in PSA in patients treated with lutetium-177 PSMA?

Dr. Agarwal: I think this a great question and I think we're waiting for the manuscript published to go through the nuances of those data. Right now, what Dr. Michael Morris from Memorial Sloane-Kettering presented were the high-level data on pre-survival and overall survival and some secondary endpoints. We are anxiously waiting the full data in the form of a manuscript. And until then, I will not be able to answer that question. I would like to add that usually the median time, if you look at how -- for how long patients were receiving lutetium, it was 5 to 6 months. If I -- if my recollection is correct.

Greg Guthrie: Is radiation required prior to initiating chemo if there's tumor presence? And Dr. Gilligan, you responded. "We rarely use radiation therapy for testicular cancer at this time. Sometimes it is used for stage 1 or stage 2 seminoma as primary treatment instead of chemotherapy."

And I'll just read these aloud for our viewers here. If a patient has both prostate and bladder cancer, how do you decide which therapy should take priority, also, is the CPS typically included on the biopsy report? And Dr. Grivas, you responded, which I'll read here. "This is a bit of a complicated scenario that requires detailed discussion with a urologist and medical oncologist. Regarding CPS, the possible role is only in the first-line setting of metastatic disease to help somewhat decide between chemotherapy followed by avelumab maintenance and immunotherapy. However, it's not a perfect biomarker and not part of the pathology report, it's a special test that requires specific ordering."

I have a question for you, Dr. Zhang. Why do combination treatments seem to work better in kidney cancer? Wouldn't you have more side effects because you're taking 2 drugs at the same time?

Dr. Zhang: It's an interesting question. You know, our immunotherapy backbones seem to have good treatment benefit for these immune responsive diseases. The VEGF inhibitors that blocked blood vessel formation for many of our patients with clear cell kidney cancer, they tend to have an immunomodulatory role, so if we normalize blood vessels in the tumor microenvironment, the thought is that the T cells and immune cells can actually get into that space more readily. And so many of these blood vessel blockers are hypothesized to have increased immunomodulatory times of behaviors and the combination actually can be more effective than either agent alone, and we've certainly seen that in practice and really excited to see these combination strategies thrive and be standard of care for our patients now and first-line treatment. For the side effect question, you know, I do think that sometimes we do have to tease out which of the side effects is related to the oral treatment, the blood vessel blocker versus the immune therapy. But it's often experienced oncologists who are able to manage these side effects. We can try to tailor and see which of the side effects is due to which treatment and how to reduce or hold treatments when necessary.

Greg Guthrie: Great. I just got a follow-up question for you, Dr. Zhang. Are there any studies for papillary type kidney cancer with sarcoma?

Dr. Zhang: I would assume you're asking about sarcomatoid renal cell carcinoma within papillary, so for papillary type of kidney cancers, there are ongoing studies. For example, with FH mutations and FMH loss. For sarcomatoid disease, this is a special type of histology that can occur with any of our actual histologies of kidney cancer. And we know from our phase 3 trials in clear cell sarcomatoid renal cells that these tend to respond to the immunotherapy combinations. And so I would urge using an immune therapy combination in patients who had sarcomatoid renal cell carcinoma.

Greg Guthrie: Dr. Agarwal, here is a question for you. There were several studies in here that showed many patients did not receive combination ADT with other novel therapies, which you describe as the standard of care, including the one you discussed. Is this something that patients should proactively bring up with their doctors?

Dr. Agarwal: Fantastic question. I'm so glad you asked. The answer is yes: It is our responsibility as physicians and providers, but it doesn't hurt if our patients are educated and challenge us in our decision-making. It is a shared decision-making, it is not the doctor's decision. In my view, it's the patient's decision with help from the doctors. So, yes, please go do it. Doctors usually welcome that.

Greg Guthrie: Great.

Dr. Grivas: I see one for Dr. Gilligan about surveillance imaging that just popped up. [Is there any data on the benefits vs. risks for imaging based surveillance (CT, MRI, none) for longer-term follow-up periods (e.g. 2+ years)?]

Dr. Gilligan: Yeah, they're asking whether there's data on benefit versus risk for imaging-based surveillance and it's actually a very timely question in the sense that we're starting to get data that MRI is very accurate for this. And may likely become a substitute for CT scans at some point in the future. This is something we talk about a lot in terms of surveillance for testicular cancer patients, can we switch to MRI from CT because CT has ionization that can cause other cancers, and MRI does not. The good news is it looks like with current CT scanning, which is lower dose than older CT scanning, the risk of cancer from the CT scan seems really miniscule. Ultimately, it would be great to get it down to 0 and not do them, but we're still doing them. The switch to MRI is being held up by the fact that when you go in and get an imaging study for surveillance, your scans get looked at by a radiologist and also by the oncologist and all of us who do a lot of testicular cancer have multiple stories of catching stuff that the radiologist missed, and they also catch stuff that we miss. It goes both directions, and we're having 2 different people read the films to get a more accurate read. With MRI, most oncologists are not competent to read an MRI well and some radiologists are not great, and the centers where they have excellence have shown that MRIs are just as good as CT scans if read by fully qualified people. And the concern is: are they going to be skillfully read? So the switch to MRI will happen in the future, and I have spoken with people very recently about this that are practicing around the country and the people I talked to were not ready to make the switch because of the concern that stuff might get missed. And I think we can be reassured with the modern lower-dose CT scans, the risk seems to be quite small, and I look forward in the future to making that switch at some point.

 Greg Guthrie: And I think that's going to be our last question this afternoon. Thank you to all our participants for sharing this great research with us, as well as your expertise, it's been a real pleasure on this live webinar here.

ASCO: Thank you Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan.  You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

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Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net Content Team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today, we're going to be talking about genetic conditions linked to kidney cancer and what people with these conditions should know about genetic counseling. Our guests are Dr. Brian Shuch and Lauren Bear. Dr. Brian Shuch is the director of the Kidney Cancer Program at UCLA Health in Los Angeles, California. He is also 1 of the specialty editors for genitourinary cancers at Cancer.Net. Thanks for joining us today, Dr. Shuch.

Dr. Brian Shuch: Great. Thanks for having me.

Brielle Gregory Collins: Also joining us is Lauren Bear. Lauren Bear is the lead genetic counselor at the Familial Renal Cell Carcinoma and VHL Disease Clinic at Massachusetts General Hospital in Boston, Massachusetts. Thanks for joining us today, Ms. Bear.

Lauren Bear: Thank you so much for having me.

Brielle Gregory Collins: Before we begin, we should mention that Dr. Shuch and Ms. Bear do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to start, Dr. Shuch, what is the definition of a genetic or inherited condition?

Dr. Brian Shuch: Really, this is any condition that would develop that is really strongly influenced by somebody's genes that they would inherit from a family member. But there are lots of kind of complex definitions we can go into, but really anything that develops directly influenced or modulated by their genes that they inherit.

Brielle Gregory Collins: Thank you for defining that. And how are genetic conditions diagnosed?

Dr. Brian Shuch: So there are different ways, obviously, with the ability to have DNA sequencing done at a fraction of the cost from 10, 20 years ago, we can quickly and effectively sequence somebody's genes. But there are some times where we see patients that they have clinical features of a particular syndrome. And we have given patients a clinical diagnosis of that condition and follow them the same way if they meet some pre-specified criteria. But not every condition actually has a clinical diagnostic criteria.

Brielle Gregory Collins: And getting into those specific conditions a little bit, briefly, what are some of the most common genetic conditions that are linked to kidney cancer?

Dr. Brian Shuch: So there are about 18 different genes, which when inherited with a damaged copy, you potentially will have some increased risk. Some of them are the well characterized ones, which everyone is familiar with that have been around for decades. Most commonly, people are familiar with Von Hippel-Lindau, which has been described now about 100 years ago, but there are other conditions too. Birt-Hogg-Dubé, which is another common 1. The 1 that I study, hereditary leiomyomatosis and renal cell, we actually believe is the most common 1 based on newer data. But other ones, such as hereditary papillary renal cell, there's a bunch of ones linked to a hereditary paraganglioma syndrome called STH. But we have plenty of new and emerging conditions, and we're learning new things every year.

Brielle Gregory Collins: Thank you for running through all of those. And if someone is diagnosed with kidney cancer, what are some of the signs that they might have 1 of these genetic conditions?

Dr. Brian Shuch: So first and foremost, when you're with a patient, you look at their age and if someone has really early age of onset, it should be a red flag. Age alone is controversial whether you should do testing, but that should be a red flag. Whether someone has 1 tumor or more than 1 tumor obviously is important. Both kidneys or 1 kidney. But taking a family pedigree is very important. Most clinicians may just say any kidney cancer, but really understanding at least 2 or 3 generations can really help kind of outline somebody's inherited risk.

Finally, the pathology. There are about 20 flavors of kidney cancer, not all of them have the same type of risk. But we actually can learn a lot from a very outstanding pathologist that looks with special immunostains or they look at particular features under the microscope. And a lot of times, a good pathologist can pick this up. And when they do, we have very high likelihood of diagnosing someone with a hereditary form of kidney cancer.

Brielle Gregory Collins: Thank you. And as far as being diagnosed and how it affects the way someone is treated, can you describe how being diagnosed with a genetic condition may change the way kidney cancer is treated?

Dr. Brian Shuch: So not all types of kidney cancer are the same. It is 1 of the most diverse forms of cancers that we have. Just because they arise from the kidney does not make them the same. There are some which are very indolent and other ones which are extremely aggressive. So if I found a patient with a 1-centimeter kidney tumor and I knew it was sporadic, I may consider watching that patient and doing what's called active surveillance. If it's a patient who actually is a family member of 1 of our patients just diagnosed with HLRCC, that patient was placed on active surveillance and there's no way we would watch that type of tumor because it has much more aggressive biological potential. We would definitely recommend intervention for someone with that type of disease. Biology of the tumor really predicts behavior.

Brielle Gregory Collins: Thank you so much. And can you describe how common it is for someone to be diagnosed with inherited kidney cancer?

Dr. Brian Shuch: So that's a great question. It's something which is not really perfectly understood at this time. There's been very wide estimates, anywhere from 1% to maybe 8% of kidney cancer might have a very strong inherited component, whether it's due to a single gene that also may be somewhat variable, but I would say it's probably less than 10% of patients actually have a strong inherited predisposition. So we don't refer all patients for testing. And everyone's threshold to send someone for testing varies. But I think obviously, talk to your clinician. I think in this era where testing is fairly cheap and the risks are very low, I think as a default, most clinicians should err on sending patients to a genetic counselor and the genetic counselor can walk things through. Often the history that a clinician takes is somewhat insufficient. And I think the genetic counselors are really great at going through a 3-generation pedigree and then deciding whether testing should be pursued. So not everyone should be referred and not everyone referred should actually undergo testing. But I think the first step usually comes with recognition by the clinician. I'm interested to hear what Lauren thinks about this as well.

Lauren Bear: Yeah, I completely agree. It's a good point that we're more than happy to meet with any patient that a physician is concerned could have a hereditary kidney cancer condition. But exactly like Dr. Shuch described, not every family history is very high risk. And so, yeah, I completely agree.

Brielle Gregory Collins: And Ms. Bear, I want to get into a little bit about genetic counseling. So if a person is referred to genetic counseling, how can they best prepare for their appointment?

Lauren Bear: So during the visit, a genetic counselor will likely ask, as Dr. Shuch described, about their personal and family history to assess risk for 1 of these conditions. And there are some helpful things that people can prepare in advance for this appointment. First are factors related to their personal history. So like Dr. Shuch described, because some of these hereditary cancer syndromes are related to specific types of kidney cancer, it may be helpful to gather information about your own cancer diagnosis and your own personal medical history if it's not already included in the referral or the medical chart, and also gathering information about your family history. So asking some people to research with their family members to see who has had any cancer, what are the ages of diagnosis in their family members' medical history. And that often, again, like Dr. Shuch described, will be to ask about children, siblings, parents, and grandparents to create that 3-generation pedigree or family tree.

I think sometimes patients like to discuss the appointment in general with their family member before it happens, because the process of genetic counseling can often involve this option of genetic testing, which could have impact on family members. So beginning that conversation early with relatives can be helpful sometimes. And lastly, some patients like to talk to their insurance carrier about coverage of the appointment itself or even about the genetic testing, although very often talking about the actual genetic testing coverage will be discussed at the appointment with the genetic counselor. So working in advance to get some of these things together can be really helpful to prepare.

Brielle Gregory Collins: Got it. And as far as the meeting itself, what happens during and after the initial meeting with the genetic counselor?

Lauren Bear: Yeah, so overall, the genetic counseling appointment will involve a genetic evaluation during the initial session and then afterwards, a discussion about any test results and/or follow-up recommendations for the patient and their family members. So during the session, as I stated before, the genetic counselor will ask about this personal and family history and ask about other features that may be suggestive of a known hereditary kidney cancer syndrome. Sometimes that might involve a physical exam with a physician, depending on the indication or the clinic set-up. The genetic counselor will provide basic understanding of genetics and the basis of hereditary kidney cancer to make sure the information that is shared and the recommendations are all put into context for the patient and their family.

And then, based on the factors seen in the personal and family history, the genetic counselor will provide a risk assessment, which is a discussion of the possible genetic risk factors that could be explaining the kidney cancer or other cancers in the family. And as, again, Dr. Shuch described, to evaluate very often, this can include a discussion about genetic testing, which can be done on blood or saliva. Both are equally accurate, and it often can be performed via a multigene panel where we look at more than 1 of these conditions at once. But it's also important to realize that this testing is optional. So it is up to the patient if they would like to proceed with any of this testing. And an informed consent is a really important part of this discussion as well, to make sure the patient understands the benefits and limitations of this testing and to confirm if they do or do not want to move forward with the testing.

So that's overall what happens during the session and afterwards, if testing is performed, then genetic testing results are communicated to the patient. Depends on the clinic set-up how that's done, if it's through a telephone call, virtual visit, in-person visit. This may be together with the physician, again, depending on the set-up. But in this results disclosure, the genetic counselors and the medical team, they're equipped to convey these results with their patients. So they keep it in context with their own personal and family history and to help the patient adjust to the results, whatever the results are, because learning about genetic test results can sometimes be challenging. So a genetic counselor's role is to provide support and help the patient adjust however they can.

Brielle Gregory Collins: So it sounds like it's really a discussion between the patient, their genetic counselor, and the rest of their health care team to see if genetic testing is something that's right for them.

Lauren Bear: That's exactly right. That's exactly right.

Brielle Gregory Collins: Got it. And how does meeting with the genetic counselor help a person with kidney cancer and their family?

Lauren Bear: So when someone first learns there's a possibility of a hereditary reason behind their kidney cancer, many questions or feelings may arise from how this could impact their own health and how it could also impact the health of their family members. And this is all very natural. So the goal, as I stated before, is for the genetic counselor to help guide the patient and their family members to learn more about their risk and figure out who else might be at risk in their family. So, for example, if a positive test result is found or a diagnosis of a hereditary kidney cancer syndrome is made, the genetic counselor's skills are to identify the appropriate follow-up for that patient. So whether it's follow up with a physician to monitor for potentially another kidney cancer, or some other type of cancer, or some other symptom related to these conditions that Dr. Shuch described. And so that's part of when we're thinking about the genetic counselor's role with the patient and their own medical care, it's for that follow-up and helping them adjust.

When we think about for their family, a genetic counselor's role would be to help identify who might be at risk. So discussing cancer risk in families is not always the top of conversation. And so the role of the genetic counselor is to help work through ways to facilitate these conversations with family members. Not everybody in the family may be interested at that moment to do genetic testing. So working with a genetic counselor can be helpful in brainstorming ways to share this information with family. Other times, family members are very eager to pursue genetic testing at that moment, so genetic counselors can help set up those consultations or find local resources. So often, long-term relationships can be established with a genetic counselor and the family and the patient.

And then also, if a negative result is obtained, there's no gene mutation detected and the patient's not diagnosed with a known hereditary kidney cancer syndrome, the medical team and genetic counselor may also still be able to provide recommendations as far as screening for the family. So it's not to say only if a positive result is found are recommendations made. So those are kind of how I think about how a genetic counselor can impact the patient and their families in a situation like this.

Brielle Gregory Collins: Thank you so much for walking through that. So for someone who is diagnosed with 1 of these genetic conditions, what are some tips that you'd share about how they can discuss the genetic condition related to their kidney cancer with their family?

Lauren Bear: Every family is very different and the genetic counselors and the physicians, their specialty is to help walk a patient through how family members might react to this kind of information and what kind of materials may be helpful to have on hand when someone wants to share this information with their family members. Many genetic counselors supply family letters detailing the results that the patient is welcome to share with their relatives, certain handouts. We've had family meetings and conference calls, which can be helpful tools. And so really the genetic counselor is really trying to help the patients have the language to facilitate these conversations or to have their own understanding. So if they can absorb this information themselves, they may be more comfortable sharing it with their relatives. And that process might take a little while to adjust to this information, to give yourself some time to ask questions of your own medical team so you can educate yourself and then feel comfortable to share it. Sometimes these discussions happen with children who may be at risk for hereditary cancer, kidney cancer syndrome. So making sure to use age-appropriate language and also having more of like an ongoing conversation rather than a one-time conversation with children can be helpful. But as with anything, as questions come up, I always say, "Don't hesitate to reach out to the genetic counselors or your medical team. We're here to help."

Brielle Gregory Collins: That's all really helpful. Thank you so much for your time and for sharing your expertise today, Dr. Shuch and Ms. Bear. It was great having you.

Lauren Bear: Thank you for having me.

Dr. Brian Shuch: Thank you.

ASCO: If this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available. 

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today's podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across kidney, bladder, and prostate cancer.

This podcast will be led by Dr. Timothy Gilligan, Dr. Tian Zhang, Dr. Petros Grivas, and Dr. Neeraj Agarwal.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Institute. He has no relevant relationships to disclose.

Dr. Zhang is an associate professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Bristol-Myers Squibb and Merck, and has received research funding from Astellas Pharma.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. He has served in a consulting or advisory role for Bristol-Myers Squibb and Merck.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Bristol-Myers Squibb, Merck, and Astellas Pharma.

View full disclosures for Dr. Gilligan, Dr. Zhang, Dr. Grivas, and Dr. Agarwal at Cancer.Net.

Dr. Gilligan: Hi. I'm Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute. I'm joined today by Dr. Tian Zhang from the Duke Cancer Institute, Dr. Petros Grivas from the University of Washington and Fred Hutchinson Cancer Research Center, and Dr. Neeraj Agarwal from the Huntsman Cancer Institute and University of Utah. Today, we're going to discuss 3 ongoing clinical trials in kidney, bladder, and prostate cancer.

As you may know, clinical trials are the main way that doctors are able to find better treatment for diseases like cancer. Patient participation is vital for clinical trials. By participating in the clinical trial, you can directly help researchers develop better treatment, reduce side effects, or even reduce the risk of cancer altogether.

