ASCO Education

Can you hear me now? In this episode of the ASCO Education Podcast, host Rami Manochakian (Medical Oncologist, Mayo Clinic Florida) discusses Telemedicine with medical oncologists Ana Maria Lopez (Sidney Kimmel Cancer Center), Estelamari Rodriguez (University of Miami) and Douglas Flora (Executive Medical Director or Oncology at Saint Elizabeth Healthcare). Subscribe: Apple Podcasts, Google Podcasts | Additional resources: elearning.asco.org | Contact Us Air Date: 5/20/2021   TRANSCRIPT [MUSIC PLAYING] ANNOUNCER: The purpose of this podcast is to educate and inform. This is not a substitute for 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. [MUSIC PLAYING] RAMI MANOCHAKIAN: Hello, and welcome to the ASCO Education Podcast. Today, we will be discussing the challenges and benefits of telemedicine in oncology, something that has become especially important over the last year in the wake of COVID-19 pandemic. My name is Dr. Rami Manochakian. I'm a thoracic medical oncologist and a vice chair for education at the heme/onc division at the Mayo Clinic, Florida. As the host of today's podcast, I am very excited to be joined by our three distinguished guest speakers. And I'll let them introduce themselves. ANA MARIA LOPEZ: Hi, my name is Dr. Ana Maria Lopez, and I'm a medical oncologist and an integrative oncologist. And I am professor and vice chair of medical oncology and chief of the New Jersey Division of Cancer Services at the Sydney Kimmel Cancer Center in Philadelphia, Pennsylvania. RAMI MANOCHAKIAN: Welcome. ESTELAMARI RODRIGUEZ: Hi, I'm Dr. Estelamari Rodriguez. I am an associate director of community outreach and co-lead of the Thoracic Sciences Group at the Sylvester Comprehensive Cancer Center at the University of Miami. DOUG FLORA: Hi. I'm Doug Flora. I'm a treating medical oncologist. I'm also the executive medical director for oncology here at Saint Elizabeth Health Care just out of Cincinnati, Ohio. RAMI MANOCHAKIAN: Great to have you all here. Without further ado, we'll go ahead and start with our first questions. We all agree, this has been a very, very hot topic lately. And it's probably, for quite some time, it's going to continue to be. When we talk about telemedicine, specifically in oncology, what are some of the main advantages of telemedicine and oncology for patients and for providers, respectively? DOUG FLORA: So obviously, this year, we dealt with a lot being handed at us. And I'm glad that we're coming from three different sections of the country because I think our perspectives will be unique. I'm coming from a community aspect here. We have about four or five hospitals in our system. And I practice in a place that's partially Cincinnati-based, and partially some patients from deep and rural Appalachia. And so obviously, there's some access issues that I think we'll talk about a little bit later. I will say, in our system, it was interesting. We've been trying desperately to get our doctors to embrace telehealth before coronavirus landed on our shores. And it was a struggle as you guys know, and I think we'll talk about. There were some reimbursement issues, and the way that we approached this as a system was not finding traction with the providers. So we went from about 250 patients on virtual visits or telehealth visits the year prior to COVID, to almost 250,000 in our large physician group the year after. And so I wondered if you guys had a similar experience where you were sort of pushed off that burning platform and all of a sudden, had to adapt to technologies that were maybe used in regular world but not yet in medical world yet. So how are things in Miami, Dr. Rodriguez? ESTELAMARI RODRIGUEZ: So at the beginning of the pandemic, as a system, we turned all our visits from in-person to, overnight, telemedicine. And we had a system where you could connect in our electronic medical record via Zoom. But our patients didn't have that system. So there was a large kind of growing pain in terms of getting the patients adapted to the technology. And still, a year later, patients have a tough time with the technology. But I think one of the great advantages of telemedicine, and we have learned, is that it really brings the medical visit to the patient in a different way that we were not doing before, so that I can share with you, we had patients during the pandemic where our doors where close to families and we were able to continue communications with patients and their families. I had one visit where the children joined conversations from, like, Los Angeles, New York, and Miami. We were all in the same virtual world really talking to the patient about a new diagnosis of lung cancer. And that was, I think, where it was a different-- it was a discussion that we couldn't have had for many reasons, because it would have required travel. It would have required a lot of expense from the children having to take time off work. And I think our patients, especially in the community, really embraced the idea of being able to be at the doctor's office without having to take time off. We know that it's a lot of financial toxicity to our treatments and driving into the city to get into the cancer center. So that's one thing that I think telemedicine will be here and continue because patients wanted that. They wanted that access to the patients when they needed. And they wanted to have more family members in the visit. And then, one thing that we also have done, we have some diagnosis that we have to coordinate care with different specialists. So we started a multidisciplinary clinic in thoracic oncology during this time. And in one disease that it has really helped us has been in mesothelioma. So these are very rare cases that require complex surgeries from rehab doctors, pain management, thoracic surgeons. Sometimes, we need surgical oncologists for the abdomen. So that's a lot of medical visits. And we've been able to have all of those visits at once for the patient. So I think, really, it's allowed us to provide care for patients in an expedited way, in a more kind of effective cost-saving way for the patients. And also, to have these conversations between