The 3 trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers panel from the Trials in Progress abstracts that were presented at ASCO's 2020 Annual Meeting. Because these are ongoing clinical trials, final results from these studies are not available yet. I'd like to note that none of us have any direct involvement with any of these trials. To view our full disclosures, please view the show notes for this episode on Cancer.Net.

We're going to start with Dr. Zhang discussing the trial CheckMate 914. Why don't we begin with who the study is designed for?

CheckMate 914 is a study in the adjuvant setting, so it's a study after patients have had their primary kidney cancers removed, and everybody needs to have a kidney tumor that's either 7 centimeters or larger or have extension beyond the kidney or any nodal involvement. So after their kidney tumors have been removed, this study really is in that timeframe after nephrectomy or after surgery with complete resection of their tumor.

Dr. Gilligan: What's the current standard of care for these patients if they're not on a trial like this?

Dr. Zhang: We often will compare against that standard which currently in the adjuvant setting we either do observation until disease recurrence or there is 1 oral treatment that's approved called sunitinib. But sunitinib really has some controversial data around it, and so it's not often used. And so currently, many patients are still observed as standard of care in the setting.

Dr. Gilligan: And so if a patient goes on this trial, what can they expect?  

Dr. Zhang: So patients who are enrolled to CheckMate 914 are randomized to either a combination immunotherapy called ipilimumab with nivolumab, which is approved in the metastatic setting for kidney cancer, or they're placed on placebo for these 2 treatments, or there is a third cohort that receives nivolumab alone with a placebo of ipilimumab. And so these patients are receiving either active immunotherapies or a placebo, which would be our current standard of care, sort of observation until disease recurrence.

Dr. Gilligan: So patients will either get the current standard, which is observation, or else they'll have 1 drug or 2 drugs if I'm understanding correctly?

Dr. Zhang: That's right.

Dr. Gilligan: What is the hope of this study? What is the outcome that we're hoping to see?

Dr. Zhang: The primary outcome of this study is disease-free survival, so that means time until disease recurrence for all comers. And we're really trying to prolong time until disease recurrence or time until metastasis for these patients. There are some secondary outcomes that are very important as well, so prolonging overall survival as well as the incidence of adverse events that are seen from these treatments. And then there is an independent radiographic assessment to look for disease-free survival intervals as well.

Dr. Gilligan: And the hope is that these treatments will prevent recurrence or at least delay recurrence then?

Dr. Zhang: That's absolutely correct, yes. And we have had 2 other adjuvant trials with immunotherapies in this space of atezolizumab and pembrolizumab, but those trials have finished accruing. And so this is the main ongoing and accruing trial that's looking at active immunotherapy options in this space.

Dr. Gilligan: What risks should patients be aware of that they might encounter if they go on this treatment?

Dr. Zhang: So with all immunotherapies, we talk a lot about the immune mediated adverse events and just the usual rundown of those. And in my clinic, we talk a lot about the common rashes. In the GI tract, it can cause some inflammation or colitis. Very rarely, it can cause some inflammation in the lungs or liver and then very commonly, endocrine dysfunction. So we watch pituitary, thyroid, adrenal, and pancreas function very carefully. But all of these side effects are well described for the ipilimumab, nivolumab combinations as well as nivolumab on its own in the metastatic setting. So most people should know what to monitor for and what we're looking out for and how to manage these toxicities.

Dr. Gilligan: Right. So these are drugs that have been in wide use for some years now, so we have significant experience managing the side effects is what I'm hearing you say.

Dr. Zhang: That's right.

Dr. Gilligan: Is this trial still open to patients?

Dr. Zhang: Yes. This trial is still accruing. It's a global study about to enroll up to 1,600 patients. So it's a very large global trial that is still active and still accruing patients. So I would encourage people and also oncologists to refer patients for the trial at a center close to them if possible.

Dr. Gilligan: And when might we expect results for a study like this?

Dr. Zhang: These adjuvant studies take a while to finish accruing and then it takes a while to finish seeing the data. So I would hazard a guess that we're still years away from seeing the data from this trial.

Dr. Gilligan: So once again, this is for people who have had surgery to remove a kidney cancer and looking at ways to reduce the risk of subsequent relapse. Well, thank you for summarizing that so coherently and succinctly. Let's move on now, and we're going to talk about the trial KEYNOTE-992 with Dr. Grivas. Dr. Grivas, who is this study designed for?

Dr. Grivas: So this is a clinical trial, a phase III clinical trial that applies to patients who opt to pursue what we call bladder preservation, which is an attempt to keep the bladder intact and still try to treat bladder cancer with concurrent use of chemotherapy and radiation. And this bladder preservation approach applies to a proportion of patients with bladder cancer still in the bladder but not spread. And as I mentioned before, the decision to pursue that strategy depends on particular patient characteristics, how the cancer looks on the CAT scans, and also how it looks under the microscope.

Dr. Gilligan: What is the current standard of care for these patients?

Dr. Grivas: So patients who are characterized as great candidates for this bladder preservation approach, because this does not apply to everybody with bladder cancer, the standard of care right now is patients undergo what we call a transurethral bladder tumor resection, which means that the urologists go through the urethra and they resect or remove or scrape, remove the visible bladder tumor, and then the patients undergo concurrent, meaning at the same time, chemotherapy and radiation.

Dr. Gilligan: How does the study aim to improve or change the standard of care? What would be different as a result of the study if it's successful?

Dr. Grivas: So this particular clinical trial, the KEYNOTE-992, is asking the question whether the addition of immunotherapy with 1 of those immune checkpoint inhibitors that activates the immune system, does this addition add value in the combination of chemotherapy and radiation? So the patients are being randomized by a computer system to either getting chemotherapy-radiation, as is the standard of care that we just discussed, or chemotherapy plus radiation which is standard of care, plus the addition of this drug called pembrolizumab, which is an immunotherapy aiming to activate the immune system.

Dr. Gilligan: And it's given at the same time as the chemotherapy and radiation on the study?

Dr. Grivas: That is correct. It's given at the same time. And then there is also some—what we call continuation of pembrolizumab for some time after the end of chemotherapy and radiation, and pembrolizumab in this study is given every 6 weeks.

Dr. Gilligan: And what makes people think that this might be helpful to add this additional treatment?

Dr. Grivas: The notion is that the addition of immunotherapy to chemotherapy-radiation therapy has the potential to make the chemotherapy, radiation therapy work better. What happens sometimes when you give chemotherapy-radiation, this can actually result in a killing of some cancer cells and the contents of those cancer cells can be released, and they may be recognized by the immune system and stimulate the immune response. So if you combine that chemotherapy and radiation with immunotherapy with this agent that stimulates the immune system, the assumption is that this may work better compared to chemotherapy and radiation alone. But we have to do this trial to confirm whether this is true or not.

Dr. Gilligan: So patients going on the study, basically, either they'll get the standard of care, which is the chemotherapy and radiation, or the standard of care plus the addition of immunotherapy to see if that results in better outcomes. Am I understanding that correctly?

Dr. Grivas: That's exactly right. And the outcomes are being measured by how many patients maintain the bladder intact, in place without the need to remove it, without the need for cystectomy. And also, at the same time, we want to see if those patients can maintain a cancer-free status, so whether the treatment results in a cancer-free state and whether we are measuring a recurrence as Dr. Zhang mentioned before, if the cancer comes back. And also, of course, we measure how many patients are alive over time. So the goal is to see if we can improve upon the rate of patients with no cancer coming back, no recurrence, and being able to keep the bladder intact if possible.

Dr. Gilligan: So for both of these trials, the question seems to be if we intensify treatment, can we increase the cure rate and keep patients cancer-free longer?

Dr. Grivas: That's exactly right, and that's the promise or the assumption of this trial, whether the addition of immunotherapy to chemotherapy and radiation can improve those chances.

Dr. Gilligan: What are the known risks that patients should be aware of?

Dr. Grivas: As Dr. Zhang mentioned before, every time we have the immunotherapy in clinical trials or in clinical practice, we have to do a good job educating, of course, all the medical providers, team members, and the patients for early recognition and reporting of what we call immunotherapy-related potential side effects. And as we discussed earlier, any organ of the immune system could be a target of an activated immune system. The reality is that if the side effects from immunotherapy happens, usually it's a mild to moderate degree and usually can be managed by holding of the immunotherapy drug and maybe sometimes give some steroids to cool down the immune system. Obviously, we need to be extra vigilant, and I always err on the caution of overeducated patients to avoid underreporting so we make sure we know ahead of time if a side effect happens.

Dr. Gilligan: Is there any reason to be worried that immunotherapy could make the side effects of chemotherapy and radiation worse?

Dr. Grivas: It's a great question, and we have to look in that during the course of the trial. The notion is so far, based on the available data, that it's safe to combine chemotherapy, radiation, and immunotherapy. There have been some early data suggesting that, and this is reassuring. At the same time, we need, again, to be extra vigilant, again, over-educating our patients to report any changes so we can be able to compare the potential side effects in the 2 groups. But so far, it seems to be a feasible strategy.

Dr. Gilligan: Good. And is this trial still open for patients?

Dr. Grivas: Yes, it is open and accruing patients actively, and I think it's a great opportunity for patients to discuss with their providers, urological oncologists, medical oncologists, radiation oncologists, whether they could be good candidates for this bladder preservation approach, if that's a good fit for them and the particular cancer at hand, and if so, whether they can be candidates for this trial or another trial called SWOG 1806, which is in the same space and setting.

Dr. Gilligan: And when might we expect results from the study?

Dr. Grivas: It may take time because this trial is still early in the accrual process. It may take a few years. The current estimate is probably 2026, so 5 years from now. However, the faster these trials accrue, maybe the faster is to have the results. So this might have been overestimation, but it depends with how quickly the study will accrue patients. It's a very exciting study and definitely, I encourage patients to discuss this and the SWOG 1806 with their providers.

Dr. Gilligan: Thank you very much. We're going to move on now, and Dr. Agarwal will tell us about the KEYNOTE-991 study. Dr. Agarwal, who is this study designed for?

Dr. Agarwal: This is a study which is designed for patients with newly diagnosed metastatic castration-sensitive prostate cancer. In simple words, this is for those patients who have been diagnosed to have a prostate cancer which has gone to different parts of the body.

Dr. Gilligan: And what's the current standard of care for these patients if they don't go on the study?

Dr. Agarwal: Fortunately, the current standard of care has gone through a paradigm shift in the last 5 to 6 years. It started with chemotherapy with docetaxel being approved for these patients in 2014 with 2 positive clinical trials showing benefit for docetaxel chemotherapy as far as improvement of survival is concerned. After that, 3 more drugs known as novel androgen axis inhibitors, so deeper blockade of androgen pathway, which is a driver behind prostate cancer progression. So these 3 drugs, abiraterone, or also known as Zytiga, enzalutamide, also known as Xtandi, and apalutamide, also known as Erleada. These 3 drugs and chemotherapy are currently approved agents for our patients with newly diagnosed metastatic prostate cancer.

Dr. Gilligan: And what is this study looking at to potentially change that or to add another option?

Dr. Agarwal: So this study is using the backbone of androgen deprivation therapy, which is standard testosterone suppression therapy, plus enzalutamide or Xtandi. And then patients who are receiving the standard of care therapy with standard testosterone suppression therapy, plus enzalutamide, they will be randomized to pembrolizumab versus placebo. Pembrolizumab is an approved immunotherapy for multiple cancer types and pembrolizumab, also known as Keytruda, works by activating our immune system to fight against cancer cells. In a way, this study is actually testing whether addition of this novel immunotherapy pembrolizumab to existing regimen of androgen deprivation therapy plus enzalutamide is going to improve survival outcomes.

Dr. Gilligan: What do we know about immunotherapy and prostate cancer?

Dr. Agarwal: So far, immunotherapy, as we call them, immune checkpoint inhibitors, many of them are approved for multiple cancer types. They have not been successful as single agents in the context of advanced prostate cancer. So this is a trial which is testing whether immunotherapy, the pembrolizumab is going to be effective in combination with enzalutamide and testosterone suppression therapy.

Dr. Gilligan: So patients will get the standard of care therapy either way. And then the question is, does adding immunotherapy make it even more effective than it is without it? Is that correct?

Dr. Agarwal: That's true. The primary end points of the trial are overall survival and radiographic progression-free survival, which basically means the investigators are going to look for improved survival, overall survival, and delaying of disease progression by adding pembrolizumab.

Dr. Gilligan: And we've already discussed the risks of immunotherapy on the previous 2 trials, but can you tell us again for patients who are particularly interested in this study what risks should they be aware of?

Dr. Agarwal: So pembrolizumab belongs to a class of drugs known as PD-1 or programmed death 1 receptor inhibitor. Usually, this class of drug, as a class, these are highly well-tolerated drugs and only a small number of patients, I would say less than 5% of patients, would develop grade 3 or 4 side effects which will require treatment with corticosteroids like prednisone. And those side effects usually happen when these immune checkpoint inhibitors are able to activate the immune system beyond desired limits. And when the immune system is activated to very high levels, the immune system can attack our own body and can result in diarrhea, skin rashes, liver enzyme abnormalities, and if not controlled in time can lead to hepatitis, which is inflammation of the liver, inflammation of the lungs causing pneumonitis or cough, dry cough mostly. So these are the common grade 3, 4 side effects which happen in up to 5% of patients with pembrolizumab.  

Dr. Gilligan: Just for our listeners in case they're not familiar, when you talk about grades 3 and 4 toxicities, what should they understand that to mean?

Dr. Agarwal: In simple words, I would say grade 1 and 2 side effects are the ones which do not require any systemic therapy with steroids. Patients can go on with their daily activities without much problems. And mostly, these are controlled with medications which are over-the-counter. Even if we use prescription medicines, they're usually not able to affect the patient's overall lifestyle or quality of life. So these are the side effects which are pretty easily manageable mostly with over-the-counter drugs, symptomatic drugs, and patients lifestyle and quality of life are usually not affected by the side effects. And grade 3 and 4 side effects are those which require intensive therapy, in this context, with prednisone or corticosteroids sometimes requiring hospitalization and requiring multidisciplinary care with other specialists who are specializing in gastroenterology or pulmonology or on many other specialties. So that's how I would like to simplify the definition of grade 1, 2 versus grade 3, 4 side effects.

Dr. Gilligan: That's great. Thank you very much. Is the trial still open for accrual? Can patients still go on it?

Dr. Agarwal: Yes. Yes. Trial actually just opened for accrual, which is good news for our patients. And I would like to highlight that patients who have been diagnosed with newly diagnosed metastatic prostate cancer and they have started hormonal therapy like androgen suppression therapy, they still have 3 months to enroll in the trial. So if you have been diagnosed with metastatic prostate cancer and if you have started the treatment with testosterone blockade therapy, you can still go on the trial. You have 3 months to go on this clinical trial. And if you have started chemotherapy with docetaxel, which is a standard of care for our patients with this diagnosis, you can still go on the trial after receiving up to 6 cycles of chemotherapy with docetaxel. So this trial allows actually patients to go on the trial for up to 3 to 6 months after being diagnosed with metastatic prostate cancer.

Dr. Gilligan: So that's very helpful to know. At the conclusion of chemotherapy, they would then start the enzalutamide and either the pembrolizumab or placebo?

Dr. Agarwal: That's correct.

Dr. Gilligan: Well, great. And when do we expect to see results from the study?

Dr. Agarwal: So as we know this, which is great news for our patients, survival has gone up by almost 2 to 3 fourths over the last 10, 15 years, and in this disease setting, any trial takes up to 5 to 6 years to show results. So I estimate based on the available information on the ClinicalTrials.Gov website, the trial is scheduled to finish in 2026.

Dr. Gilligan: I see. Well, great. So thank you very much. Thank you all 3. That's hopefully a helpful summary of these 3 important new trials.

Dr. Agarwal: Yes, it's a pleasure to be here, Tim.

Dr. Grivas: Thank you so much.

Dr. Gilligan: Thank you. Thank you for listening to this podcast. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team.

ASCO: Thank you, Drs. Gilligan, Zhang, Grivas, and Agarwal.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Dr. Lidia Schapira and Dr. Daniel Mulrooney discuss a study published in the Journal of Clinical Oncology about mental health outcomes for AYA cancer survivors and how young survivors can get the mental health support they need after cancer.

Dr. Schapira is Associate Professor of Medicine at Stanford University School of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute. She is also the Cancer.Net Editor in Chief. Dr. Mulrooney is an Associate Member in the Division of Cancer Survivorship at St. Jude Children's Research Hospital. He is also the Cancer.Net Associate Editor for Pediatric Cancers.

View disclosures for Dr. Schapira and Dr. Mulrooney at Cancer.Net.

Dr. Schapira: Welcome to this Cancer.Net podcast. I'm Lidia Schapira, the editor-in-chief, and with me today is Dr. Dan Mulrooney, an expert in cancer survivorship in children's cancer. Welcome, Dan.

Dr. Mulrooney: Thank you, Lidia. Nice to be here.

Dr. Schapira: We have no disclosures for this podcast. And the article that was just published in JCO by Dr. De is what has prompted this conversation with Dan. In that article, scientists from Canada were interested in looking at the incidence and predictors of mental health outcomes among cancer survivors, of adolescent and young adult cancers. So they used a large database, and they looked at what happened to those adults who were diagnosed when they were between 15 and 21 years of age and had survived at least 5 years since their cancer. So they were now adults. What they were interested in were the mental health episodes that were either outpatient mental health problems, mostly anxiety, that were diagnosed in these cancer survivors and also, severe psychiatric episodes such as hospitalizations for a disease called schizophrenia and other important psychiatric illnesses. And they compared them to adults that were matched but did not have a history of cancer. And surprisingly, perhaps, or not so surprisingly, and this is what we'll discuss, they found that the survivors of cancer had more mental health problems. So there was a 30% higher rate of outpatient mental health visits, mostly for anxiety, and a 20% increased risk of a severe psychiatric episode as compared to these matched controls. So, Dan, I first wanted to get your reaction to this, and please feel free to correct my analysis if your interpretation was slightly different.

Dr. Mulrooney: No, it really isn't. Thank you, Lidia. It's a really important article concentrating on a group of survivors that we really already know are at higher risk for adverse mental health outcomes and psychosocial risks following their cancer therapy. But what's so interesting is they were able to combine large data sets. They were able to compare these survivors to the general population, which is very relevant for health care providers taking care of these patients in the community. And in addition to that, what I thought was particularly interesting is their ability to look at both outpatient visits and those more severe mental health issues that require an emergency room visit or require admission to the hospital. I think this is very informative information about this high-risk group of survivors and hopefully will be instructive if we can interpret this and turn this into services that we can direct to these patients.

Dr. Schapira: I found it interesting, Dan, also that they said that they only captured the mental health visits in the outpatient setting that were delivered by physicians because of the data. So, in fact, visits with social workers or psychologists did not even make it into these statistics. And that suggests to me that there may be even more problems that were not captured by these numbers.

Dr. Mulrooney: I think you're absolutely correct on that. If anything, these numbers are an underestimate of the issues and the problems that may be out there. It's only those that made an appointment and went to a mental health care provider. They missed social workers. They missed other social networks, ministers, religious organizations that might be providing help as well. And of course, we're talking about a young adult population that may not always reach out for these services. And so, this group did reach out. So we probably have the more severe group represented here, but we're missing a large population underneath this. I suspect you're absolutely right.

Dr. Schapira: And so, if we think about what we can do with his information, how we can think about guidelines, assessments, and support, let's think back to when these young adults and adolescents are first diagnosed. I was also struck by the fact that there was a difference with more mental health problems in those treated in adult cancer centers than those that were treated in pediatric cancer centers. Can you tell me what may account for those differences?

Dr. Mulrooney: That's a very interesting question and fact that came out of this paper. And I suspect there are probably a number of reasons. I think globally, this paper looks at mental health issues in cancer survivors, which we have to separate from mental health issues in patients going through active cancer therapy. There may be quite a bit of overlap. There may be some similarities. But I suspect, particularly in the AYA population, the issues that they encounter as a survivor are different than those that they struggled with maybe as a patient. And they saw this difference, particularly for outpatient visits, based on where they were treated. One thing to point out is the majority of these survivors were actually treated in the adult cancer centers. Because in Canada, if you're over age 18, you're considered an adult and you're treated at an adult cancer center. So there was a smaller population, I think it was only about 25% to 27%, that were actually treated in pediatrics. And certainly, the focus and the culture of care is different between pediatrics and adult medicine. And I suspect there may be some differences in survivorship support and care. And these survivors, they were relatively soon after receiving their care and those in the pediatric community are probably receiving, I suspect, maybe more follow-up, a survivorship program, probably a little bit more structured, and hopefully a survivorship program that has social work support or psychosocial services provided. Now, I can't say that the adult centers don't have that, but of course, the population is much larger, and the visits and that culture is very different than they receive in pediatrics. So it is possible that some of those early services and supports are just not available to that population.

Dr. Schapira: So let me pick your brain about this a little bit since you are immersed in this world. What does it take in your mind to create the best possible environment for these young adults to thrive after cancer or to have an opportunity to receive all the mental health support that they need in order to move on with their lives?

Dr. Mulrooney: I think number 1 is to recognize it as an issue. In particular, we know that this AYA population is considered a high-risk population for mental health issues after cancer. And so number 1, we really need to recognize that. And this paper draws our attention to that very nicely, that it is an issue, there's a high prevalence of mental health issues after cancer therapy. But in our survivorship clinics, we need to address the medical and chronic health concerns after cancer therapy, but we can't forget these psychosocial issues. And how does that affect this individual survivor? They're struggling with lots of issues after cancer: fear of recurrence, fear of a second cancer, maybe body image issues, maybe health conditions that their peers at this age are not encountering. And so in addition to treating those and doing appropriate surveillance, we should really also be doing mental health surveillance and screening, and identifying appropriate referrals for them to address those issues.

Dr. Schapira: So, Dan, how do people like us who are not trained in mental health, what should we be doing and thinking about as oncologists or even as primary care physicians who see these patients? What can we do?

Dr. Mulrooney: Yeah, I thought a great deal about that when reading this because even in primary care, there's at least some general screening for mental health or depression. Most primary care providers, at least mine, hands me a little questionnaire that I fill out while I'm in the waiting room. Obviously we need to do that, but perhaps we need to take it a step further in this unique population, to maybe ask the appropriate questions in a survivorship clinic. Hopefully, we have social work support. Not all centers will have that. Obviously, there's going to be access issues. And in the United States here, there's probably financial issues that maybe didn't occur here in Canada. But we really need to advocate for taking those questions a little bit further, digging a little bit deeper, and really having a social worker available, maybe to do that screening in person, maybe not do it on paper in a group that we know is high risk.

Dr. Schapira: So that was 1 of the things that I also thought about as I was reading this, this idea that screening tools are great, when you think that what you're screening for has a relatively low prevalence. But if, in fact, this is so important, maybe an assessment done by a professional who's trained may actually take us a little bit further and help us so that we don't miss people. I know many screening efforts, for instance, where the data is captured, but then there is no link to a solution or a referral. And it's not that people don't mean well, but there are all sorts of reasons why things fall through the cracks, which is sad. Whereas if there were a relationship and an assessment done by a professional, I feel then we would be more-- our default would be more to ask, to support, and to keep asking. Because 1 of the things I think the authors also tell us is, you need to keep doing this over the course of many years. Is that your understanding as well?

Dr. Mulrooney: Absolutely. All of us were trained as oncologists, and we feel like we maybe don't have the skills to address this. But we certainly have the ability to ask and delve a little bit deeper. We know how to take a history, we know how to-- we take care of patients in very critical realms. And so we certainly are comfortable asking difficult questions. And mental health questions should be really no different from that. And, an important thing I noticed in this paper is 1 of the predictors of a mental health issue for the survivors was a preceding mental health issue even before diagnosis or going through therapy. So are we missing them all the way along? And maybe we should be intervening or addressing this when they're our patients in our cancer center, and then not miss that transition to appropriate survivorship care, and appropriate psychosocial care after that.

Dr. Schapira: I couldn't agree with you more. I think between the 2 of us, we could design the perfect cancer care system, right, where we reach out to these adolescents and young adults. And, in some cases, I imagine in the younger ones, there's also the parents to consider at the time that they're getting treated, right? And then maybe those relationships as they grow into adulthood also change. And there may be, sort of, a disruption in what we think of as the family unit or the supports available to that young person so it's very complicated. Do you have any advice, given the work that you do in this survivorship clinic that you've had, how can we even begin to do this? To reach out to everybody and make sure that people feel connected to you, but then also that when you let them go, that they can find the support they need?

Dr. Mulrooney: What a struggle it is, particularly with these young people who are growing into their own, becoming more independent, want to take more responsibility, but then are struggling with so many of these health care issues, whether they're physical or mental. And family support and the family unit has to be considered, particularly with the younger population. And not only the mental health of the survivor, but the mental health of the parents or the family who may have their own issues preceding cancer therapy, or may be struggling with how to take care of my child after cancer, or this fear of recurrence themselves. And oftentimes the parents may have a harder time than the young person does. And we have seen both, post-traumatic stress disorder, but also post-traumatic resilience in some of these patients. They really feel they've come through something and it's made them stronger and it's changed their outlook on life. In our clinic, we make sure that we at least have them see a social worker when they come into the survivorship clinic, and then again, as there may be mid-adolescence and a year or 2 before they're going to graduate or leave our care. So that we're addressing those issues or identifying those issues. And then that gives us at least a year or 2 to try to find the services locally, wherever they live, for them. The handoff in that transition is very difficult. And I won't lie, I've been concerned about the transition for a long time, as you know. I think it's an area we really need to improve upon. We need more buy-in from the medical community across the board, maybe more research in that area.

It's a real struggle, but we can't just finish their survivorship care and not make sure that they're not connected again locally because the care continues, and the paper showed that that the risk continued to increase and went up with time from diagnosis. So it's a real struggle, it's just really hard.

Dr. Schapira: You just described the challenge that we all face so beautifully. And so, my final question to you is about your experience with young cancer survivors during this last year, with the COVID pandemic. With the isolation and all of the mental health issues that we've heard about just among young people in general, what have you found? I imagine you're going to tell me that there is enormous variation, but I'd love to have you share with our listeners a little bit of what you've learned.

Dr. Mulrooney: It has increased the stress on cancer survivors, and it's made-- the pandemic's made life difficult for everybody. But again, now if we're talking about a population who has survived cancer, who may have some chronic health effects related to that, and they've called us and they said, "Am I at increased risk? What should I do? Do I need to do something different to protect myself?" And so far, we don't know. The data really aren't mature enough to understand if a survivor of cancer is at a higher risk than somebody in the general community. Certainly, if they're on immunosuppressive medications or certainly if they have chronic health conditions, we suspect they're at higher risk, just as you might see in the community, but particularly with an older population.

Access to care is certainly more limited, and so issues, just as we're talking about here, mental health services are magnified, and it's harder to reach out and get those services. I was thinking a great deal about that when reading this because, in some ways, they may be able to get services a little bit more quickly because it's all being done by telehealth, and these encounters are probably not being done in person. On the other hand, it's disrupted scheduling and access. So, again, I worry that there's a large population that was missed even in this study, but a large population now that's being missed and not receiving services because of the pandemic. Hopefully, as this begins to ease, we can start attacking that problem and getting to more and more of those people.

Dr. Schapira: Are there resources for survivors, especially now in the time of the pandemic, someplace they can turn to if they want to learn more about this topic?

Dr. Mulrooney: There are a number of resources, and particularly with the Children's Oncology Group, has developed what they call Health Links and documents in lay language that can be a resource for survivors who are struggling with physical illness and also mental health illness. The website is called survivorshipguidelines.org, and the link is to the Health Links on that page. There's a Health Link particularly for mental health issues following cancer, and also 1 for issues related to the COVID pandemic that I hope survivors might find helpful.

Dr. Schapira: Well, thanks, Dan, it's been lovely chatting with you. It always is. I know I've learned a lot and I hope this is useful to our listeners as well. Thanks for everything and thanks for all you do every day.

Dr. Mulrooney: Thank you very much. It was nice to be here.

ASCO: Thank you, Dr. Schapira and Dr. Mulrooney. Find more resources for young adults at www.cancer.net/aya. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Norah Lynn Henry discusses new research presented at the 2020 San Antonio Breast Cancer Symposium, held virtually December eighth through eleventh. Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. View Dr. Henry's disclosures at Cancer.Net.

ASCO would like to thank Dr. Henry for discussing this research.

Dr. Henry: Hi. I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates from the 2020 virtual San Antonio Breast Cancer Symposium. My institution enrolled patients in the first trial that I will discuss, otherwise, I have no conflicts of interest for any of the trials that I will talk about.

Today, I'm going to focus primarily on treatment of non-metastatic breast cancers that are hormone receptor-positive and HER2-negative. These studies highlight personalizing treatment for individual patients. In the first and last trials I will mention, the studies examine whether it is possible to give less treatment without substantially increasing the risk of breast cancer recurrence. In general, giving less treatment leads to fewer long-term toxicities and better quality of life. In contrast, the other 2 trials I will mention are examining adding more therapy to standard treatment with the goal of increasing breast cancer cure rates for patients at high risk of recurrence without causing too much additional toxicity.

One of the biggest stories in this meeting was the result of the RxPONDER trial. This trial enrolled thousands of women with hormone receptor-positive, HER2-negative breast cancer, who had cancer present in 1 to 3 lymph nodes under her arm. The standard treatment for patients who have lymph node positive breast cancer has been to recommend chemotherapy in addition to anti-hormone therapy. This trial is testing whether that is actually the best treatment. In this trial, every patient's tumor was tested with a test called Oncotype DX and was given a recurrence score ranging from 0 to 100, depending on how quiet or aggressive the tumor is. Women whose tumors had a score between 0 and 25, which is at the low range, were randomized, like flipping a coin, to either receiving the standard, which is chemotherapy followed by anti-hormone therapy, or to just anti-hormone therapy alone.

The patients were then monitored to see if they developed recurrence of their breast cancer. Overall, there was no difference between the groups. Meaning that adding chemotherapy to the treatment did not provide a benefit in terms of reducing risk of recurrence. When they divided the groups by lower or higher score, it still didn't make a difference. However, when they divided the women by menopausal status, it did. Women who were post-menopausal when they were diagnosed with breast cancer did not get any benefit from chemotherapy. In contrast, women who were pre-menopausal did get a benefit from chemotherapy. And in fact, they lived a little longer than those who only got anti-hormone therapy. However, there's still a question about how much of the benefit is from the chemotherapy itself acting directly on the cancer and how much is from the chemotherapy putting the ovaries to sleep, which also treats the cancer, although indirectly.

Therefore, the take-home message for a post-menopausal woman with hormone receptor positive, HER2-negative breast cancer who has 1 to 3 involved lymph nodes, is to talk with her oncologist about whether her tumor should be tested to help make a decision about chemotherapy as opposed to just assuming that she needs chemotherapy because her lymph nodes have cancer in them. For pre-menopausal women, it's a little less clear, unfortunately. In that case, it is important to talk about the pros and cons of chemotherapy with her oncologist depending on her exact situation, including her age and the amount of cancer in the breasts and the lymph nodes. Hopefully, we will learn more about how best to treat pre-menopausal women when additional analyses are performed on the data from this trial.

Also related to non-metastatic hormone receptor positive, HER2-negative breast cancer, updates on 2 trials related to the use of adjuvant CDK4/6 inhibitors on patients with high risk to breast cancer recurrence were presented. The CDK4/6 inhibitor medicines are routinely used to treat patients with metastatic breast cancer since the combination of these drugs plus anti-hormone therapy results in longer time to disease worsening compared to just anti-hormone therapy alone. Therefore, these drugs are now being tested in the non-metastatic setting to see if they increase the likelihood of cure of breast cancer.

In the first trial called MonarchE, addition of abemaciclib, which is a CDK4/6 inhibitor, to standard aromatase inhibitor therapy decreased the likelihood of recurrence of invasive disease in patients at high risk of disease recurrence. However, the length of follow up of the patients who participated in the trial is still rather short, and so far, adding the treatment has not shown that people will actually live longer. The other trial that was presented, called PENELOPE-B, studied a similar CDK4/6 inhibitor medicine called palbociclib in a similar setting. In that trial, although the benefits looked promising early on, with longer follow up, the benefits have unfortunately disappeared. Therefore, although the results of MonarchE look very promising, we still need more follow up to determine the actual benefit to patients. Also importantly, this drug is not currently approved for treatment of early stage breast cancer at high risk of recurrence, and it is not currently included in treatment guidelines. So at this point, it is unlikely that the drug costs will be covered. We await additional updates from these and other trials of similar design in order to know whether patients should be receiving these drugs as part of their breast cancer treatment.

And finally, to change gears a little to patients who are at low likelihood of disease recurrence, we also got an update of the PRIME II trial. This trial asked whether radiation therapy is beneficial in women over the age of 65 who have small lymph node-negative, hormone receptor-positive breast cancer. In this trial, most patients had tumors that were smaller than 2 centimeters, and all underwent lumpectomy and were planning to take adjuvant anti-hormone therapy. Patients were randomized either to receive radiation therapy or to not receive radiation therapy. Radiation therapy is the standard of care in this setting. Consistent with their earlier results, not having radiation therapy did increase the risk of local recurrence a little from 1% to 10% over 10 years. And this really highlights that although the risk of local recurrence in the breast is a bit higher if a patient does not have radiation therapy, it still has a 90% chance of not having a recurrence during that 10-year period. Also, not getting radiation did not affect survival from breast cancer. It is important to note that most patients likely took endocrine therapy, and it is thought that risk of recurrence is higher if both radiation therapy and endocrine therapy are omitted. Therefore, patients over the age of 65 or 70 who have small hormone receptor-positive breast cancers should talk with their surgeon, medical oncologist, and radiation oncologist about the benefits and risks of radiation and make a personal decision about whether or not to undergo radiation therapy.

Well, that's it for this quick summary of this important research from the 2020 virtual San Antonio Breast Cancer Symposium. Overall, we continue on a fast track in breast cancer with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you.

ASCO: Thank you, Dr. Henry. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Michael Williams talks about new research and advances in the field of lymphoma, including 3 recent U.S. FDA drug approvals. The research discussed was presented at the 2020 American Society of Hematology Annual Meeting, held virtually December fifth through eighth. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center. He is also the Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. View Dr. Williams' disclosures at Cancer.Net.

Dr. Williams: Hello. This is Dr. Michael Williams. I'm professor of medicine at the University of Virginia Health System in Charlottesville, Virginia, and I'm pleased to welcome you to this podcast for Cancer.Net. I'm reporting on some of the exciting updates that were just presented at the American Society of Hematology Annual Meeting. Typically, this is a meeting of 30 or 35 thousand clinicians and investigators from around the world. This year, as with so many meetings, we met virtually, but I would say very successfully done. Lots of exciting new data, and I'll try to give you a glimpse of what some of the progress has been. Before I start, I'll mention a few disclosures. So I have research grants that are awarded to the University of Virginia for clinical research from Celgene, Janssen, Pharmacyclics, and TG Therapeutics. And I have served as a consultant for Celgene, Janssen, and Pharmacyclics, as well as Kyte Pharmaceuticals, which is a division of Gilead.

So the advances this year weren't just at the meeting. There were 3 new drug approvals in the past 6 months for lymphoma. Tazemetostat, which is an EZH2 inhibitor, was approved for relapsed/refractory follicular lymphoma patients who have a mutation in a gene called EZH2. So they showed good tolerance of this treatment with high response rates in these patients with the mutation. So it provides another important treatment option for people with relapsed follicular.

A new approval for relapsed diffuse large B-cell lymphoma was a novel monoclonal antibody called tafasitamab given in combination with lenalidomide that also showed good responses and generally very good tolerance in people with relapsed aggressive lymphoma. So a welcome addition again to our treatment options. And then finally, a chimeric antigen receptor T-cell therapy or CAR-T was approved for relapsed/refractory mantle cell lymphoma. And I will say a bit more about that agent as we get into the discussion about CAR-T therapy for mantle cell.

The first abstract presentation that I want to mention is in chronic lymphocytic leukemia or small lymphocytic lymphoma which, of course, is really 1 disease. It's just a spectrum of whether you have more of a leukemic phase or a lymph node enlargement component to your disease. Treatment in CLL has really shifted in recent years away from cytotoxic chemotherapy and is now well established that most patients needing treatment, whether for newly diagnosed disease or for patients who have been previously treated with other regimens, that targeted therapies such as Bruton tyrosine kinase inhibitors or a BCL-2 inhibitor venetoclax can get very high response rates.

There's been interest among many groups in testing combinations of targeted drugs, and we heard an update of a report called the CAPTIVATE study that combines ibrutinib plus venetoclax. Both of these are oral agents. As a randomized study for patients with CLL who need treatment and have not been previously treated for their CLL. And what this study did was provided a combination of the 2 drugs as first-line therapy, and they showed that after a period of about 12 cycles of combined treatment, that you had very, very high remission rates. They used a very sensitive method, a molecular method, to detect minimal residual disease. And if patients were in a deep molecular remission, so undetectable MRD at the end of treatment, they were randomized to continuing with either no therapy or with just ibrutinib alone. And it was found that after a year, there was really no difference. So it shows that with combination therapy, you can get a deep enough remission to have a durable and ongoing response for those patients. They also randomized those who still had detectable residual disease to either ibrutinib alone or a combination of ibrutinib plus venetoclax, and they showed that their outcome at the end of treatment was likewise similar. So it shows a very good non-cytotoxic-chemotherapy-based approach to treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma.