specialists in the same virtual space with the patient makes the patient feel like they're at the center of this discussion. And it's more transparent. So I think that we have learned that telemedicine can be used for really, making care more comprehensive. And I think we have more challenges. And Dr. Lopez, I wanted to hear about your practice, how you have integrated telemedicine and the challenges of trauma medicine. ANA MARIA LOPEZ: Thanks. Thanks. The multi-D clinics sounds fabulous that you've been doing. You know, one of the things, of course, for all of us, has been that telemedicine has allowed people to stay safe, clinicians to be safe, patients to be safe, families to be safe. And I think of myself as an old-time doc because one of the things that I really love about it is because it's brought back the house call. So we get to be at the bedside with our patients, be where they are. Some people call it getting back to the website, which I think is a great term. But really, we're where the patients are. We learn so much more by seeing them in their home environment. And also, seeing who's living with them, who's close with them in a much more intimate way. So I think those are factors that are really tremendous advantages from the perspective of helping to take care of people. RAMI MANOCHAKIAN: Yeah, I love all these ideas and thoughts. I mean, we clearly all have felt it was maybe hard at the beginning. And I know we'll talk about this throughout, but then, it came with a lot of advantages. And I would add, probably, a couple of things as well. I think patients, when they are being considered for clinical trials or being referred to another center, or for a second opinion, of course, we know we're missing the medical exam part. We're missing certain things. But sometimes, we ended up saving many patients that trip, and get them into the multi-D clinic after knowing exactly what we want. Certain things that we used to do by reviewing the chart and maybe on the phone, and now we have an official introductory visit save them. The other thing where it helped me a lot, and I'm a thoracic oncologist, is after the first visit when I sent a bunch of testing, genomic testing scans and others, and I want to schedule a follow-up to go over the results and set a treatment plan and the patient lives a few hours away, and we want to make the next visit maybe the treatment visit. So this is where, actually, it helped a lot. So we set this video visit, reviewed all the results, set a treatment plan, discussed. And every patient essentially loved it. So I'm glad we all share the same feelings. Speaking of which, of course, any new things come up. I don't know if we could call it new things, but when telemedicine kicked in, as Dr. Flora mentioned, at the beginning, everyone was nervous. And once it started rolling, even though it rolled very smoothly nationwide, but it still came up and will continue to come with some challenges, some drawbacks, maybe some limitation, whether it is a technology, infrastructure, communication. So I would love to hear your thoughts about what kind of challenges you've experienced or you continue to experience, or maybe you think may happen down the road with telemedicine and oncology. ESTELAMARI RODRIGUEZ: So I will share with you, in our community, we have a very large Hispanic population of different educational backgrounds. So I think one thing that became very clear to us is that we do have a digital divide in this country. And all our patients can't adapt to this technology. And a lot of the technology was not developed for telemedicine, was not developed for older patients that have difficulty in hearing, that may need interpreters. So there's a lot of things that were not thought out because we didn't know we would be in this position. But I hope that the technology will evolve to be more user-friendly. We try to kind of make it work. So we had a system that is HIPAA compliant, we assume. But there were patients that we would have to connect with them by WhatsApp out of emergency, which is something that a lot of our older patients are used to using with their families in South America and to stay in contact with family members. So we tried to adopt what they knew, what they were comfortable with, with what we had. But ultimately, we hope that we come out of this with a better system that can reach different patients that have different needs. So, Dr. Lopez, I wanted to hear from you, from your experience in your community, how you've been able to reach this digital divide. ANA MARIA LOPEZ: Yeah, I think that's such a great point. And certainly, the whole COVID/telemedicine experience has exposed so many gaps in where telemedicine, which is intended to increase access, really, there are clear barriers. And that's one of them. So there are folks, as you were saying, with WhatsApp or even just with audio, that we've been able to manage, and whether it's elders. And we really need more research in those areas to see what are the areas where this could be effective, and what does sustainability look like when there's this variability in digital knowledge and digital access? Are there ways to get technology to people? So we were fortunate in that we were able to get technology to patients. But having technology and being able to use the technology is not the exact same thing. So really, having to ask, as part of our clinical history, do you have stable internet? If you have stable internet, do you have a device? If you have a device, can you access the portal? And if you can access the portal, can you access a telemedicine visit? And only after all of those questions, to then be able to say, OK, let's do a test visit and see how that works. So we really had to change our thinking a little bit. And then, some of the comments that have been made around the physical exam and. Dr. Flora, I'm sure that that's something that you've experienced. And maybe, what's your sense of the limitations of assessing people at a distance? DOUG FLORA: I love the webside visit. And it really is a house call for us. I would say that initially, the barriers were steep. We would