So the second item I wanted to bring your attention was for another form of indolent or low-grade non-Hodgkin lymphoma called Waldenstrom macroglobulinemia which is also identified as lymphoplasmacytoid lymphoma. And in this study, they used a combination of ibrutinib plus rituximab, an anti-CD20 monoclonal antibody, versus placebo with rituximab alone. So this study is reporting now long-term follow-up with more than 5 years since the onset of treatment initiation in 150 patients. So rituximab by itself was a standard of care for patients with Waldenstrom at the time the study was designed. We now know that ibrutinib can give very good responses, especially when given in combination with rituximab. And indeed, they showed that now with 5 years of follow-up, that the response in terms of the serum IgM level, which is a marker for activity of this disease, improvement in anemia as well as objective response rates were much improved with the combination of ibrutinib plus rituximab versus rituximab alone. They also showed that there was a delay in the time that a patient needed another line of therapy for progressive disease when they had that combination. So important long-term follow-up there confirming the safety and activity of ibrutinib and rituximab for that disease.

And then finally, I'll give an update on 1 of many reports at this meeting on CAR-T cell therapy. So just to remind those of you who may not be so familiar with this, it's a technique of cellular therapy, wherein a patient who's got disease progression with follicular lymphoma or mantle cell lymphoma or diffuse large B cell lymphoma, the patient undergoes a procedure where T-cells are removed from their blood, and then in the laboratory, they are reprogrammed to attack the patient's lymphoma cells. So the reprogramming is done, the CAR-T cells, the chimeric T-cells are expanded, and then shipped back to the treating center where the cells are infused intravenously to the patient. There is already an approval of CAR-T cell therapy for diffuse large B-cell lymphoma as I mentioned. It is now approved CAR-T called axicabtagene ciloleucel or axi-cel is approved for mantle cell lymphoma, and what we heard at this in Boston. She gave an update on treatment of relapsed refractory follicular lymphoma and marginal zone lymphoma with the axi-cel CAR-T.

So what Dr. Jacobson and her colleagues reported was for patients with relapsed and refractory follicular lymphoma, the overall response rate was 95%, with 80% of these patients being in a complete remission with ongoing follow-up. In those with marginal zone lymphoma, the numbers of patients treated were smaller, but they also showed high-response rates, 85% with 60% achieving a complete remission. And at a year of follow-up, most patients were remaining without evidence of disease progression. So a very promising advance in follicular lymphoma. It also raises the possibility that we may be able to use CAR-T cell therapy instead of traditional autologous stem cell transplantation for relapsing patients.

But this is something that will have to be tested in formal clinical trials before becoming established as a new standard of care. So by the end of the meeting, it was clear that progress continues at a very rapid pace across the fields of human logic malignancies, lymphomas, leukemias, multiple myeloma, and others. So it reminds us that it's important if you're dealing with 1 of these disorders that you make sure you've done your due diligence in getting another opinion if that's warranted, at seeking out clinical trials which help bring some of these most promising therapies to the clinic and help us advance the progress in treatment as rapidly as possible. So I'd like to thank you for your attention today and wish you all the very best in the year ahead.

ASCO: Thank you, Dr. Williams.  You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.  

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today's podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer.

This podcast will be led by Dr. Timothy Gilligan, Dr. Neeraj Agarwal, Dr. Tian Zhang, and Dr. Brian Shuch.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. He has no relevant relationships to disclose.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Janssen and Bristol-Myers Squibb.

Dr. Zhang is an assistant professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Janssen and Bristol-Myers Squibb.

Dr. Shuch is the director of the Kidney Cancer Program at UCLA Health and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb.

View full disclosures for Dr. Gilligan, Dr. Agarwal, Dr. Zhang, and Dr. Shuch  at Cancer.Net.

Dr. Gilligan: Hi, I'm Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute. I'm joined today by Dr. Neeraj Agarwal from the Huntsman Cancer Institute and the University of Utah and Dr. Tian Zhang from the Duke Cancer Institute and Brian Shuch from the UCLA Institute of Urologic Oncology. Today, we're going to discuss 3 ongoing trials in prostate cancer, bladder cancer, and kidney cancer. As you may know, clinical trial are the way that doctors are able to find better treatment for diseases like cancer. Patient participation is vital for clinical trials. By participating in the clinical trial, you can directly help researchers develop better treatment, reduce side effects, and even reduce the risk of cancer altogether. The 3 trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers Panel from the trials in progress abstracts that were presented at ASCO 2020 Genitourinary Cancers Symposium. Because these are ongoing clinical trials, final results from these studies are not yet available. I'd like to note that none of us have any direct involvement in any of these trials. To view our full disclosures, please visit the show notes for this episode on Cancer.Net. We're going to start with Dr. Agarwal and a study looking at prostate cancer, the MAGNITUDE trial. [A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer (MAGNITUDE)] Dr. Agarwal, can you tell us a little bit about this study?

Dr. Agarwal: This is a large phase III trial of 1,000 patients. This trial includes patients who have progressive, metastatic, castrate-resistant prostate cancer and have never received any other systemic therapy for their castrate-resistant prostate cancer.

Dr. Gilligan: Why don't we clarify for listeners what we mean by castrate-resistant prostate cancer? Who are these patients?

Dr. Agarwal: When patients present with advanced prostate cancer which has [spread] to different parts of the body, that is called metastatic prostate cancer. And the most effective strategy, which is the backbone of treatment of these patients, is androgen deprivation therapy or castration therapy, which blocks the production of testosterone from the gonads. At this point of time, utilizing medical castration [with drugs] or surgical castration can effectively slow down the progression of cancer.

Dr. Gilligan: So these are patients who are already on first-line hormonal therapy to lower their testosterone level?

Dr. Agarwal: Yes. Once they start progressing on this first-line castration therapy, we call this state to be castrate-resistant prostate cancer. So this is the patient population which is having disease progression on first-line therapies for the advanced prostate cancer, and now, testosterone levels are low, but still, the prostate cancer is progressing.

Dr. Gilligan: So what's the current standard of care for this population of patients who are progressing on first-line hormonal therapy?

Dr. Agarwal: In the last 2, 3 years, the treatment of castration-sensitive prostate cancer, which is the newly diagnosed advanced prostate cancer we were just talking about, has changed dramatically. Multiple drugs which are being used, or were being used, in the castrate-resistant prostate cancer have moved to the setting of castration-sensitive prostate cancer. Having said that, many patients with castration-resistant prostate cancer have not yet received any of those drugs. So as an example, in this clinical trial, a patient could have received chemotherapy with docetaxel in the first-line therapy setting or a newly-diagnosed metastatic prostate cancer setting. But then when they have disease progression, the most commonly utilized medications are either abiraterone or enzalutamide, both are oral pills, we call them novel hormonal therapies. So those are still the backbone of treatment for castrate-resistant prostate cancer.

Dr. Gilligan: So for patients going on this study, what would the treatment be on the trial?

Dr. Agarwal: Patients will be randomized to treatment with abiraterone, which is a novel hormonal therapy, plus prednisone, which is utilized with abiraterone to negate the side effects of abiraterone, plus/minus a new class of drug known as a PARP inhibitor. And in this trial, the drug which is being used is called niraparib. Niraparib is a novel drug, a PARP inhibitor, and just to elaborate a little bit more on PARP inhibitors, this class of drug have recently been approved [to treat patients with] the later phases of castrate-resistant prostate cancer. So 2 drugs, olaparib and rucaparib, were recently approved by FDA in those patients who have had disease progression on novel hormonal therapy plus/minus docetaxel chemotherapy, so for pretty late phases of prostate cancer or castrate-resistant prostate cancer. In this trial, a PARP inhibitor is being moved upstream so that patients don't have to wait for disease progression or novel hormonal therapy or chemotherapy in metastatic castrate-resistant prostate cancer, and they will have the availability of this drug upfront in this setting of newly diagnosed metastatic castrate-resistant prostate cancer.

Dr. Gilligan: When this drug is used in the more advanced setting, it's limited to patients who have particular mutations. Is that the case in this study as well?

Dr. Agarwal: This trial is targeting the strategy to 2 different patient populations. So 1 patient population is that [in which the] tumor has defects or mutations in the DNA repair genes. We call them homologous recombination repair mutations. I put it simply, DNA repair gene mutations. So there is a cohort of patients, a group of patients, among these 1,000 patients, who will harbor DNA repair gene-related defects in the tumors. And there is another cohort of patients who do not have to have those defects, and we call them unselected patients. This trial is enrolling both groups of patients, and, in fact, the patients' unselected cohort has actually completed accrual. So the trial is now only looking at those patients who are harboring DNA repair gene-related defects in the tumors. Just to complete the story in this context, as you said, the drugs olaparib and rucaparib, which have already been approved in the later phases of castrate-resistant prostate cancer, they are only approved for patients who are harboring DNA repair defects.

Dr. Gilligan: So for the patients who can go on the trial now, who have these defects, the question this trial is asking then is, does it help to use this treatment earlier on rather than waiting until later?

Dr. Agarwal: Absolutely. So given these are oral therapies, reasonably well tolerated, better tolerated than traditional chemotherapies, it makes sense to move these oral pills to upfront or earlier settings where more patients can be candidates for these drugs which can be taken at home, and these patients don't have to have disease progression on chemotherapy to [receive] these medications. Just to complete, Tim, I just want to add that there are 2 endpoints of this trial. One is radiographic progression-free survival, which is the primary endpoint, and the secondary endpoint is overall survival and many other endpoints we'd like to see, like pain progression or toxicities and so on. Radiographic progression-free survival means how long these drugs or drug combination is able to contain the disease from progressing [or worsening] as detected by the scans. We hope that this trial will show delayed progression on the novel combination compared to abiraterone.

Dr. Gilligan: Thank you. So one last question, are there any known risks that patients should be aware of? What are the side effects of this class of medication?

Dr. Agarwal: Yes. Two major side effects. Every drug has side effect. And so do niraparib and abiraterone. So abiraterone is already approved for patients with metastatic castrate-resistant and castration-sensitive prostate cancer. So I'm not going to elaborate much on abiraterone. Regarding niraparib, this class of drug, including olaparib and rucaparib which I earlier mentioned, they have this class of side effects, which belong to this class of drugs. And 1 of the most common side effects is anemia, which is low hemoglobin, and which happens because these drugs can also slow down the replication of red [blood] cells. Other less common side effects are decrease in the platelet counts and decrease in the white cell counts. But they happen with much lesser degree compared to anemia. Another common side effect is nausea. Nausea and vomiting can happen, and we have to keep an eye on nausea and vomiting because the side effect can easily be prevented or treated with anti-nausea medications. There are many other side effects which are less common, and I won't get into them, but these are the 2 most common side effects, which are fortunately easy to handle in the clinic.

Dr. Gilligan: And I just want to repeat what you said before that there is accrual still going on for the study, but it's limited to patients who have particular mutations in their cancers.

Dr. Agarwal: Yes. So currently the study is not accruing for those patients who do not have those DNA repair general-related events. But it is still accruing patients, looking for patients who are known to have those mutations in the prostate cancer.

Dr. Gilligan: What proportion of patients with prostate cancer have these kinds of mutations?

Dr. Agarwal: Depending upon the study, I would say up to 20% of patients can have DNA repair gene-related defects in their tumors. So it is very important to bring this up with our clinical or medical oncologists who are treating patients with metastatic or advanced prostate cancer, and especially with approval of 2 drugs, it is very important that every single patient who is deemed to be a candidate for treatment with this class of drug, PARP inhibitor, undergoes comprehensive genomic profiling or simply speaking, mutation testing of their prostate cancer tumors.

Dr. Gilligan: Thank you. And I think that's worth emphasizing. This is an example of personalized cancer care based on the genomics of the individual's tumor which is happening more and more, and as Dr. Agarwal said, if you have metastatic prostate cancer, we are recommending a standard of care that people get genomic testing now. So this is an example of a step in that direction. So thank you, Dr. Agarwal.

Dr. Zhang, why don't we move on and talk about the bladder cancer trial that you were going to discuss, the PROOF 302, that also has a personalized genomic component to it, I believe. [Study of Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations]

Dr. Zhang: In bladder cancer, we've come to a place where the genomic profiling is very important to find FGFR mutations or fusions, and this subset of patients that have FGFR mutations or fusions, these patients tend to have good responses to now standard of care treatments in the metastatic setting. And this particular trial is looking at using a drug called infigratinib in this patient population, specifically targeting that FGFR and inhibiting it. This is a trial in the adjuvant setting for patients who have urothelial cancer of either the bladder or of the ureters and upper tract who received surgery and then go onto this trial or treatment with infigratinib versus a placebo.

Dr. Gilligan: Can you spell out for our listeners who the group of patients are who are going to be eligible for the study?

Dr. Zhang: Sure. These are patients who have already undergone surgery for either their bladder cancer or an upper tract tumor. And so these are patients in that 4-month window after surgery, who have already had their surgeries, and it's either for patients who have had prior chemotherapy before their surgeries or not with higher-risk features defined based on each of those populations. But it is for a higher-risk patient population that have a higher risk for having disease recurrence and spread of their urothelial cancers after surgery. In this setting, we really don't have any approved adjuvant treatments. And so the point of this study is really to try to prevent disease recurrence.

Dr. Gilligan: I want to clarify 1 thing. My understanding was for these patients who have not had preoperative chemotherapy, they are not patients who were considered eligible for postoperative cisplatin-based chemotherapy since that is often used in the adjuvant setting. Is that correct?

Dr. Zhang: That's absolutely correct, Tim, and thanks for pointing that out. So if patients had not received preoperative chemotherapy, they have to be ineligible for cisplatin-based chemotherapy, which we would often recommend in the postoperative setting. But if they are not eligible for chemotherapy after surgery and have these higher-risk features, then they would qualify for this study.

Dr. Gilligan: I think it's important for patients to understand that because if considering going on this trial, the standard of care would be just to watch. And so what it's asking is, can we do something instead of just watching that would lower the risk of relapse or worse outcome with the cancer?

Dr. Zhang: Absolutely. I think we always try to recommend proven strategies first, and in this particular case, the recommendation for somebody who is a candidate for chemotherapy after surgery would still be to go with chemo first.

Dr. Gilligan: The genetic testing that will be done to determine eligibility for the study, can you say a little bit more about that?

Dr. Zhang: Sure. My understanding is that the study will take most genomic tests that are currently commercially available, but they have to fulfill the criteria of having FGFR mutations and/or fusions in the tumor in order to go on the study. So we often now will send the surgical specimens for genomic testing, especially in our higher-risk patients that are defined like the study defines. And so that particular patient population, because they're at higher risk for recurrence, we try to identify these FGFR mutations and fusions early on so that we can know whether the standard treatment for these patients would be an option later on.

Dr. Gilligan: Are there cost implications of that for the patients?

Dr. Zhang: Certainly, now some of the commercially available genomic testings are approved by insurance and are billable through insurance, but patients may be responsible for a copay. I want to add 1 more thing about the drug itself because I do think there's some interesting activity of infigratinib that has been published in the last year, and that is in the earlier-phase studies of infigratinib in the metastatic setting, in the more advanced urothelial cancer settings, we saw pretty high response rates as well as disease control rates, particularly in patients who had disease in the upper tracts, so in the ureters and above. And so I think it's promising and potentially very interesting to study this for patients who have had disease removal, and surgeries.

Dr. Gilligan: That's an important point for listeners to understand, that this is an exciting new class of drugs and in patients for whom this treatment is appropriate, we're seeing very good response rates in more advanced disease settings, and there's a natural progression. When we see it work in the advanced setting, we try to move it to an earlier setting to see if we see a similar or greater benefit. As Dr. Agarwal was saying about prostate cancer, we've found a number of times that using drugs earlier works better. This is another example of studying that to see if that's the case here.

Dr. Zhang: I absolutely agree.

Dr. Gilligan: What should listeners know about potential risks or side effects for this class of treatment?

Dr. Zhang: FGFR inhibitors like infigratinib have a class effect, and I think the main toxicities that we've come to see are skin toxicities and nail toxicities, as well as there are some eye toxicities as well. So particularly for patients who are going on these types of treatments, we often will recommend baseline eye exams, and then to follow them on treatment, particularly for any blurry vision or other vision changes that arise. And 1 of the class effects of these FGFR inhibitors is also to cause increases in phosphorus levels [in the blood], and that is due to their inhibition in the renal tubules to prevent phosphorus excretion. And so there was a recent publication also that for patients who develop high phosphorus levels, while getting infigratinib or these FGFR inhibitors, that these patients actually have potentially a higher response rate as well. So I think that has to be proven more in these bigger trials, but it's an interesting biomarker potentially for patients who might have good responses.

Dr. Gilligan: So for patients who had urothelial cancer resected or at high risk for relapse, this is an exciting new option for them, if they have the right genomic composition of the cancer and would not otherwise receive chemotherapy. So thank you for the summary.

Okay. So now we're going to talk about kidney cancer and the CYTOSHRINK discussion. [SBRT With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer (CYTOSHRINK)] And we have Dr. Brian Shuch with us to discuss that. Brian, can we start off with who this study is designed for?

Dr. Shuch: It's really designed for patients with metastatic kidney cancer. Could be any type of kidney cancer, presenting with metastatic disease. We call that de novo metastatic disease. So they would have their primary tumor still in place in their kidney, with disease outside of that organ in other locations.

Dr. Gilligan: So these are patients with-- they have the tumor in their kidney, it's spread somewhere else, and they haven't had any other treatment so far? They haven't had any surgery or any drugs?

Dr. Shuch: Correct. These will be patients that are treatment-naïve that are going to start on their first course of treatment, which, in general, would be a discussion of either surgery or systemic therapy.

Dr. Gilligan: So at this point in time, what's the standard of care for such patients?

Dr. Shuch: We used to take every patient to surgery upfront. We call that a cytoreductive nephrectomy. Since we've had much better agents in recent years, and these agents have a lot of activity, we've done less upfront surgery as it appears that some patients may not benefit from racing off to the OR. So these are patients that generally would get started on systemic therapy first because this population, and this trial, has some risk factors for worse disease. We call that intermediate- or poor-risk features.

Dr. Gilligan: So these are patients who we would not normally do surgery on because it doesn't seem to help them, unlike some of the other patients who we do, the good-risk patients.

Dr. Shuch: Well, we are investigating that in other trials, but there are plenty of patients who are not going to run right to surgery, and these are the ones that we would consider deferring surgical management of the primary tumor. We would get started on systemic therapy, and we would reassess how they would be [treated] in the future, whether surgery was an option. But there are emerging entities such as radiation, which we'll discuss, which could be another exciting approach.

Dr. Gilligan: So if a patient that was going to go on this trial didn't go on the trial, they would most likely be treated with medications at this point in time. Is that correct?

Dr. Shuch: Correct. There'd be standard medications which are available off clinical trial which are right now dual therapy with 2 immune agents, or an immune agent and a tyrosine kinase inhibitor. So these are standard drugs that are available off a trial. Patients get started on therapy, and we see how they do later for other treatment options.

Dr. Gilligan: So what is this study looking at? What's the new thing that it's introducing and the question that it's asking?

Dr. Shuch: So kidney cancer, 10, 15 years ago, there was never really any role for radiation except for very rare circumstances. But now we have newer types of radiation where we're doing radiation at much higher doses in shorter time periods, and we call that ablative dosing. And as we've used that in brain and bone lesions for kidney tumors, and with excellent efficacy, with great—what we call local control. That has been applied to the primary tumor as well, and that's been used in many fields, that type of alternative radiation approach. We call that stereotactic radiation or the term radiosurgery, which is really a misnomer. It's just high dose ablative radiation, and it can be used in the primary tumor as a way maybe to kill the tumor.

Dr. Gilligan: And what is that outcome that we're hoping for? How would success be measured if this trial is positive?

Dr. Shuch: Well, we do know for small tumors, it seems to be a fairly effective measure at stopping tumors from growing. In this situation, it's employed after initiation of systemic therapy. Half the patients will get this radiation therapy to that primary kidney tumor, and the goal is to see if it delays progression of the disease. What we call progression is generally growth of lesions that are existing, or development of new lesions, new spots around the body. So the goal is to see if radiation with the standard immune therapy would delay progression versus the standard immune therapy alone.

Dr. Gilligan: So just to reiterate then, I guess for patients who are on this trial, normally they would get treated just with the immunotherapy or combined immunotherapy and targeted therapy, and what we're asking here is, if we give them radiation too, do they do better? Do we delay progression of disease? That we keep things under control longer, that they live longer?

Dr. Shuch: Correct. Obviously, living longer is a major factor. That's another objective of the study, but the study doesn't have enough patients or enough power to kind of detect that. The real issue is, does it delay the progression? And progression is important because if you have progression, often patients will progress to another line of therapy, meaning disease is not under good control.

Dr. Gilligan: Are there any known risks from the radiation therapy the patient should be aware of?

Dr. Shuch: Depending on the size of the tumor and the location to other organs, radiation could have some local effects. Obviously, there's some potential damage to surrounding structures such as the skin. There's some radiation that potentially could stray into other surrounding organs like the duodenum on the right side or the liver, the colon, small bowel, the ureter. And those organs generally can have some degree of toxicity. Generally, it's self-limiting with minor long-term effects, but we haven't done this for many, many years because it's a newer emerging modality. We do believe it's safe with large studies of smaller tumors, but patients do need to be aware that there could be some local irritation from radiation.

Dr. Gilligan: Is this trial still open to patients?

Dr. Shuch: So this is a trial based out of Canada by 1 of their cooperative groups in Ontario. It's a small study - only 78 patients - that opened this year. In discussion with the investigators, this study is accruing well, but it is anticipated to be open for another year. Because they're looking at what's called progression-free survival, we're hoping we can have results of this study within the next 2 years. Obviously, it is something open only to Canadian residents right now, but I will tell you that there are other groups in the U.S. that are considering similar types of trials in the Cooperative Group Network.

Dr. Gilligan: There's 1 final point I wanted to give you an opportunity to clarify for our listeners who may not be familiar with the idea of cytoreductive nephrectomy or cytoreductive treatment. So this is a treatment where we are targeting the primary tumor, even though there's other cancer elsewhere in the body that we can't remove. Can you just talk a little bit about the rationale for that, and why we're doing that?

Dr. Shuch: Historically in kidney cancer, when we had no effective therapy, we would have this phenomena: we removed the big bulky tumor, and 1% to 2% of patients would have their distant sites shrink, okay? And whether that was related to an immunologic phenomenon, maybe the tumor was secreting something, or maybe it was just overwhelming the body's defense mechanisms because they had a big tumor making them sick, it was kind of unclear. But we did know in larger trials with immune therapy, when we gave immune therapy in the old days, the agents like interferon-alpha or IL-2, we gave these agents, the primary tumor wouldn't shrink. Sometimes the distant sites could shrink, but it would not lead to what we call complete responses. So anyone who wanted to have a home run therapy where it was hoping to cure them, they would have their primary tumor removed first, and then they would potentially have the systemic immunotherapy. We've done 2 trials which showed, early in the 90s, that if you were able to remove the primary tumor and treat with these older immune agents, patients would have better outcome. And as those agents were pretty ineffective, we thought the survival benefit was really due to removing the big bulky primary. So the rationale for this trial is, you're not removing the big bulky primary tumor, you're potentially killing it with radiation, so you're overall reducing the burden of disease. There are some theoretical benefits of radiation where you kill tumors, and the tumors release what we call antigens. Basically, I try to explain that to people it's basically like a patch. Like a Boy Scout or Girl Scout has a new patch on them, and you'd recognize them as maybe having a badge of like hunting. So the tumor potentially might expose some of these bad patches, and the immune system might wake up and recognize them, and hopefully, then attack other sites of disease. So, again, the goal is either you're reducing the overall burden of disease in the body, or you're maybe allowing the body's immune system to kick in because you're killing a [tumor] there. We're just not sure really the mechanism, but it's been long used in kidney cancer, this idea of reducing the burden of disease.

Dr. Gilligan: Thank you for listening to this podcast. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team.

ASCO: Thank you, Drs. Gilligan, Agarwal, Zhang, and Shuch.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Cancer does not affect all people equally. Some groups of people, including racial and ethnic minorities, poor people, sexual and gender minorities (LGBT+ people), adolescent and young adult populations, and older adults, are more likely to be diagnosed with cancer, or have poorer outcomes.

This is known as "health disparities." In today's podcast, Dr. Petros Grivas and Dr. Edith Mitchell discuss health disparities in cancer clinical trials, why it is important for clinical trials to be inclusive, and resources for people with cancer who face barriers to care.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine, and an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. He is also a Cancer.Net Specialty Editor.

Dr. Mitchell is Clinical Professor of Medicine and Medical Oncology at Jefferson Medical College of Thomas Jefferson University, and the Director of the Center to Eliminate Cancer Disparities at the Sidney Kimmel Cancer Center at Thomas Jefferson University.

View disclosures for Dr. Grivas and Dr. Mitchell at Cancer.Net.

ASCO would like to thank Dr. Grivas and Dr. Mitchell for discussing this topic.

Dr. Grivas: Hello. This is Petros Grivas. I'm a medical oncologist at Seattle Cancer Care Alliance. I'm an associate professor at University of Washington and associate member of the Fred Hutchinson Cancer Research Center. I'm real delighted today to be able to discuss with a legend in the field, Prof. Dr. Edith Mitchell. Dr. Mitchell is well-known internationally for her work in oncology as well as health care disparities. Dr. Mitchell is directing the Diversity Services features of the Sidney Kimmel Comprehensive Cancer Center, and is a full Professor there, she is a medical oncologist, as I mentioned. And in addition to many achievements that she has over the years, and her international role in cancer research education and patient care, a few examples of her achievements include that she has been selected to be a member of the President's Cancer Panel and also in the NIH Council of Councils, which speaks highly of her contributions in the field. And I was impressed to find out recently that she was the first woman physician that was promoted to the rank of general in the U.S. Air Force. And again, there're many other accomplishments. Dr. Mitchell and myself have no relevant disclosures in relation to this particular topic that we're discussing today.  Dr. Mitchell, thanks for joining us today.

Dr. Mitchell: Well, thank you so much, Dr. Grivas. It's really good to speak with you again, Dr. Grivas.  And thank you so much for the opportunity to discuss disparities with you today.

Dr. Grivas: Absolutely. And thank you so much, Dr. Mitchell, for your nice words. We talked a bit about health care disparities. And your work in the field is really, really important. Could you comment a little bit about health care disparities—the definition—and what we mean when we talk about that?

Dr. Mitchell: Sure. So when we speak about disparities, it's very important that we understand that for any disease process, whether it's a cancer disease or some other disease, if there are differences among communities, either in the incidence rates, that is, how often the disease or the problem occurs, as well as how often there are deaths. So mortality rates being different in different individuals. Could be men versus women, or Blacks versus Caucasians, or Latinx or other racial or ethnic, or differences even between the South and the North. There are a number of disparities that are different and occur more frequently in individuals who live in the southern part of the country. So disparities meaning that there are differences either in the number of occurrences or incidence rates or in the number of deaths, mortality rates, in different communities and among either a racial or ethnic groups or among people. For example, young patients versus older patients. So evaluating differences that occur among people because of their community.

Dr. Grivas: Thank you, Dr. Mitchell. This is very, very helpful to understand. You mentioned some very good examples. Can you elaborate a little bit further about who are the most negatively affected by this, in your opinion?

Dr. Mitchell: So it's well-recognized that men have higher death rates from certain cancers. It's also recognized that for the number of individuals that we've collected information about over the years, that African Americans have higher incidence rates of certain cancers and higher mortality rates of others. It's also recognized that African American men have the highest death rates and highest cancer occurrence rates or incidence rates of any group in the United States. So there are a lot of research ongoing now, evaluating men, and particularly African American men, to find out why there is a higher incidence rate and a higher death or mortality rate in this country. So lots of research.

There is also a lot of information that over many years, cancer incidence rates have been higher in Blacks compared to whites among males and in whites compared to Blacks among females. So while Caucasian women have higher incidence rates, the African American women have higher death or mortality rates. Also, we have evaluated cancer mortality rates in many different populations and it's still the fact that African American men as well as African American women have higher mortality rates compared to whites. So very important that research continues with those.

And for a few cancers, for example, prostate cancer in men, African American men have higher incidence rates of prostate cancer as well as higher death rates. Breast cancer, another area. African American women have higher death rates from breast cancer, although the incidence rates are approximately equal. African American women have more aggressive tumors and more of triple-negative tumors. And triple-negative breast cancer tumors are more aggressive tumors. They spread more rapidly, there are fewer medications to treat the cancers with, and consequently, overall death rate's higher in Black women compared to Caucasian women. Colorectal cancer, another where there are higher incidence rates, with African Americans having a 20% higher incidence rate of colorectal cancer in this country and African Americans having a 40% higher mortality or death rate in this country from colorectal cancer.

And then the last that I will mention-- now, I could go on and on with different cancers, but multiple myeloma. Multiple myeloma is probably the most disparate cancer of all of those in the United States. The incidence rate of myeloma in African Americans is twice that of Caucasian patients, and the death rate being even higher than twice as many. So there are so many different-- and consequently, it's important for clinical trials for us to-- understand everything from the preventive strategies and trying to prevent cancer in various populations through early detection and trying to find the cancers at an earlier stage. And the earlier we find the cancer, the better the treatment outcomes and better opportunities for a cancer cure. So really important.

And then, of course, there're the diagnostic studies. Treatments can be different in patients and consequently, finding the right treatment for the right patient at the right time being important. Also, we do research and clinical trials regarding posttreatment, quality of care, and survivorship. So really important for individuals to participate in clinical trials so that the patient can have access to and the opportunity to receive the latest information on treatment for this specific cancer as well as follow-up diagnostic studies, the specific scans, or other markers. 

There, actually, Dr. Grivas, is a study ongoing where individuals may participate in a study even before they develop cancers or chronic diseases. And that's called the All of Us study. With All of Us, it is planned that approximately 1 million participants will be invited to participate in this trial, and information regarding a specific participant or a specific individual can be given back to the patient or the individual. Like I said, many individuals will not have developed a cancer or a chronic disease. And this might help individuals determine what the risk factors are for developing certain tumors over a period of time. So All of Us is another study by the NIH that will help determine risk factors for patients. So I think for every patient to try and find out information, 1, regarding the tumor if they have developed a cancer but, 2, determine screening strategies to try and find the tumor at an earlier stage and then opportunities for participation in prevention trials to try and prevent cancers from forming. So lots of different clinical trials ongoing and very important for specific populations.

It's well-recognized that African Americans have higher incidence and mortality rates. Latinx or Hispanic patients, there are some tumors that have higher incidence or higher death rates. And the Native Americans also, for certain tumors, have higher incidence rates and higher death rates. So so much in terms of clinical trials ongoing and especially for minority populations. Finding out information about a clinical trial and the opportunity for participating in a clinical trial, very important.

Dr. Grivas: These are excellent points, Dr. Mitchell. I want to ask you to comment a little bit on the efforts overall and your role in National Cancer Institute and other forums. What is the oncology community's trying to do to reduce these disparities? You mentioned clinical trials as a main important topic. But what resources are available to the patients in order to try to avoid those barriers and enroll in clinical trials and eliminate disparities in patient care?

Dr. Mitchell: Certainly. And that's a great question because individuals can, if there is access to the internet, go into clinicaltrials.gov. One can find information about trials as well as potentials for treatment trials and just basic information about the disease process. So if there is breast cancer, you can type in "breast cancer," and you'll get the information on breast cancer or any specific cancer. And I urge patients not to just go to the internet and look for things but go to the NIH or the NCI websites. Those are the areas where the greatest research has occurred, and this is research that is specifically targeted for the United States population. So we do provide that information. We also provide information that patients can give to their physicians and ask questions. Always ask questions to your physicians or other clinical staff. The nurses are great resources of clinical information. It's always good to ask those questions.

And if you use the internet, go to clinicaltrials.gov, and you will get the latest in terms of the National Cancer Institute studies. But you can also get information regarding the disease processes. And another good site is that of the American Cancer Society, which also has outstanding patient information that is reliable and trustworthy. So I usually recommend those 2 sites, but there are others. And especially if there is a National Cancer Institute-designated cancer center in the area. These are funded by the Congress and therefore are excellent areas for information as well as treatment. So I do recommend that patients utilize these resources instead of routinely just clicking on the disease process and seeing whatever comes up on the internet. There are some resources on the internet that are not reliable, that are not clinical trials, and I advise patients to be careful about obtaining information on the internet, and make sure it's from a trustworthy resource.

Dr. Grivas: These are great points, Dr. Mitchell. I appreciate all your work you have done in the field. That's one of the very valuable points for our audience today. I think the take-home message is for our patients and audience participants to ask questions, seek opportunities, make sure they discuss with their treatment providers about clinical trial opportunities for them to be involved in the research and clinical trials. As you mentioned, that's the way to move forward as well as to eliminate disparities in health care. So thank you so much again for your time today and your so-important insights for our audience. Thank you, Dr. Mitchell.

Dr. Mitchell: Oh, thank you so much, Dr. Grivas, and we look forward to working with you on the various projects that we have. And the last thing I'd like to say for patients, that despite the COVID-19 pandemic and the number of patients affected, if 1 has symptoms, then they should still discuss this with their clinicians and go in for cancer screenings, go in for cancer treatment. And if there are questions, talk with your physicians about it. Because although the coronavirus is here, cancer doesn't go away. So we still have to address cancer despite the COVID-19 pandemic, which affects so many Americans. But cancer is not going away. So still talk with your doctors about cancer screening and cancer treatment. Thank you.

Dr. Grivas: Fully agree with you. Great point. Absolutely. And thank you for pointing this out to avoid delays in cancer diagnosis, avoid delays in screening and proper workup. Thank you so much, Dr. Mitchell, for your time today.

ASCO: Thank you, Dr. Grivas and Dr. Mitchell. Learn more about cancer disparities at www.cancer.net/disparities. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Dr. William Dale will discuss new research presented at the International Society of Geriatric Oncology 2020 Annual Meeting, held virtually on October 1st.

Dr. Dale is director of the Center for Cancer and Aging Research at City of Hope, a comprehensive cancer center near Los Angeles. He is also the Cancer.Net Associate Editor for Geriatric Oncology. View Dr. Dale's disclosures at Cancer.Net.

ASCO would like to thank Dr. Dale for discussing this topic.

Dr. Dale: Hello. Welcome to Cancer.Net. Today, I'm going to discuss research highlights presented at the 2020 International Society of Geriatric Oncology, or SIOG, Annual Meeting. I'll be discussing 2 kinds of studies. One, the rapid-fire abstracts, which were the featured abstracts in this year's virtual meeting of SIOG. And at the end, a practice-changing article that was presented. I don't have any disclosures for the rapid-fire abstracts. However, the article that was chosen for hematology to be the most relevant and practice changing this year is 1 in which I participate as a coauthor. But the majority of the work was done by others. And I will describe it when we get to that point in the discussion.    So let's jump right in.

The first study is the qualitative study of a mobile health exercise intervention focused on older adults with myeloid neoplasms. So in this study, a specific intervention from the University of Rochester, a home-based exercise program referred to as GO-EXCAP was applied to older adults to help prevent the decline of physical function and side effects, primarily fatigue, in patients with multiple myeloma. This is a mobile health application which is done in the home and is largely a qualitative study with people over the age of 60. The primary findings were that this intervention was found to be especially helpful for these patients over 60. It was easily applied in the home and could be used for 5 to 30 minutes 2 to 4 times per week. Patients were starting it at the beginning of their chemotherapy. They especially liked the instructions that were provided. Found it very easy to apply and were able to engage with their family and family members during the course of using this intervention. It does involve a web portal and requires a mobile device, so people need to have those. But the activity tracker that was used, which is a common one, was provided by the team. It looks like a very promising potential intervention, knowing how important exercise is, with some caveats on the use of technology for older patients.

Another study, a second study, is on the feasibility of doing a pragmatic geriatric assessment in a low-resource country, which is Brazil. So the goal of this study was not just to apply the geriatric assessment, which is known to be of importance for any older adult 65 and above with cancer, but to make it very practical and for use in an environment where you don't have all the resources you would have in an academic setting. So prior to an initial consultation, a nurse would apply the pragmatic geriatric assessment that included some very straightforward tests, ones that are recommended through the ASCO guidelines in 2018 and the SIOG guidelines that just came out. This was gait, speed test, a four-meter walk, a polypharmacy questionnaire, a mini nutritional assessment, a geriatric depression scale with 5 questions, and a mini COG, which is a small cognitive assessment for a few moments. They did this in a population of patients whose average age was 73 years old with a range from 61 to 93. And a number of findings. 39% of people were fit, but 22% were frail. With the rest, about 40%, in the prefrail state. A large majority, over 50%, were experiencing polypharmacy. 23% had depression. And 42% had concerns about cognitive impairments. We are able to show that even in a low-resource environment where it's typically difficult to apply a geriatric assessment  this pragmatic assessment was able to be conducted, completed, and the major domains of a geriatric assessment were instigated. Significant numbers of deficits were found suggesting that interventions for these would be appropriately intervened on. And that would be the next step, is to show that we can use the known interventions to decrease the rates of these concerns.

The next abstract is 1 on the prevalence of geriatric syndromes in community-dwelling older adults. Geriatric syndromes are a common collection of concerns that older adults develop that cluster together and that tend not to happen in younger individuals. A good example is functional impairments, where the inability to do activities around the home is not possible for older adults. Falls is another common one, where multiple contributing causes lead to people falling a common outcome. Also, cognitive impairments among older adults is another geriatric syndrome.  Again, this is an international study in Japan in which over 2,000 people over the age 65 and an average age of 72 were investigated for the prevalence of geriatric syndromes. A number of validated tests were applied to this group of patients and logistic regression was used to find those aspects that were most closely identified with having geriatric syndromes. Over 200 patients, about 10%, had a history of cancer. The prevalence of various outcomes, including physical impairments, depression, and kidney dysfunction, ranged from 4% up to 22%. In particular, the associations of physical impairments was about twofold higher in predicting the presence of a geriatric syndrome. And the community-dwelling older patient survivors had a high prevalence of these syndromes compared to elderly individuals without cancer, making the presence of cancer a concerning marker for the development of geriatric syndromes, even after cancer treatment when people are survivors.