log on, and you're used to an every 20 or 30 minute schedule in my office. And you'd spend 15 minutes trying to figure out how to turn their mics on. And as you guys have suggested, this digital divide is still pretty deep where we live and practice. The majority of our cancer patients are over 60 or over 65. A lot of the ones that we're taking care of live in rural areas that may not have access to broadband or good cellphone access, or at least shoddy cell phone access on occasion. And computers are largely non-existent in a lot of my older patient population. So we've had to meet them where they live. I would say also, we're dealing with a lot of social determinants of health and health literacy. And while there might be an advantage reaching some of these rural populations, on the other receiving end, they've got to have the technology and the ability to log on to talk to us. So like Dr. Rodriguez, we did pivot a little bit from our beautiful HIPAA compliant, EPPA built-in software to FaceTime or just telephone calls. And it was what we had at the time. And I think everyone adapted as we needed to. But as we move forward to sustain this, I think you're correct exactly, that we need to look at the research to understand that when we adopt this permanently, which seems like it's going to be the case, that it's with methods that improve patient care outcomes, and that we're careful to abandon elements that harm patients or widen these disparities that we've just identified. RAMI MANOCHAKIAN: Great points, I think, by all of you. The one thing I would add also and I know was brought up, is there are certain times or certain scenarios where maybe from a communication standpoint, that I felt maybe a video visit, telehealth visit wasn't ideal, especially with breaking bad news or sharing scans. Fortunately, most of the time, when there is a scan, right, we order a lot of scans to assess response. And the patients are here anyway. So these happened to have it be as an in-person visit. I've had patients where their scan was a few days before, so ended up the result was a telehealth visit. And I felt that probably, even though there was an eye contact, I could argue. I had a fellow with me who said, well, the patient was surrounded by multiple family members at home. So even though we breaked not a good news, per se, they were able to take it. But I still felt it was a little awkward moment. And I would say, usually, like a major visit, scan assessment, change in treatment plan, I would prefer for them to be in-person. But to your point, maybe we need some research, more understanding, as it could go either way depending on what patients favor. But great. I think we can move on to another question. ESTELAMARI RODRIGUEZ: I was actually going to add something. So one thing that I have realized and I have kind of told my patients is that this is still a visit to the doctor's office. So I have seen that over time, people have very busy lives and they think they can do the telemedicine consultations while they're driving or they're watching TV. So there's a lot of distractions. And to your point, some of these discussions that we have with patients require preparation. You don't know who's in the room with the patient. Maybe these are news that they don't want to share with the whole group. So I try to make it very serious to our patients and our nurses ahead of time, get information from them to tell them, your doctor will be coming to the room, the virtual room. And this is a visit. You can't be in the car. I mean, these are really serious conversations. So I think we have all seen that telemedicine can be used in different settings when people are busy. RAMI MANOCHAKIAN: Yeah, Great point, absolutely. Absolutely. And one quick thing I would add also, I think it was brought up that video and audio, to me, when it's an only audio, that's almost like a phone call that we all do all the time, supporting our patient and calling them. So we've had patients that the video didn't work out so we switched it to audio. But for me, I'm always trying to avoid just an audio visit on the phone. I know now the new system would let you make it as an actual visit and bill for it. But I think to me, the real telehealth is an audio/video, actually seeing the patient face, some eye contact. I would consider a lack of video in some instances is a major barrier. But hopefully, we're kind of overcoming that. ANA MARIA LOPEZ: But again, really, such an opportunity for research. You know, let's answer the question prospectively. And at least, to me, something that was always so shocking was that telepsychiatry is so well-documented. And some of that is in audio only. So I think the questions are wonderful because it's really allowed us to raise the questions. And now we can really think, how do we answer these questions? RAMI MANOCHAKIAN: I think this would be a very good segue to our third question. From your experience, what are some of the best practices for conducting, I guess, a well-designed or productive telemedicine visit with the patients? What are the keys for a good successful visit in your opinion? And I'll start with you, Dr. Flora. DOUG FLORA: This is another adjustment for us, wasn't it, guys? I can't tell you the number of patients who don't know where the lens is on their computer or on their camera. And people are looking all over the place. And I found that maybe taking a moment to reintroduce the concept of the visit. Can you see and hear me OK? Because not all the time is the audio getting across as clearly as I think it is. I tried to make sure that I was really looking into the camera so that there was that sense of intimacy that you'd mentioned that a doctor and a patient share when they're at the bedside together. So actually, I start my virtual visits. I did one yesterday and we start by a tech question. Are you able to see me? Are you able to hear me? Thanks for allowing me into your home. And then, I do take a moment to sort of reflect on the place that the patient is living. And this is a unique opportunity to go into their cave and see how they live. Are they disheveled? Is it messy? Are they