And my last abstract of note was the use of extreme hypofractionation in stereotactic body radiation therapy in older patients with prostate cancer. So 179 patients over the age of 70 who were treated with radiation therapy for clinically localized prostate cancer had the EPIC-26 questionnaire which assesses a range of outcomes at multiple intervals over the next few months to years. And it was found that this extreme hypofractionation, or SBRT, stereotactic body radiation therapy, was very well tolerated in this older adult population with minimal numbers of side effects and led to excellent disease control over the first 3 years of treatment, making it a very well-tolerated and potentially best option for older adults with localized prostate cancer, especially those who have other comorbidities, other geriatric syndromes, and for whom disease control is appropriate. So those were the most important abstracts at the conference.

Next I'm going to move to a hematology study that was cited as the most important and potentially practice-changing published in Blood Advances by lead author Benjamin Derman and senior author Andrew Artz. In this study, a multidisciplinary clinic, guided by geriatric assessments, was used to optimize the care for older adults who are being considered for a hematologic bone marrow transplantation. Patients over 60 years old at a clinic at the University of Chicago had an evaluation of their candidacy for transplantation and then optimization of their care prior to and throughout the transplant process. This multidisciplinary assessment and optimization was conducted through patient surveys, on-site function and cognitive assessments, nutrition optimization, along with the participation of a multidisciplinary team that included PT and OT, a geriatric oncologist, the transplant physician, nutrition, infectious diseases, social work, and then a team discussion following a day evaluation.

This led to important improvements in transplant outcomes. And these outcomes improved over time, likely through a combination of better decision making about who receives the transplantation, those who are most fit going forth. And those who are most frail, perhaps offered other treatment options. This led to decreased deaths during an inpatient stay of transplantation, decreased nursing home admissions, decreased nonrelapse mortality, and increased survival, along with increased quality of life. This approach to older patients, who are now being increasingly considered for transplantation,  does await formal randomized controlled trials to prove this approach is right. This was an observational trial but had quite a few patients and would indicate the value of having geriatric assessment-guided multidisciplinary team interventions.

So there's many other presentations and summaries in various fields at SIOG this year in both solid tumors and hematology, along with geriatrics in general. Please go to the SIOG 2020 website to get all the details and to read about more details from the abstract presentations and to see the presenters on the recordings. Thank you very much. And I look forward to seeing you all online.

ASCO: Thank you, Dr. Dale. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In today's podcast, Dr. Paul Appelbaum, Dr. Allison Magnuson, and Dr. Jonathan Marron, will discuss their article "Medical Decision-Making in Oncology for Patients Lacking Capacity," from the 2020 ASCO Educational Book. They discuss what it means for someone to be unable to make significant medical decisions for themselves, known as "decisional capacity," and offer practical tips for families and caregivers.

Published annually, the Educational Book is a collection of articles written by ASCO Annual Meeting speakers and oncology experts. Each volume highlights the most compelling research and developments across the multidisciplinary fields of oncology.

Dr. Paul Appelbaum is a psychiatrist at Columbia University Medical Center, where he researches decisional capacity and decision-making in medical contexts. Dr. Allison Magnuson is a geriatric oncologist at the University of Rochester, where she researches older adults with cancer and older adults with preexisting cognitive impairments. Dr. Jonathan Marron is a pediatric oncologist, bioethicist, and researcher at the Dana-Farber Cancer Institute and Boston Children's Hospital.

View disclosures for Dr. Appelbaum, Dr. Magnuson, and Dr. Marron at Cancer.Net.

Dr. Marron: Hi. We wanted to welcome you to this Cancer.Net podcast. Today we're going to discuss our article in the 2020 ASCO Educational Book which is entitled "Medical Decision-Making in Oncology for Patients Lacking Capacity." What we hope to focus on today specifically is what this means for patients, for families, for caregivers, and provide some practical guidance not just for oncologists but for patients, families, and caregivers specifically. My name is Jonathan Marron. I am a pediatric oncologist, bioethicist, and researcher at the Dana-Farber Cancer Institute and Boston Children's Hospital.

Dr. Appelbaum: And I'm Paul Appelbaum. I'm a psychiatrist at Columbia University Medical Center where I do research on, among other things, decisional capacity and decision making in medical contexts.

Dr. Magnuson: And I'm Allison Magnuson. I'm a geriatric oncologist at the University of Rochester, and my research focuses in older adults with cancer and more specifically in older adults with preexisting cognitive impairments.

Dr. Marron: We should point out that none of the 3 of us have any relevant conflicts to disclose. Dr. Applebaum, can you tell us a little bit about what capacity is and why it matters to patients and their families?

Dr. Appelbaum: So capacity is both an ethical concept and a legal construct. And it refers to those decision-making abilities that we require people to have, in order to make decisions that are binding decisions, valid and worthy of respect by others. Over the years, this notion of decisional capacity has evolved in a more focused way. So it was once the case that people were considered to be capable of making all decisions or no decisions. And now we recognize that people may be capable of making some decisions but not others. Moreover, we recognize that this capacity taken as a whole can change over time. So if you're sick, in pain, anxious, or of course unconscious, you may lack capacity to make decisions at that point. But the following day, when you are feeling better, no longer in pain, or have consciousness, you'll be quite capable of doing it for yourself.

And then we focus in on 4 components of capacity which is what we look to assess when somebody is concerned that a patient may lack capacity. We ask whether the person can understand the information that's relevant to the decision, can appreciate what that information means for their decision-making context, can reason about the decision in a more or less rational way, and can make a choice and decide whether or not they want a particular treatment or want to be hospitalized or desire a diagnostic procedure. So in a nutshell, that's what we mean by this thing that we call decisional capacity.

Dr. Marron: And so you just mentioned there a couple of different types of decisions that an individual might have to make. Might capacity vary according to each individual decision?

Dr. Appelbaum: Yeah. But capacity is usually thought of as task-specific. So that even within the domain of medical decisions, a very simple decision like should you have a flu shot, like I did last week, is probably not one that requires a great deal of capacity. Indeed, they didn't give me any hard time when I asked for a flu shot. But if you're making a decision that has potentially life-saving or life-changing consequences, whether to accept, for example, or reject potentially life-saving treatment, more capacity may be required. So it depends on the decision that's at hand.

Dr. Marron: So it sounds like as it relates to decisions that an individual with cancer might face, or those who care for individuals with cancer, this could end up being a relatively challenging process. Dr. Magnuson, what are some of the aspects of cancer and cancer care that might affect an individual's ability to have capacity for these kinds of decisions?

Dr. Magnuson: Sure. I think that's a great question. So as Dr. Appelbaum mentioned, certainly the complexity of the decision can come into play. We know that with cancer treatment, some of the treatments that we consider are high risk types of therapies, potentially high benefit but also high risk. And if patients have some type of preexisting cognitive impairment, perhaps some of those more complex decisions may be more challenging and require more support. There are also scenarios with a cancer diagnosis, for example brain metastases, that may impact capacity for certain patients as well.

Dr. Marron: And then back to Dr. Applebaum. So if there's questions about whether or not an individual has capacity, what should patients and family members expect that their clinicians will do in order to assess that?

Dr. Appelbaum: Yeah. I think it's important to say, first of all, that if family members believe that their loved ones may lack capacity, and sometimes they know much better than a doctor or any other member of the medical team who has just met the patient what their baseline functioning is and how different they may look and behave today, that if they suspect that that's something that they ought to communicate to the medical team. If that happens or if the team itself suspects that the person may have some impairment of their decision-making abilities, an assessment will take place. It can be performed by some member of the medical team itself or sometimes it will be done by a consultant. Typically, a consulting psychiatrist who's called in to see the patient and do the evaluation. Unlike blood tests for anemia, let's say, there's no definitive medical test that can be done to determine whether somebody is decisional and capable or not.

The assessment is based on an interview. The interview typically will review what the patient understands about their condition and its nature, the treatment that's been proposed, the risks and benefits, and the alternatives along with their risks and benefits. It will assess whether the patient appreciates their own situation, that is recognizes the nature of their illness and its severity and what the likely consequences of either accepting treatment or refusing treatment might be. It will assess their ability to weigh the risks and benefits and come out with a decision. Typically, a decision that in some way reflects their assessment of those risks and benefits. That sort of interview can take 20 to 30 minutes. It's done at the bedside and the person doing it will integrate that information with information from the family if that's available with a review of the medical chart to see what other problems the person may be having or what variant behaviors or thoughts they may have manifested and will come up with a conclusion.

What's important to underscore as we mentioned earlier is that conclusion is valid for that point in time. If the patient's condition changes, somebody who was competent yesterday may not be today and somebody who lacked that competence yesterday may have recovered it by today, and again if family members are aware of substantial changes in their loved one's condition, that's important to call to the team's attention as well.

Dr. Marron: And that last point that you mention is particularly poignant in my area of practice in pediatrics, since children by definition legally don't have capacity. So we have to think about things in a little bit of a different fashion where typically the child's parents are the ones who are tasked with making decisions on behalf of the child. But we try to integrate the child's voice as best that we can and the age and developmentally appropriate way while understanding that until the age of majority, in most cases an individual doesn't have the legal ability to make a decision for themselves.

That's not to say, however, that just because they can't make a legal decision doesn't mean that they shouldn't have a voice. In your practice, Dr. Magnuson, how do you try to approach patients that don't have capacity or have perhaps waxing and waning capacity?

Dr. Magnuson: Yeah. It's interesting kind of hearing your pediatrics perspective. Because of the area of my interest, many of my patients do come to see me with a new cancer diagnosis and they have preexisting either mild cognitive impairment or dementia. And just as we've been talking about how the complexity of the decision at hand really is an important thing to consider. Often patients may retain the capacity for some of the more straightforward decisions but may need more involvement of caregivers, health care proxy, and such for the more complex, maybe treatment-focused decisions. Thinking through different options, cancer treatment options that have different risk profiles to them. Those are complex decisions and so often how I try to approach it is to really get a sense from patients, as Dr. Applebaum described, what is their understanding about their diagnosis?

Some patients with advanced cognitive impairment may not recall that they have cancer even though they've been to several appointments prior to me where the diagnosis has been discussed. Those are more extreme cases certainly, but kind of getting that level of understanding using a lot of interview techniques in the office visit to gauge people's understanding of the different options that we're talking about. What are the goals and preferences that they're coming to this decision with? Just to get a sense of how are they reasoning through these options and certainly engaging their family and their support. But really emphasizing that they may retain capacity for certain decisions. So we don't want to ignore as you said their voice and their input, even for those more complex decisions.

Often patients I'm seeing are older and they've had many life experiences that have informed their decisions, so their family does come with that knowledge. And so it's important to really kind of evaluate those aspects as well.

Dr. Marron: And with that in mind, is there any advice that you might give to a family member of a patient who will be coming in to the oncology clinic with the expectation that decisions you're going to have to be made, but that the patient him or herself is not thought to have capacity presently? How can families and caregivers help to prepare for meetings like that and decisions like those?

Dr. Magnuson: That's a great question. So sometimes I do see family struggle with kind of really wanting the patient to make the decision themselves. But they're just unable to kind of retain all the detailed information that would go into that decision. And I can see that sometimes be challenging for patients, especially if there's the level of cognitive impairment wasn't maybe previously appreciated to the degree that it's actually present. And so I definitely try to work with patients and families to kind of all be on the same page at kind of where that level of decisional support is needed and try to engage everyone together. I guess as far as advice. certainly as Dr. Appelbaum said, if there's concerns that you as a family member have in this regard sharing that with the team is always helpful and really kind of helps us to make sure that we're assessing at each point kind of that level of understanding.

Dr. Appelbaum: It's probably worth noting that in most cases, unless the patient him or herself has designated another decision maker, it will be the family that the treatment team will turn to to make decisions for an incapable patient. And one of the ways the family can prepare for that in advance is to try to ascertain as early as possible in the process what the patient's desires are, how aggressive they want to be about treatment, how they feel about issues like do not resuscitate orders and other choices that they may have to make, for example, with regard to palliative care or facilities where they may want to be if they get towards the end of their lives.

Dr. Magnuson: Yes, I agree with that Dr. Applebaum. Kind of that ongoing discussion with families about what people's goals and preferences are and they definitely evolve over time, too, I think. So kind of having that open dialogue is important.

Dr. Marron: Seems like a common theme here is how much this can change both for a given individual and then over time and according to different scenarios and different decisions. We certainly see that in the pediatric space as well as children get older and they move through the illness experience, they may develop a greater degree of ability to participate in decisions even if they're still under the age of majority and/or if they get sicker. As Dr. Magnuson mentioned, it's possible that any involvement they had may decrease over time.

Any other pieces of advice that either of you would want to provide to a friend, a family member or a patient who might be coming to clinic and be faced with some of these challenges?

Dr. Appelbaum: So family members are often uncomfortable with their role as decision makers. I know this from my own life, my own experience when I made decisions for my mother at the end of her life and it wasn't easy, and I still think about those choices. But there's general agreement among bioethicists today that the best way to think about these decisions is to try to ascertain what the patient would have done in that circumstance and rather than making a decision for the patient, see yourself as making the decision that the patient would have made if the patient were capable of doing that.

Now sometimes we just have no evidence of what the patient would have wanted, and we have to do the best we can and we make a choice in their best interests. But in so far as we can actually reflect desires, that I think is generally acknowledged to be preferable and is part of the point of those advance discussions that we were talking about a few minutes ago.

Dr. Marron: It's such an interesting and important point because I think that brings up one of the important distinctions in a practical fashion between adults and children and adolescents in this area because children don't have that sort of experience to show parents what they would want. So we have to work as a team to try to integrate both what we feel is in the best interest of the child but also in a way if we can integrating any values or preferences that we're able to elicit from the child or more often the adolescents when making decisions on their behalf.

Well, before we close are there any other additions that are giving you Dr. Appelbaum or you Dr. Magnuson would like to add?

Dr. Appelbaum: I think we've covered the points that [crosstalk] I wanted to make sure we did today [laughter].

Dr. Magnuson: Yes.

Dr. Marron: All right. Well, thank you both and thank you to everybody for joining us with this podcast. Okay. If you're interested in learning more about any of the things that we've talked about today you can visit ASCO.org/edbook. And there you can find the paper that we dive into this in a little bit more depth.

ASCO: Thank you, Dr. Appelbaum, Dr. Magnuson, and Dr. Marron. Please visit ASCO.org/edbook to read the full article. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Dr. Neeraj Agarwal discusses new research in kidney, prostate, and bladder cancer presented at the European Society for Medical Oncology Virtual Congress 2020. This meeting was held virtually September 19-21.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He is also a Specialty Editor for Cancer.Net. View Dr. Agarwal's disclosures at Cancer.Net.

ASCO would like to thank Dr. Agarwal for discussing this topic.

Dr. Agarwal: Hi, my name is Dr. Neeraj Agarwal. I'm a professor of medicine and the director of genitourinary oncology program at the Huntsman Cancer Institute, Salt Lake City, University of Utah. Today, I'm going to talk about 3 major clinical trials which were presented during the 2020 annual meeting of European Society for Medical Oncology. All these 3 trials are practice-changing trials. And they have huge impact on how we treat patients with bladder cancer, prostate cancer, and advanced kidney cancer. Before I proceed further, I want to disclose that I have consulted and received honorarium to the sponsors of all these 3 trials, which include Exelixis, Galentic, AstraZeneca, Pfizer, and EMD Serono. I was also involved in the conduct of the PROfound clinical trial, the trial in prostate cancer which I am going to discuss about, as a steering committee member.

Let's start with the trial in advanced kidney cancer. So this trial was a large phase III trial. It was named as 9ER trial and used a novel combination of cabozantinib plus nivolumab versus sunitinib. Hundreds of patients were randomized to treatment with cabozantinib plus nivolumab versus sunitinib. What we saw was really remarkable. The progression-free survival, which is defined as how long these drugs were able to control the disease from progressing, was remarkably improved with the combination of cabozantinib plus nivolumab versus or over sunitinib. In fact, the progression-free survival was double with the novel combination of cabozantinib with nivolumab versus sunitinib. So if you look at the absolute months, how long the disease was controlled or was contained from progressing, it was 16.6 months with the novel therapy with cabozantinib and nivolumab versus 8 months with sunitinib. In fact, if you look at the progression-free survival estimate as assessed by the treating clinicians who were treating these patients, it was even higher at 19 month versus 9 month.

Overall survival was also improved. We do not have data in absolute months in overall survival, but if you look at the hazard ratios, basically that means that there was a 40% reduction in risk of death on treatment with cabozantinib and nivolumab. Even response rates were twice as high with cabozantinib and nivolumab. The most important aspect I would like to highlight of this trial was the quality of life as reported by the patients. The health-related quality of life in patients who received cabozantinib with nivolumab was consistently better throughout the duration of trial treatment over those patients who received sunitinib. And this speaks of the overall tolerability and safety of the agent. To summarize, the combination of cabozantinib and nivolumab is one of the new standard of care options for our patients and improves survival and quality of life in a very meaningful fashion. Thank you very much for listening to the data of the 9ER trial.

Now I will move on to the prostate cancer trial. The name of the trial in prostate cancer was the PROfound trial. I'd like to bring to your attention that this is the first-ever phase III or large randomized trial which was successful, which was positive, in the realm of metastatic or advanced prostate cancer, where patients were selected based on a biomarker. The biomarker in this context was mutation in the DNA repair gene inside the cancer cells. So truly, it was a very novel trial, with a novel design, and a really new idea in the field of prostate cancer.

So in this trial, around 400 prostate cancer patients or patients with advanced prostate cancer, who were experiencing disease progression on novel hormonal therapy such as abiraterone or enzalutamide, and they could have received chemotherapy as well, were randomized to treatment with olaparib, a PARP inhibitor which targets those cells which harbor the DNA repair mutations or DNA repair gene mutations. So patients were randomized to treatment with either olaparib or the other novel hormonal therapy which they had not received before, which were enzalutamide or abiraterone. The patients were divided into 2 different cohorts. The first cohort had patients with BRCA1, BRCA2, and ATM gene mutations. The second cohort included patients with 12 other different types of mutations, also in the DNA repair gene. Again, what we saw was really striking. Treatment with olaparib resulted in delaying of disease progression as well as a significant increase in the overall survival. Overall survival was improved in these patients by almost 4 and half months on treatment with olaparib. If we look at the median overall survival in patients who did not get olaparib and who were on enzalutamide or abiraterone, the median overall survival was 14 and a half months. And that had improved by almost 5 months in patients who received olaparib. It basically translates into 30% reduction in risk of death.

I would like to bring to your attention, is that almost two-thirds of patients on this trial who received abiraterone or enzalutamide were allowed to cross over to novel therapy with olaparib during the conduct of the trial when they had disease progression on enzalutamide or abiraterone. So when you factor in this crossover— because whenever you see crossover, it always leads to attenuation or a decrease or apparent diminution of the survival benefit. If you account for the crossover of those two-thirds patients from control arm to the olaparib arm, the median overall survival was even further improved with almost a 60% reduction in risk of death. The side effects with olaparib—  there are 2 main side effects which I would like to mention. One is nausea, and 1 is anemia, which really differentiated olaparib from the alternative enzalutamide or abiraterone. And these 2 side effects are easily manageable in the clinic. So based on these data, olaparib was approved by FDA and now is available in the clinic.