hoarders? Is it a safe place? Does it look like somebody who's keeping up with their life? And I did think also, part of the visit that was unique for this is we see them without makeup on. We see them without earrings and lipstick and the things that you put on before you go out in public. So a lot of times, I would find them in their night clothes or their pajamas. And so the visit would proceed. We're doing a physical examination while they're talking. And you could see them showing you around their living room. And you can see their eyes moving in four directions. And I think for us, the adaptation is, is you actually can do a pretty decent physical examination if you're careful to ask the patient to participate. And we got pretty adept at it. And so now, I think most of us probably have figured out how to do things like patient's not having any retractions. There's not any obvious accessory muscle use. The breathing is non-labored. There's no grunting. It's a pretty good assessment that the lung cancer patient is OK, not as good as we'd like to see if we can use our stethoscope on the back. But it's also not as bad as it sounds when you looked at it at first glance. So what other adaptations did you guys make? ESTELAMARI RODRIGUEZ: I think Dr. Lopez mentioned something that we have done as a system, where we have, at the moment of making that appointment, we're trying to identify which are the patients that will have issues with the technology. So we make that as part of our screen. So we spend more time prepping that phone call. And I also take the point that one thing that has helped and made the patient part of the team, we have asked patients to take their own weight. And some of my patients with lung cancer, they have purchased a pulse oximeter. So they are able to give us part of their vitals. And we have learned, and they have learned, that that makes the visit more useful and get more information from them. So the patients can participate in a way that they were not before. But I think it's important to really understand what the barriers will be upfront. Because you really have a 15-minute visit, and it's not the time to learn how to get an interpreter or learn how to set up the computer. I mean, it's a lot if you want to keep the day going. RAMI MANOCHAKIAN: Yeah, I like those thoughts. It's prepping. Obviously, we're sharing all that we need to prep well and set good expectations. I have a lot of good questions that I think our audience would be interested. So I'm going to, for the interest of time, I'm going to keep moving. A probably related question, and I'll start with Dr. Lopez, considering all that we've discussed, can you tell us how telemedicine-- we've been doing it for a year at least now-- have impacted your existing relationship with patients and family, and affected building maybe future relationships with that? ANA MARIA LOPEZ: Thanks. I do think that one can create good relationships, even if it's online. And I know that was something we all had a lot of hesitancy about, especially at the outset. And certainly, some of the initial thinking around telemedicine was that this would only be for follow-up visits. And again, sort of being an old-time doc, I think I had some trepidations around that. But I really think you can. And part of it, I think, is training for us. So we've talked about the education for the patient and setting the stage what to expect, but also for us. How do you look at the camera so that the patient feels that you are engaging? Pausing, speaking more slowly, intentionally giving patients space to communicate. I think all of these are factors that we can do, and probably would help us in our in-person communication as well, but that really helps us to stay connected. I think the point that Dr. Rodriguez made of, you want to know who all is in that virtual room. So who's at home with you? Let's bring them into the conversation if the patient would like. Or, if the patient really seeks privacy, is there a way that we could have this encounter be more private? So I think all of these things that we normally kind of do to help patients be at ease, we just need to translate to the tele space. But I think that there's a lot that can be done. I think there's a lot that can be done from an educational perspective. And then, when we finally meet in person, even though we're masked and all of that, I think people can really feel connected to us. I wanted to share just very early in doing telemedicine. And this was-- I was accompanying an infectious disease colleague. And he was talking with a patient. And at the end, it was the patient's first telemedicine visit. And so at the end, you know, well, how was this for you? How different? What did you think? And at the end, all the patient said was this was great. The only thing I miss, and the patient went up and hugged the monitor. And I do think it is something that we miss. But there's a lot that we can do. RAMI MANOCHAKIAN: Absolutely. Absolutely. Great thought. And Dr. Flora, I loved when you mentioned earlier, you thanked the patient for welcoming us in their home. I think that was a great way to start things. What kind of feedback you heard, Dr. Flora, from patients? You've been doing telemedicine for a while, and as far as the relationship and their thoughts on this? DOUG FLORA: I'll tell you, I was surprised it's a delighter. We think they want to be with us because we're doctors. And who wouldn't want to come see these minds? And that's not the reality at all. And you know, I would say almost exclusively, the patients have benefited from it and have told me so. They prefer getting that hour back. Ours is a place there is a good travel burden for the majority of patients that we treat. And you know, obviously, it's very challenging. I'll say as a hematologist, sometimes, I'll check a patient's platelet count. And it literally is a 5-minute lab draw. And we can tell with really good certainty that that patient is in good shape and didn't need to make a 45-minute drive and a 30-minute wait and a 45-minute drive. So I would say they've been appreciative that we're now able to care for them in