I think the biggest challenge for us is to identify those patients who are candidates for treatment with olaparib. So any time a patient sees a doctor, a patient with advanced prostate cancer sees a doctor, it is extremely important that the discussion about genomic testing is brought up. Genomic testing of the tumor, genomic testing of the tumor tissue, as well as the circulating tumor DNA coming from the tumor, which is floating in the bloodstream, and referral to a germline testing clinic. Because many of these mutations are heritable and they can result in familial predisposition of other cancers.

So, to summarize, PROfound trial in advanced prostate cancer patients for the first time showed that patients can be selected for a targeted therapy based on underlying mutation in the DNA repair gene in their prostate cancer cells. And if they have these mutations, they are candidates for treatment with olaparib. There's another drug which also got approved in a very similar setting in patients who have already received chemotherapy, is rucaparib. So there are 2 drugs now which are approved in this setting for the patients who are harboring these DNA repair gene-related mutations.

So the final message which comes from the PROfound trial is a very important one. Every patient with advanced prostate cancer has to be tested for the presence of these mutations in their DNA repair genes in their tumors. And this mutation testing can be done by testing of the tumor tissue or by a simple blood test which looks at the circulating tumor DNA coming from the tumor tissue which is floating in the bloodstream. And of course, all patients need referral to a high-risk genetics clinic to be assessed for the hereditary component of these mutations to make sure they're not carrying these mutations in their germline DNA, which may potentially result in hereditary or inheritable nature of this mutation.

Now I'd like to talk about the main trial which has already changed practice in patients with advanced or metastatic bladder cancer.

The name of the trial is JAVELIN Bladder 100 trial. The earlier data was presented in the 2020 Annual Meeting of American Society of Clinical Oncology. And more data was presented in 2020 Annual Meeting of European Society for Medical Oncology. In the JAVELIN Bladder 100 trial, hundreds of patients with advanced or metastatic bladder cancer, who were receiving treatment with first-line chemotherapy with cisplatin or carboplatin and had received at least 4 to 6 cycles of these chemotherapies and did not have any evidence of disease progression, so they could be responding or they could have had stable disease - they had to have stable or responding disease - were randomized to treatment with avelumab versus best supportive care, meaning they were just watched carefully by the doctors, which is the current standard of care. So these patients who have stable disease or responsive disease after 4 to 6 cycles of platinum-based chemotherapy, they're watched carefully. So this was done in this trial for those patients who were on the best supportive care arm. And half of the patients received--in addition to periodic scans, they received treatment with an immunotherapy known as avelumab.

Again, what we saw was really striking. The overall survival was clinically and significantly improved in patients who received avelumab. The improvement in overall survival with avelumab was approximately 7 months. So 14 months in patients who did not receive avelumab and 21 months in patients who received avelumab. This translates into 30% reduction in risk of death in those patients who received avelumab. Please note that the benefit with avelumab was present in every subset of patients in this trial. It didn't really matter where the disease was present, whether it was present in the viscera versus only lymph nodes, whether tumors were expressing a certain biomarker known as PD-L. Every group of patients responded to avelumab.

The side effects of avelumab are not new to the patient and physician community. This drug has been approved in the later lines of bladder cancer treatment for almost 2 years now. Most of the side effects which happen are really easily manageable. And in less than 3 to 4% of patients, side effects can be more severe. We call them grade 3 and 4 side effects. And basically, they manifest as diarrhea, skin rash, liver function abnormalities. And for these reasons, patients who are receiving avelumab, they need to be followed by their oncologist at least on a monthly basis.

Having said that, I think these data are wonderful news to our patients. In fact, we have never seen such magnitude of overall survival improvement in patients with advanced or metastatic bladder cancer in this setting ever. Thank you very much for listening to me regarding the data of the JAVELIN Bladder 100 trial.

ASCO: Thank you, Dr. Agarwal.

You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, "What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?" In this final episode of 2020, editors discuss new research in the fields of central nervous system tumors and lymphoma.

First, Dr. Glenn Lesser will discuss new research on a form of non-Hodgkin lymphoma that begins in the central nervous system, and research into a possible treatment for breast cancer that has spread to the brain. Dr. Lesser is the Louise McMichael Miracle Professor and Associate Chief in the section on Hematology and Oncology in the Department of Internal Medicine at Wake Forest University, with joint appointments in the Departments of Anesthesiology, Neurosurgery, and Public Health Sciences. He is also the Cancer.Net Associate Editor for Central Nervous System Tumors.

View Dr. Lesser's disclosures at Cancer.Net.

Dr. Lesser: Hello. My name is Glenn Lesser, and I'm a professor of medical oncology and director of medical neuro-oncology at the Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina. I'm also the editor of the brain tumor section for ASCO's Cancer.Net. And today, I would like to briefly discuss what I think are 2 of the most clinically relevant research studies on brain tumors that were presented at this year's ASCO's Virtual Scientific Program. I should say right up front I have no disclosures or relationships that are relevant to the particular studies I'll be discussing today.

Unlike the progress we've seen in the treatment of many cancers over the past few years, patients with brain tumors and the physicians who care for them have not seen the same rapid advance in effective treatment strategies. Cancer that begins in the brain, so-called primary brain tumors, and the more common situation of cancer that spreads to the brain after originating elsewhere in the body, so-called metastatic or secondary brain tumors, still have relatively few effective treatment options available. However, I believe that the 2 abstracts we'll discuss today may impact the way that we treat certain primary and metastatic brain tumors in the future.

The first study I'd like to talk about was presented by Dr. Omuro on behalf of a group of international colleagues that described a randomized study of standard chemotherapy with or without low dose whole brain radiation in patients with a brain tumor known as a primary central nervous system lymphoma, which I may also talk about as a PCNSL for abbreviation. Non-Hodgkin's lymphoma is a relatively common cancer that involves the blood and lymph nodes throughout the body. Primary central nervous system lymphoma is the term used when patients develop a non-Hodgkin's lymphoma that's confined to the central nervous system which is really made up of the brain, the spinal cord, the spinal nerves, and the spinal fluid. This turns out to be a pretty rare diagnosis with only about 1,500 new cases of this cancer occurring in this country each year. This type of lymphoma is important, though, because it's very treatable in most patients, and a significant percentage of our patients can be cured with appropriate therapy. Because the disease is so rare, we really don't have the results of large clinical trials to help us determine the best treatment approach for patients with primary central nervous system lymphoma. And as a result, there are a variety of controversies over how to initially treat patients who develop this lymphoma, so-called induction therapy, as well as what type of treatment to give once the disease has been made to go away, or so-called consolidation therapy. In the past, radiation therapy to the whole brain was used to treat patients with PCNSL. And most of these patients who were treated with radiation-containing regimens had their tumors respond, although the cancer frequently returned within a year or 2. This approach has really fallen out of favor over the last few decades because of the very high incidence of neurotoxicity or brain damage from the radiation that was seen in surviving patients.

Unfortunately, a significant number of those patients who were treated with high doses of whole-brain radiation therapy developed a progressive irreversible dementia over the years following the radiation treatments, and a particularly high incidence of this toxicity was seen in patients who are over the age of 50. With current multi-agent chemotherapy regimens, a high percentage of treated patients are having their lymphomas go away. Unfortunately, a significant number of patients still have their disease come back within months or years of this treatment. And so strategies to consolidate or lock in that initial good result with treatment are being evaluated. These strategies may involve high doses of different types of chemotherapies, consideration of bone marrow or stem cell transplant, and even long-term maintenance treatment with oral chemotherapies. More recently, low doses of whole-brain radiation therapy have been explored as a way to try to prevent these lymphomas from coming back with a thought that the low doses of radiation might have minimal long-term brain toxicity as compared to the high doses of radiation given in the past.

So this study that was presented at ASCO involved about 91 patients with primary central nervous system lymphoma. Half of them received the low-dose whole-brain radiation therapy after their tumors were treated with several months of multi-agent chemotherapy, while the other half did not get the radiation. After a follow-up period of 4 to 5 years, the results of this treatment were that the patients who received the low-dose radiation in addition to chemotherapy lived longer and had a significantly higher rate of their tumor going away and staying away at least at the 2-year follow-up tie point. Now, data is not yet available on the neurocognitive outcomes in both groups of patients. That is how well their brains were functioning with tasks like memory, calculations, and personality. The improved results seen in this group of patients who got radiation suggests that this approach may be one effective way of helping to consolidate the treatment of primary central nervous system lymphoma after the induction chemotherapy.

These results, however, can only really be fully interpreted and applied once we have more long-term information on whether the patients treated in this fashion suffer from the high rate of neurotoxicity and dementia that was seen in prior studies using the higher doses of radiation. With further follow-up, this study should provide us with some definitive information on whether the strategy of adding low-dose radiation following standard induction chemotherapy is a good one for patients with primary central nervous system lymphoma.

The second study I'd like to talk about was presented by Dr. Nancy Lin, again on behalf of an international group of colleagues, and described the results of a trial adding a new drug called tucatinib to a standard chemotherapy regimen of trastuzumab and capecitabine in women with HER2-positive breast cancer involving the brain. Now, many common cancers have a tendency to spread to the brain if they recur after initial treatment. This metastatic or secondary involvement of the brain occurs in over 200,000 patients a year in the U.S., and new treatments for brain metastases are desperately needed. Women with advanced breast cancer are particularly susceptible to developing brain metastases, particularly if they have the subtype of breast cancer known as HER2-positive disease. In HER2-positive disease is defined that way because of the presence of the HER2 protein on the surface of breast cancer cells. Although a number of effective treatments have been developed for patients with HER2-positive breast cancer involving the body, including some common drugs like trastuzumab and pertuzumab, these agents have not been particularly effective in either treating breast cancer that has spread to the brain or preventing the breast cancer from spreading to the brain in the first place.

One of the main reasons why these chemotherapy drugs have not been effective in treating breast cancer metastases in the brain is that unlike the other organs in our bodies, the blood vessels of the brain are formed in such a way that they carefully restrict what substances in the blood are able to leave the blood and spread into the brain. Normal blood vessels in our body are somewhat leaky. And fluids, proteins, drugs can leak out of those vessels into the tissue with some freedom. The blood vessels of the brain, however, are lined by cells that tightly joined together to create a blood-brain barrier that is not leaky, and that barrier protects the brain from compounds that are circulating in our bloodstream which could adversely affect brain function if they were able to get into the brain in any concentration. Because of this barrier, most of our standard chemotherapy and anticancer drugs simply cannot cross the barrier to reach the cancer cells within the brain. In part, because of this, patients whose cancer had spread to the brain have typically been excluded from most of the clinical trials evaluating new drugs and treatments for breast cancer. The study reported by Lin at ASCO tested the ability of a new HER2-targeted drug, tucatinib, which because of its chemical structure has good penetration across this blood-brain barrier. Earlier smaller studies had suggested that this drug did indeed get into the brain at concentrations that could effectively treat breast cancer involving the brain. In this study, almost 300 patients with metastatic breast cancer involving the brain were treated with a standard chemotherapy regimen with or without the tucatinib. Serial brain scans were obtained in order to measure the response of the brain metastases to the treatment. These were typically MRI scans of the brain.

The study results showed that the use of tucatinib in patients with breast cancer involving the brain reduce the risk of the growth of their brain disease by about two-thirds and improve their overall survival by at least 6 months. These results have recently been published in a more complete form in the Journal of Clinical Oncology. And these results really strongly support the use of tucatinib in combination with the standard chemotherapy regimen of trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer involving the brain.

Although neither of the new approaches I've just described cure the majority of patients treated with either the primary CNS lymphoma or brain metastases from breast cancer, both describe new approaches that really potentially move us further along the road to having more effective treatments for patients with brain tumors. These studies are also outstanding examples of why well-done clinical trials that carefully test and evaluate the beneficial effects as well as the toxicities of new cancer treatments are critical to our goal of finding new therapies to treat our patients with cancer. Thanks very much.

ASCO: Thank you, Dr. Lesser.

Next, Dr. Michael Williams will discuss several studies that looked at new ways to treat different types of lymphoma. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center. He is also the Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. He is also the Cancer.Net Associate Editor for Lymphoma.

View Dr. William's disclosures at Cancer.Net.

Dr. Williams: Hello. This is Dr. Michael Williams. I'm a professor of medicine at the University of Virginia hospital in Charlottesville, Virginia, where I'm chief of the hematology oncology division and the physician lead for cancer services here at UVA. I have a few disclosures, clinical trial grant support from Janssen and Pharmacyclics to the University of Virginia. I've received honoraria for medical education conferences from Xian Janssen, and I have been a consultant for Kite Pharmaceuticals in the past. So what we're going to talk about today are some of the highlights in lymphoma that were presented at the recent virtual meeting of the American Society of Clinical Oncology focused on lymphoma. So the field continues to move forward very rapidly. It's really a dynamic time for advances in treatment of lymphoma and related disorders. The exciting thing is that patients in the not-too-distant past may have had limited options, especially in the setting of recurrent lymphoma. We now have new approaches that are really quite interesting, quite effective, and I think are going to change the way we practice for these particular diseases.

So the first of these I'm going to talk about is for classical Hodgkin lymphoma, also called Hodgkin's disease. So the good news is here, that the vast majority of people with Hodgkin lymphoma are cured by their frontline therapy but not all do achieve a remission, or if they do, they may relapse a year or 2 or sometimes later after their initial therapy. And these patients, historically, have not had as good of a long-term outcome as those who remained in their initial remission. So investigators from an international team of lymphoma experts conducted the KEYNOTE-204 study that compared an immune checkpoint inhibitor - it's a form of immunotherapy called pembrolizumab - versus a standard agent brentuximab vedotin, which is a drug antibody conjugate that delivers a chemotherapy agent directly to the Hodgkin tumor cells. So these were patients who had either not responded to their initial treatment, in other words were considered to be primary refractory, or had relapsed later. Many of them relapsed within 12 months, which is, again, a worrisome timing for relapse in that those patients may be more chemotherapy resistant to traditional treatments.

So in this study, it was a 1-to-1 comparison of about 300 patients. And the study found that those who received the checkpoint inhibitor pembrolizumab had a better response in terms of their remission rate and a more long-lasting response than those patients treated with brentuximab vedotin. At 12 months, about 54% of patients remained in remission as opposed to about a third of patients on brentuximab. Although, there were some continued relapses over the next year, there were some patients who achieved more durable response. So it was a very encouraging finding. The side effects were as would be expected. There were some autoimmune problems with the immunotherapy checkpoint inhibitor and peripheral neuropathy in those who got brentuximab. So these investigators concluded that for patients with this form of relapsed and chemotherapy-resistant Hodgkin's lymphoma, that pembrolizumab should be considered the preferred treatment option and a new standard of care for these patients.

Now, the second trial that we'll talk about relates to a specific form of non-Hodgkin lymphoma called lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. This is a lymphoma where an abnormal immunoglobulin, a high molecular weight IgM, is produced. That can cause problems of hyper viscosity and headaches, vision changes, shortness of breath, in addition to some lymphoma-related symptoms. And what they did is compared 2 targeted agents for people who needed treatment, whether they were relapsed or had not had prior treatment at all for their Waldenstrom's. And the drugs that they chose were Bruton tyrosine kinase, or BTK, inhibitors. These are a very active class of drugs in B-cell lymphomas including Waldenstrom's. And the first of these that became available several years ago and was FDA approved is ibrutinib, and a second agent more recently approved is zanubrutinib. The latter being a bit more targeted to the molecule that we're trying to inhibit in the tumor cells. And it's similar in many ways to a third drug that's available called acalabrutinib.

But in this study, they're comparing ibrutinib with zanubrutinib. And what they found is that, in about 200 patients, that both drugs were very effective in achieving a response. Slightly higher response rates for zanubrutinib, but really no significant difference in the progression-free and overall survival for these patients. So both drugs were very active and very reasonable for treating patients. There were fewer side effects, however, with zanubrutinib, in particular toxicities such as the development of atrial fibrillation and diarrhea or bruising and bleeding, which happened in a small percentage of patients on ibrutinib. So those side effects seemed to be less with the more targeted drug zanubrutinib. So they appeared to be similar in efficacy but perhaps a better safety and toxicity profile with zanubrutinib. Now, ibrutinib is approved in the United States for relapsed Waldenstrom macroglobulinemia. Zanubrutinib is approved for mantle cell lymphoma, so not for Waldenstrom.

So the final entity that I want to discuss is really using a treatment that many of you no doubt have read about. There's been a lot in the news about the use of CAR T-cell, or chimeric antigen receptor T-cell therapy. So this is a form of cellular therapy. And by that, I mean that in patients who have relapsed aggressive lymphoma, usually diffuse large B-cell, a patient who has relapsed disease has T-cells. Those are part of their immune cellular defenses. And those T-cells are removed and they're genetically reprogrammed and then expanded and reinfused to patients. So they're reprogrammed so that the immune effects are targeted against the patient's lymphoma cells. So this is an approved therapy in aggressive relapsed large B-cell lymphoma. But at this meeting, investigators from a number of centers in the United States reported the interim results of a study using a CAR T-cell called axicabtagene ciloleucel, or Axi-cel, for patients with indolent or low grade lymphoma that, nonetheless, is recurring, needs treatment, and has been resistant to at least 2 or more prior therapies.

So I'm going to focus in this study on the results with follicular lymphoma. They did also study a small number of patients with another type of indolent low-grade lymphoma called marginal zone. But looking at the follicular lymphoma patients, they were heavily pre-treated. Most of the patients had had 3 or more prior therapies. Most of them were refractory or, in other words, resistant to the current and the most recent chemotherapy they had received. And about a quarter of the patients had had a prior stem cell transplantation for relapsed disease but had now relapsed even after that therapy. And what they found in the first 80 follicular lymphoma patients they studied is that 95% of them responded and 81% achieved a complete remission. The duration of response was really quite good. So with a follow-up of a little over a year, about two-thirds of patients were still in remission. Whether these patients may be cured of their follicular lymphoma or may experience a later relapse is going to require more follow up, but very promising early results for this treatment of patients with otherwise resistant follicular lymphoma.

There are significant side effects with this type of therapy, including something called cytokine release syndrome, which is like an intense inflammatory reaction. Fortunately, the severe forms of this occurred in a minority of patients, under 10%. There can also be neurologic events that can range from tremor or confusion, and rarely even patients becoming unresponsive. Fortunately, most everyone recovers from this. And in this trial, the more severe forms of these neurologic events occurred in about 15% of patients. So a very promising early set of data for another group of lymphoma patients, in addition to those with large cell lymphoma. So if you are in a situation of highly resistant and progressing follicular lymphoma, including follicular lymphoma that may have transformed from the lower grade into a higher grade large cell lymphoma, then considering a CAR T-cell therapy or a clinical trial of other novel approaches is certainly worth considering.