a compassionate fashion that's thorough and that answers the questions that they have. And if we're fortunate enough that that patient's care didn't require a breast examination that day or tapping out a pleural effusion, then I think everybody wins. And I'm not discounting the utility of a physical examination, but in oncology, the honest answer is, is sometimes, it is discussing a formal whole body PET/CT. And I'm going to get an awful lot from that right before I make my call. And it's probably not as important that day specifically that I put my stethoscope on the patient as it was maybe three weeks prior before the scan. RAMI MANOCHAKIAN: True. True. Great points, great point. And on a kind of related note, my next question I'll ask Dr. Rodriguez. At your institution, how have you or other providers adjusted to telemedicine during the pandemic? We've be doing it for a year. We learned through it. What approaches or maybe protocols or certain training or things that you've asked for from IT, or your own division or support staff, so you can accommodate patients in telehealth visits? ESTELAMARI RODRIGUEZ: So I think that we had a video, like a tutorial. But really, you learn by doing this over time, what works for your practice. One of the things that besides doing the prep work of really getting the technology in line and moving the visit alone and having our nurses speak to the patients before you go online, we have also learned that patients can take their own vitals. So I think that's one thing that we have incorporated. We have learned that we can talk about clinical trials and have some of those conversations that would have required a different visit at that point. And I think overall, the providers have appreciated that they can, once they get the system running, we can see more patients. And we can access them when we need to. And like you mentioned, some of these conversations are quick conversations, but they need to be had. And sometimes, you see a patient that had chemotherapy, and you would have liked to see the patient the week after just to check on, and really, to have them drive for an hour and wait for just a quick checkup, where you could do online. And that really has changed my practice and has allowed me to keep in contact with the patient more often, especially basic practices that don't have enough clinic space. Like some of our practices don't have enough parking. They don't have enough clinic space. So we really have adapted well to the telemedicine option to provide care for patients. But again, we still have to incorporate other things that we don't have, like the interpreters, the hearing, patients that cannot hear well. So there's things that we need to work on to make it more user-friendly. RAMI MANOCHAKIAN: Absolutely. Dr. Lopez, anything else you've done differently, or your team has done differently to adjust? ANA MARIA LOPEZ: So we had sort of a series of modules. But I completely agree that you sort of learn by doing. And I think that there are opportunities to bring in. So we're experimenting with this virtual waiting room, so that the MA comes in, sees the patient. The nurse then does what they normally have done, and then the clinician. And then similarly, at checkout, so that it's like including all of the pieces that would have taken place during an in-person visit and involving the whole team that normally engages with the patient. So I think, again, this is definitely evolving. And we're, I think, making it more like the regular in-person visit. RAMI MANOCHAKIAN: One thing I would add also, as a fellowship program director, we were at the beginning wondering, how do we include the trainees, the fellows, the residents? There are some providers who would say, I would just have the fellows or the trainees see them in-person and not do the video. But the longer we've gone through this, we realize this is actually an important training experience, and not necessarily, but here we go where we are we and the trainees have zero experience in this. So we kind of learned from each other and support each other. But there are also, I think having the trainee, the fellows in the room. Sometimes, we had logged in from two different computers. I think it helped and it also showed the patient that the team hasn't changed. We've had pharmacists sometimes join if there was some education needed. But I, again, needed some adjustment, needed some IT help and so forth. And we continued to learn through the process. Dr. Flora, I think there is a very important question that has been always posing itself during this year is, when it comes to billing and documentation, how has the use of telemedicine affected that? Many of you know actually maybe participated ASCO advocacy at the Congress, one of the major bills that we've been advocating for is future keeping of telemedicine. Because ultimately, as far as being able to build and generate the proper income since we continue to invest. And we're doing the same care we do for our patients but in a telemedicine mode. So how was it different for you, Dr. Flora? Any challenges there? DOUG FLORA: Well, you know, I participated in some of that lobbying. And I do it at the state level. And we just did it at the federal level as well. And I think it's great that the oncology community is coming together as our patient advocacy groups. Our first question, we established that it's time-saving. There's cost-saving advantages both for patients and payers. Helps with child care, helps with people being away from work. So it's actually a good thing for society in addition to the good thing to keep us afloat during COVID when they can't come to our office. The CARES Act was voted on and enacted March 6. And since then, we've kind of had the trust of the federal government to say, do what you can to take good care of patients. And for that to be sustainable, I think we've discussed that it has to be in an evidence-based fashion to say that we're not just accepting these things because it's easier care, but that we're actually making sure that we provide the same level of care that existed prior to the pandemic. And so some of the sustainability stuff that is in the proposed laws, we'll touch on that, making sure that we're still documenting well, making sure that as we build, we really are providing the service that we said that we were, which I think the majority of physicians take very seriously, to say that we did the work that we've claimed. And so we've all adapted with virtual physical examination. We've adapted with having the patient take their own heart rate or weigh themselves, as we've discussed earlier. I love the idea of a home oximeter. My wife bought one at the beginning of COVID, but most of my patients probably didn't. So as we move forward, we're seeing this move into research infrastructure for checkups on patients who are on trials at remote sites. And I think that the train has left the station, according to everything that we've seen from Medicare and our consultants who we've engaged in. Now we have to figure out how to make it work and make it sustainable. But it's not going to go away. RAMI MANOCHAKIAN: Absolutely. Dr. Lopez, any comments on the billing or the documentation portion? ANA MARIA LOPEZ: You know, I actually really love to do telemedicine from the documenting perspective. I have a lot of difficulty using the computer during the patient visit. I just don't feel right. So like right now, I could be typing and you might not see me typing. [LAUGHS] RAMI MANOCHAKIAN: We all do that sometimes. ANA MARIA LOPEZ: So, anyway, I do think, as Dr. Flora was mentioning, there are lessons to be learned. And we like working with our legislative colleagues to be able to have the sustainability. But yes, very important to keep the documentation in sync with the billing aspects. RAMI MANOCHAKIAN: Absolutely. Absolutely. And we're kind of coming close to our last question, which again, a good segue from what you just mentioned, lessons learned. You know, I think we all believe clearly that telemedicine in general and in oncology specifically is here to stay. What lessons, what kind of last notes if you want to mention? And I'd like to hear every one of you saying what lessons you've learned, what lessons you want to take moving forward so we can keep telemedicine and oncology, and continue and strive to provide our oncology patient with the best possible care? And I'll start with Dr. Rodriguez. ESTELAMARI RODRIGUEZ: So I think it's upon us to make sure that telemedicine breaks barriers, doesn't create more barriers to our current care. So I do worry about our older patients who already feel like they have been left behind by the whole technology divide. So I think we really have to work hard in understanding what's the best way to communicate with patients that have difficulty hearing, may not understand the technology. We have to develop better systems for them. But overall, I think it's a great addition. It does break barriers for patients that you cannot reach physically, or they may spend a lot of money coming in and driving and taking time from work. But again, we have to keep in mind that we don't want to leave parts of the population behind who are not easy to get into technology. RAMI MANOCHAKIAN: Great. Dr. Flora? DOUG FLORA: Well, as I mentioned when I said the train has left the station, the future is now. And so we can either have this thrown at us, or we can do it ourselves. And I would say that in our center, we're really looking to expand upon this. And we're looking more into more home care, and how can we deliver chemotherapy safely in the home? I think we would all be remiss if we didn't start to really look at the landscape of these devices that are available at home. You know, anybody who's ever worn an iWatch now knows that you can send them your own EKG to your own phone in a matter of two or three minutes. Why can't we get a pulse of a patient with an appropriate device? And these things are here and the economies of scale are driving these down. So eventually, in the next three to five years, I think a lot of these technologies will be democratized and in every patient's home, even the 65-year-olds, because it's a watch that their daughter buys them. And I think when we start to plan for things like that, we're going to find ourselves meeting the patients where they are, which is where they want to be in their living room, effectively and safely. RAMI MANOCHAKIAN: Couldn't agree more. Dr. Lopez? ANA MARIA LOPEZ: I feel like telemedicine is a new translational science. We're beaming people in wherever we can and seeing how it works and seeing the outcomes. And we've talked a lot about bridging the distance between patients and physicians, patients and clinical care teams. But there's also the opportunity to bridge the distance between clinical teams. So that's another potential benefit. And I think it's really made us better clinicians, because we're doing these exams now that are primarily observational. So I feel a little bit like Sherlock Holmes. Your observational skills, I think, are really sharpened with this opportunity. So I think there's a lot of benefit. There's a lot that we've learned, and there's a lot that we still have to learn. RAMI MANOCHAKIAN: Absolutely. Absolutely. Unfortunately, that's all the time that we have for today. Otherwise, really, the conversations have been so good that I could have taken this for hours to come. I'd like to thank every one of you for your participation in this episode of ASCO Education podcast. It was, I think, a very productive and insightful conversation. I think we all agreed that we're helping patients with telemedicine. And I think many of you, or all of you said it best, is that we learn from the lessons. We've built up on the strength that we've already come across, and then looked for rooms for improvement. And it's an area of research, as Dr. Lopez mentioned. And keep looking for how could we enhance this further, because I think we're going to keep doing it for a very long time. Thank you again, very much. I appreciate your time. [MUSIC PLAYING] ANNOUNCER: Thank you for listening to this week's episode of the ASCO E-Learning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