And I'll finish by just saying that it's a fast-moving field. There's a lot of benefit if you have a newly diagnosed or a relapsed lymphoma to talk with your oncologist and consider whether a second opinion may be in order and what clinical trials might be relevant for your situation because, nowadays, we often find that taking part in such a trial provides access to some of these very promising new agents and allows us to move the field forward and bring these newer treatments online so that they can benefit as many patients as possible. So a very exciting time in the field of lymphoma, lots of important new data presented at ASCO, and I'll look forward to updating you on future advances in another podcast.

ASCO: Thank you, Dr. Williams. Learn more about the research presented at the ASCO20 Virtual Scientific Program at www.cancer.net/blog, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play to catch up on the other episodes in the Research Round Up series.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.  

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today's podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, germ cell, and kidney cancer.

This podcast will be led by Dr. Sumanta (Monty) Pal, Dr. Neeraj Agarwal, Dr. Timothy Gilligan, and Dr. Tian Zhang.

Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Astellas Pharma, and Bristol-Myers Squibb.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Astellas Pharma, Bristol-Myers Squibb, Nektar Therapeutics, and Merck.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. He has no relevant relationships to disclose.

Dr. Zhang is an assistant professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Bristol-Myers Squibb and Merck.

View full disclosures for Dr. Pal, Dr. Agarwal, Dr. Gilligan, and Dr. Zhang at Cancer.Net.

Dr. Pal: Hi. I'm Dr. Monty Pal from the City of Hope. I'm joined today by Dr. Neeraj Agarwal from the Huntsman Cancer Institute and University of Utah, Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute, and Dr. Tian Zhang from Duke Cancer Institute. Today we're going to discuss 3 ongoing clinical trials in prostate, germ cell, and kidney cancer. As you may know, clinical trials are the main way that doctors are able to find better treatment for diseases like cancer. Patient participation is vital for clinical trials. By participating in a clinical trial, you can directly help researchers develop better treatment, reduce side effects, and even reduce the risk of cancer altogether. The 3 trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers Panel from the trials in progress abstracts that were presented at ASCO's 2020 Genitourinary Cancers Symposium. Because these are ongoing clinical trials, final results from these studies are not available yet. I'd like to note that none of us have any direct involvement with any of these trials. To view our full disclosures, please visit the show notes for the episode on Cancer.Net.

Now, the first trial we're going to discuss is the KEYNOTE-641 trial for prostate cancer.  [Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)] Dr. Agarwal, can you tell us who this study is designed for?

Dr. Agarwal: This trial is designed for patients with advanced prostate cancer, or metastatic prostate cancer, who are experiencing disease progression on standard androgen deprivation therapy, a state known as castrate resistant prostate cancer.

Dr. Pal: And if you see these patients in your clinic right now, what is the current standard of care?

Dr. Agarwal: The most commonly utilized [treatments for] these patients include drugs which block androgen signaling inside the prostate cancer cell. And one of the most commonly utilized drugs is enzalutamide followed by abiraterone.

Dr. Pal: Tell us a little bit about how this particular study aims to improve or change the current standard of care.

Dr. Agarwal: Early clinical data showed that adding the immunotherapy agent pembrolizumab to enzalutamide may improve survival outcomes. The response rates in that smaller study were meaningful and were very promising. Based on those earlier data, this trial has been designed and is asking two main questions. Number one, whether adding the immunotherapy agent pembrolizumab to enzalutamide will improve overall survival. And the second question is, whether adding pembrolizumab to enzalutamide will delay disease progression.

Dr. Pal: Are there any risks that patients should be aware of with this regimen?

Dr. Agarwal: Both agents are very commonly utilized for many years now in oncology clinics. Enzalutamide is an oral pill which blocks androgen signaling and is associated with side effects such as fatigue, muscle loss, bone loss, falls, and many others which are relatively easy to manage over time. Pembrolizumab is an intravenous therapy approved for multiple cancer types, and is associated with immune-related side effects. Many of these can be severe in 4 to 5 percent of patients receiving pembrolizumab. These can include diarrhea, abnormal liver function tests, or liver toxicity, a skin rash, lung toxicity, which can include pneumonitis [or lung inflammation]. But most of these side effects can be managed as long as they are promptly detected. So I think education and close monitoring with oncologists is the key for early prevention and management of the side effects.

Dr. Pal: Those are great tenets, not just for this clinical trial but in using these agents in general. Thanks a lot. And final question for you, Dr. Agarwal. Is this trial still open right now? And if so, when do you think we might see some results from it?

Dr. Agarwal: This trial is open across the United States and different parts of the world. And the primary results, early results, will be available, I'm hoping, in 2023, in the middle of 2023.

Dr. Pal: Well thank you for that excellent overview, Dr. Agarwal. I'm going to turn my attention now to Dr. Gilligan to discuss a topic that we don't often have on this podcast. But this is nonetheless a critical disease space for us to discuss. Dr. Gilligan is going to tell us about the P3BEP clinical trial in testicular cancer. [Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours (P3BEP)] Dr. Gilligan, can you tell us a little bit about who this study is designed for?

Dr. Gilligan: Yes, germ cell tumors are cancers that start in the reproductive cells, most commonly in testicles of adolescent or adult men. But germ cell tumors can also start in children - typically not in the testicles but elsewhere in the body - and they can start in women in the ovaries or elsewhere. In children, we sometimes see [germ cell tumors starting in the brain]. Those are not included in this trial. But basically, everybody else with germ cell tumors are eligible for this - men, women, and children - if they have a poor or intermediate prognosis. And just to clarify one more piece about that, this is for people who have advanced stage disease. Again, men, women, or children with advanced stage metastatic germ cell tumors, as long as it didn't start in the brain. And as long as their prognosis is in the intermediate or poor risk category, not the good risk category.

Dr. Pal: So glad that you pointed that out, Tim. I have to tell you that I gave this incorrect label of a testicular cancer study, but critical for our listenership to know the germ cell tumors can occur both in males and females. Can you tell us a little bit about the current standard of care for the patients that are being [included] in this study?

Dr. Gilligan: Absolutely. Chemotherapy for germ cell tumors has been one of the huge success stories of modern oncology, and the cure rate is extremely high. Overall, [we cure about 96% of men with testis cancer.] However, when you start to look at advanced stage disease in intermediate and poor risk patients, the success rate goes down. It's about a 75% cure rate for patients with intermediate risk tumors and 60% for [those with] poor risk tumors. The standard of care has been the same for a long time. It's 4 cycles of chemotherapy called BEP, and that's what has produced those results. And while those results are good, we would like them to be a lot better.

Dr. Pal: So Dr. Gilligan, you've used this term intermediate and poor risk in the context of patients with germ cell tumor. Can you tell us a little bit about what intermediate and poor risk [means]?

Dr. Gilligan: Yes, it's based mostly on where the cancer has spread to and how high certain blood tests are. There are things called tumor markers which are proteins in the blood that are made by the cancer, and the higher those levels, the worse the prognosis. Similarly, if the cancer has spread to certain organs, such as the liver or the bones or the brain, organs other than the lungs, then patients have a poorer outcome and a poorer prognosis. The last category is men and women who have certain germ cell tumors that grow in the chest called extragonadal tumors. They also have a prognosis that's not as good as other germ cell tumors. So it's a little bit complicated, and for patients, when you see your oncologist, they can clearly tell you which prognostic category you fall into.

Dr. Pal: How does this study aim to improve or change the standard of care?

Dr. Gilligan: So mainly we'd like to get those numbers better. And I think the key idea in this study is that with chemotherapy, which is different than the kinds of drugs we talked about in the prior conversation, the philosophy is to basically give patients as much of a dose as they can safely tolerate. And the idea of this trial is that if we give the chemotherapy more frequently - if we kind of squeeze together the cycles so that rather than every 3 weeks we're repeating it every 2 weeks - can we get a better response in killing the cancer without having too much toxicity?

Dr. Pal: So they use this term in the title "accelerated." Is that what you're referring to there?

Dr. Gilligan: Yes. So if you think of chemotherapy as something that is repeated, we're repeating it sooner. And we used to give the patient 3 weeks to recover. On this trial, they're comparing that standard approach every 3 weeks to giving it every 2 weeks. In other words, we're making it denser. You get the chemotherapy faster. And the question is, will we cure more people that way or not?

Dr. Pal: And Dr. Gilligan, any known risks that patients should be aware of as they [consider] a study like this?

Dr. Gilligan: Well I think the risk with this approach is that we may increase toxicity without improving outcomes. Past attempts to do better than the standard treatment have not been successful. And the current standard treatment has been the standard for a long time as a result. We are hoping the new approach will be better, but we don't know until we try it, and it's possible that it will be more toxic.

Dr. Pal: When do you think we might see some results from this?

Dr. Gilligan: I don't know when we will see results. My guess is that it will be within a few years. Germ cell tumors grow quickly; they're aggressive cancers, so you tend to get your results pretty quickly, but I don't know exactly.

Dr. Pal: Dr. Gilligan, thank you for that excellent overview. Last, but certainly not least, we're going to turn our attention to Dr. Tian Zhang for discussion of a very important study in kidney cancer. [A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)] Tell us a little bit about this study and who it's designed for.

Dr. Zhang: PIVOT-09 is a study of a combination of a [novel] immunotherapy called bempegaldesleukin in combination with nivolumab compared to investigator-selected sunitinib or cabozantinib. So these are standard blood vessel blockers. The study is designed for patients with metastatic clear cell kidney cancer who have had no prior medication treatments and also measurable disease that can be followed on subsequent scans.

Dr. Pal: And when you're seeing these patients in clinic with metastatic kidney cancer, what is the current standard of care? What are you using to treat patients these days?

Dr. Zhang: We've known for a long time that kidney cancer will respond to these immune activating therapies, and [it has been demonstrated that a drug called IL-2, when given in high doses,] improved the overall survival for a subset of patients with metastatic kidney cancer and [produced] really durable complete responses for a small number of patients. However, it was highly, highly toxic, and there were lots of patients who ended up in the hospital. It had significant toxicities and patients were treated in the hospital for about a week at a time. So since about 2018, our standard of care immunotherapy options [have included] agents like ipilimumab and avelumab or the combination of pembrolizumab or avelumab with a blood vessel blocking agent. This is an easier way to give immune activating treatments in a more targeted fashion. [With this study we are testing] whether the IL-2 cytokine can be modified and given more in a more safe and effective manner.

Dr. Pal: This is an interesting drug. If I understand it correctly, we're taking IL-2 from yesteryear, a drug that we used more than a decade ago to treat patients with advanced kidney cancer, and we're retooling it a bit for patients to really enhance the efficacy, maybe really enhance the safety of the compound as well. Can you tell us how this compound's doing that?

Dr. Zhang: Right so bempegaldesleukin is a special formulation of IL-2. It's actually a pegylated form of the IL-2 cytokine, so it includes this polyethylene glycol molecule around the IL-2. And this pegylation allows that cytokine to be released slowly [in the bloodstream] so that in itself may improve the side effect profile. And then it also activates the tumor fighting subset of immune cells, T cells and natural killer cells in the tumor microenvironment, without activating other suppressive T cells. So the thought from preclinical studies is that bempegaldesleukin, because of its pegylated form, will actually decrease the side effects while activating the tumor fighting cells in the tumor microenvironment.

Dr. Pal: And in this trial, how will success be evaluated? How will we know the treatment is working, that it's positive?

Dr. Zhang: So the primary objective for this particular trial is a composite of objective responses as well as overall survival, and then secondary objectives include progression free survival - so lengthening time until disease progression - as well as evaluating the safety of the combination and the quality of life for patients who are treated on this combination.

Dr. Pal: Now I remember IL-2, the drug that you referred to, from more than a decade ago, giving it to patients and certainly it came with a lot of toxicity. What are some of the toxicities of patients receiving bempegaldesleukin should be aware of?

Dr. Zhang: Some of the early phase 1 trials that evaluated bempegaldesleukin found that some of the toxicities included low blood pressure as well as syncope where patients would feel lightheaded [or faint,] headaches, edema, swelling in their legs and fluid buildup, as well as infusion reactions. And I think we should also think about the immunotherapy-related toxicities of nivolumab where we're giving it in combination. So diarrhea, rashes, endocrine dysfunction are pretty common. So those would be some of the expected side effects of the immunotherapy cohort. And then we shouldn't forget about the control cohort treated with standard sunitinib or cabozantinib, and those side effects would include hypertension, hand foot syndrome or other rashes, diarrhea, nausea, hypothyroidism, and loss of protein in the urine.

Dr. Pal: Right. Well a final question for you Dr. Zhang. Is this trial still open to patients, and if it is, when do you think we might see some results from it?

Dr. Zhang: Yes, the trial is still open. It's enrolling up to 600 patients total and it's currently open globally in the U.S., Mexico, South America, Asia, Russia, and Australia. I'm hoping we will see results from this phase 3 trial in the next 2 to 3 years.

Dr. Pal: Well thank you very much, Dr. Zhang, Dr. Gilligan, Dr. Agarwal. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team. Thanks so much for listening.

ASCO: Thank you, Drs. Pal, Agarwal, Gilligan, and Zhang.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

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This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

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The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, "What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?" In this episode, editors discuss new research in the fields of head and neck cancer and melanoma.

First, Dr. Ezra Cohen will discuss new research in squamous cell carcinoma of the head and neck and adenoid cystic carcinoma. Dr. Cohen is Co-Director of the San Diego Center for Precision Immunotherapy, Associate Director of Translational Science and leads the Solid Tumor Therapeutics research program at Moores Cancer Center at UC San Diego Health. He is also the Cancer.Net Associate Editor for Head and Neck Cancers.

View Dr. Cohen's disclosures at Cancer.Net.

Dr. Cohen: Hi. This is Dr. Ezra Cohen from University of California, San Diego, Moores Cancer Center. And today I'll be reviewing head/neck cancer abstracts from the American Society of Clinical Oncology Annual Meeting. I have consulted for Merck in the past.

As all of us know, this meeting was virtual this year, but we had an opportunity to see the broadcasts through the virtual website. And there were a few abstracts that I thought were relevant to not only current standards of care but also to the future of research in head/neck cancer. The first one I'll talk about is a Japanese study that compared post-operative chemo radiotherapy of 3 weekly cisplatin versus weekly cisplatin in high-risk patients with squamous cell carcinoma of the head and neck. This was indeed an adjuvant trial or a post-operative trial, and really addressed an important question in the field that had been controversial and perhaps continues to be going forward.

The investigators compared a dose of 40 milligrams per meter squared given every week versus the standard 100 milligram per meter squared of cisplatin given every three weeks and assess patients for local-regional control and overall survival. Interestingly enough and as opposed to some prior reports, the combination of weekly cisplatin and radiation actually proved to be superior with respect to both local-regional control and survival while providing a regimen that was fairly well-tolerated and in the aggregate actually had a lower toxicity rate than the every 3 week cisplatin, suggesting that at least at 40 mg per meter squared, we may have a regimen that is in the post-operative setting more efficacious, and better tolerated, and that it may be time to revisit standards of care or at least to perhaps accept 2 different standards of care in the post-operative setting; one being high dose every 3 weeks cisplatin and the other being weekly cisplatin.

The other relevant abstract from the oral session was another randomized trial, this time from South Korea. Looking at adenoid cystic carcinoma, here patients were randomized to either receive a vascular endothelial growth factor receptor inhibitor named axitinib vs. placebo in patients with metastatic disease. This class of agents that axitinib belongs to has been noted to be active in adenoid cystic carcinoma for some time, but there had never really been any randomized trials comparing axitinib to any treatment and certainly not to observation or placebo. Fifty-seven (57) patients were enrolled and progression-free survival was the primary endpoint, in fact, 6-month progression-free survival. And what the investigators found was that this was much better in the axitinib patients versus placebo. In fact, about 70% of patients in the axitinib arm failed to progress and were still alive versus only 23% in the placebo arm. Now, this was not a large enough trial to change registration or the label of the drug, but it certainly, for patients with adenoid cystic carcinoma who have very few treatment options, does provide a therapy that now is at the very least validated through a randomized phase II trial and gives us a little bit more confidence in using this entire class of agents in patients with adenoid cystic carcinoma.

One of the other targeted therapy studies that I think is also worth highlighting from the meeting was that using tipifarnib in patients with HRAS mutations. This was a study conducted across several different cancer types, but the most commonly enrolled patients and, in fact, a specific cohort were for patients with head/neck squamous cell carcinoma. And interestingly enough, the investigators having enrolled 18 patients found an overall response rate of 56%, arguably much better than we would be able to do with chemotherapy in these patients or any other targeted agent for that matter. And again, not a study that would change the label or standards of care but certainly worthwhile watching the efficacy of this agent tipifarnib going forward in patients with HRAS mutations.

And then from the poster discussion session, I think we saw some interesting data that may be a prelude to the future, especially with immunotherapy. Christine Chung presented the experience of cetuximab and nivolumab, an EGFR and a PD-1 antibody in combination, and found that to be quite active, again, in a non-randomized manner but certainly enough activity to think about taking that regimen forward. Dr. Roger Cohen presented the monalizumab and cetuximab data in patients with recurrent or metastatic disease in this time in a cohort that were both platinum and PD-1 refractory, so a heavily pre-treated patient population, and very nicely finding a response rate of 20% in patients with squamous cell carcinoma in the head/neck. And then lastly, along the lines of immunotherapy, an update on the data within ICOS agonist GSK3359609 in combination with pembrolizumab in patients who were treatment naïve with head and neck squamous cell carcinoma or at least PD-1 treatment naïve and again finding some promising activity with a response rate of about 24%.

The latter 2 trials, the monalizumab-cetuximab and the ICOS agonist pembrolizumab studies, are in fact now moving on to Phase III studies. And so again, there may be a change in the standard of care using some novel I-O regimens, and it's something to look out for in the future.

Thank you for listening to this review of head and neck cancer abstracts at the American Society of Clinical Oncology Annual Meeting and have a nice day.

ASCO: Thank you, Dr. Cohen.

Next, Dr. Ryan Sullivan will discuss several studies across the field of melanoma treatment. Dr. Sullivan is a medical oncologist and Attending Physician in the Division of Hematology/Oncology at Massachusetts General Hospital. He is also the Cancer.Net Associate Editor for Melanoma and Skin Cancer.

View Dr. Sullivan's disclosures at Cancer.Net.

Dr. Sullivan: My name is Dr. Ryan Sullivan. I am the associate director of the melanoma program at Massachusetts General Hospital in Boston, and I'm here today to give a summary of some exciting data that was presented at the 2020 Annual ASCO Meeting which, of course, was presented virtually. I have a few disclosures, including that I have served on advisory boards for a number of companies whose data was presented, including Bristol Myers Squibb, Merck, Novartis, and Iovance. I'd like to start, really, by thinking about how a patient's journey with melanoma begins and then moves on through various stages of treatment, because there were a number of very interesting abstracts and presentations presented this year that include important breakthroughs in many different steps in the patient's journey. The first, of course, is a diagnosis, and soon after a diagnosis, often, the next step is surgery.