Recent approvals of PARP inhibitors mark the beginning of precision medicine for prostate cancer. Through patient case scenarios, Drs. Lisa Holle (Oncology Pharmacist, University of Connecticut) and Pedro C. Barata (Medical Oncologist, Tulane University) dive in-depth into appropriate use of olaparib and rucaparib in clinical practice, including patient and disease factors to consider. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: elearning.asco.org | Contact Us   TRANSCRIPT [MUSIC PLAYING]   ANNOUNCER: The purpose of this podcast is to educate and inform. This is not a substitute for 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. [MUSIC PLAYING] LISA HOLLE: Welcome to the e-learning ASCO podcast on PARP inhibitors in prostate cancer. I'm Lisa Holle. I'm an associate clinical professor at the UConn School of Pharmacy, and I practice at UConn Health's Carroll and Ray Neag Comprehensive Cancer Center in Farmington, Connecticut. I'm joined today by Dr. Pedro Barata from Tulane University, New Orleans. PEDRO BARATA: It's great to be here with you. LISA HOLLE: Same here. PEDRO BARATA: So, Lisa, I know we'll be talking today about PARP inhibitors in prostate cancer. And it's kind of a kickoff, you know. What do approvals of the different PARP inhibitors for patients with advanced prostate cancer mean to you? LISA HOLLE: Yeah, this is a really exciting time in prostate cancer, because this is really the introduction of precision medicine in the treatment of metastatic castrate-resistant prostate cancer. So this is a group of patients, traditionally, who can benefit from PARP inhibitors that have not had good responses in the past to our traditional treatments. In fact, it really does allow these patients who would be eligible to receive PARP inhibitors to have an extended time on active therapy. Now, as we know with metastatic castrate-resistant prostate cancer, we can't cure the patients, but we can extend that time that they're on active treatment. In fact, in the two studies that were conducted, the PROfound study evaluating olaparib, and the TRITON2 study evaluating rucaparib, the progression-free survival time on average was about eight months. And in the PROfound study, which compared it to our new generation hormone therapies, that really doubled the progression-free survival time. And recent overall survival time was also improved by about five months. So this is really a significant advancement for these patients. And it really underscores the need that we have now for our metastatic patients to do germline and somatic mutation testing to see if they might be eligible for these treatments in the future. So Dr. Barata, who do you think could best benefit from the PARP inhibitors in prostate cancer? PEDRO BARATA: Yeah, and also, it's a great question, by the way, great introduction to the topic. And you indeed touched on something very, very important. And I think it's a perfect segue way for your question, which has to do with can you identify the good actors or the patients who are likely to respond, right? So when you think about how these drugs were developed, if we started by classifying this group of genes known as DNA repair genes, right, who have this job or function of repairing defects at time of cell replication. And so among these different genes, we start talking about BRCA, BRCA1, BRCA2, ATM, CDK, you know, RAD51, FANCA, et cetera. And so it seems like patients who harbor a defect in one of these genes are actually more likely to respond to these therapies. And these therapies, by the way, they inhibit the PARP and the enzyme that helps with burying the DNA, if you will. And so, you harboring a defect in one of these enzymes actually helps you to kind of amplify the benefit of this therapy. So what I'm really describing is a test who can find those defects, those gene differences. And we can do it in both ways. We can test the genes patients were born with. We call that germline testing. And we can also test a tumor for dose alterations. And that's also known as somatic testing, right? And we now know that germline doesn't tell you all the story and somatic doesn't tell you the full story. And so getting both tests seems to be helpful because it's a way of not missing the biomarker positive patients, or in other words, patients with DNA repairs, who are, again, likely to respond to these therapies. And so I would say, among these, definitely, patients with DNA repair defects. And we start learning a little bit more that not all the genes defects are the same, I mean the same in terms of efficacy signal. I guess we can talk about that a little bit later today. But I have to say, we expect somewhere 20% to 30% of patients who harbor dose genomic alterations. And so we are talking about a subset of patients within the group of advanced prostate cancer who really harbor those gene defects, and based on the data we have today, are destined to do better on these agents. Now if we don't test, we don't find, right? And so that's something that I think the clinics overall across the country and really, around the world, are now adapting to develop an easy way to start offering germline and somatic testing to those patients. Because it does impact our decisions. And so I kind of-- I just alluded briefly. And you did say, Lisa, you did talk about PROfound and TRITON that developed, respectively, olaparib and rucaparib, right? Do you have any thoughts about factors that makes you choose one versus the other? Is that something that you kind of use in clinic and to go through that thought process? Tell us a little bit how it goes when you get to pick one agent. LISA HOLLE: Yeah, I think as we think about new agents that are available for each of our individual patients, we have to think about patient characteristics, I think is one big factor, such as comorbidities. For example, in the PROfound study, I think they had an instance of deep vein thrombosis and pulmonary embolism that was relatively small, but it was in the range of 4% to 7%. And so I think in a patient who might have a history of a recent PE or a thromboembolic condition, you might shy away from using olaparib if they could receive rucaparib instead. I think the prior therapies that they have received too is also really important. So both of these trials looked at patients who had advanced after receiving either enzalutamide or abiraterone. And then the TRITON study evaluating rucaparib, they also had to receive at least one taxane therapy. So I think you need to make sure that they've progressed on one of those therapies. You might try olaparib before a taxane in that patient population. PEDRO BARATA: So basically, you're saying-- because I think it's a very important message-- is not that we believe agents might be different mechanistically, right? But the way we develop drugs in the oncology world is based in the setting they were developed, right? So you're basically describing different patient characteristics that were enrolled in PROfound and TRITON, and how that led to different approval specifically regarding chemotherapy. Is that it? LISA HOLLE: Right, exactly. And so I think when you're trying to decide between two therapies that have similar outcomes, are used in a similar population, and trying to figure out which one might be better for that particular patient, I think these are some of the things that we think about. Certainly, insurance approval could be a possibility, although I would expect that insurance would cover both of these agents. They're FDA approved. They do have some different indications that we can talk about a little bit more specifically as we talk about the specific testing that's done and what mutations were found to be most beneficial from these agents. But also, I think performance status is something to consider. So when we get to later lines in therapy, sometimes, our patients have poor performance status. And as with all clinical trials, we enroll patients with good performance status. I think the PROfound trial enrolled ECOG 0 to 2, and TRITON2 enrolled 0 to 1 performance status on the ECOG scale. So again, well-performing patients. It doesn't mean that our performing patients can't receive these drugs, but they may not have the same outcomes and may have more toxicity. PEDRO BARATA: Now it's interesting that you brought up access. I don't know your experience with that. I actually had a story, and I can share now or later. LISA HOLLE: Yeah, absolutely. PEDRO BARATA: So here in our clinics, we do test everyone. And we'll talk a little bit about that in a minute. And so this patient was a BRCA, a BRCA2 positive patient. And we tried at the time, we applied for olaparib for him. And unfortunately, we were not able to get it due to insurance restrictions at the time. This was prior to the FDA approval. And so we got to be creative. And we went with a platinum-containing regiment as an alternative. And it turns out, it worked really well, as we know. I mean, there's significant data out there. But basically, demonstrating an increased activity of platinum-containing regimens for patients with DNA repair gene defects. And so anyway, so that patient did respond well. And so I think he completed-- he got some carbo plus cabazitaxel at the time. And he completed six cycles, went on observation for while, on a chemo break, as we call them. And then he progressed a few months later. And at that time, we reapplied for a PARP inhibitor. And it got approved that time, actually. So we got rid of the obstacle that we had the first time around, that we encountered the first time around. And so actually, that patient is still on olaparib and doing well. But I think that speaks a little bit to what you were saying or referring to, that sometimes, there are obstacles that we have to be aware of. And definitely, access to medication is one of them. LISA HOLLE: Yeah, absolutely. And I think this highlights a good point that we're having in all of our patients with cancer right now, is as the studies come out-- so GU ASCO was just a month ago. Data comes out and the guidelines aren't updated right away. And during that period, when we know we have an effective therapy that could be used, that's the time, I think, and even a few months after that is when we have the most difficult time with insurance approvals. And then, of course, the FDA indication also can cause a lag in insurance approvals. But certainly, I think that also shows that we can, as many of us have done, had a peer-to-peer with an insurance company to ensure that they understand the data and can approve these therapies. That's another way that we can go about that. I think one other really important thing to think about these drugs are that they're dosed twice daily. So adherence could be a problem for some patients. Most of our patients have significant comorbidities. They're older adults, have multiple medications. So it's just an additional pill burden. And as we know with targeted therapies, adherence is really important to try to prevent the resistance that will ultimately develop, but try to prevent it from happening sooner. PEDRO BARATA: Right. LISA HOLLE: So I guess we probably should talk a little bit more about the testing that needs to be done and how we go about testing our patients. So could you share your experience with that, Dr. Barata? PEDRO BARATA: Yeah, for sure. I mean, that's truly, truly important. And thank you for highlighting that again. So as I was referring to earlier today, there are two types of testing, right? Germline and somatic testing. So the germline can be done with, for example, a simple blood test. And there's a bunch of commercially available assays that can do that for us. In regard to somatic testing, we can do it in the tissue. We can use a fresh biopsy or archival tissue, or we can do a liquid biopsy where we basically find circulating tumor DNA that's at the time of-- it's also a blood drawn, basically. So in prostate cancer world-- and I think that that's familiar to a lot of folks who treat prostate cancer-- they do know a lot of times, archival tissue is available from many, many, many years ago. And a lot of times, we cannot get fresh tissue or tissue that we feel represents the reality of the tumor today when we have the patient coming in to see us, for example, right? So I guess access to tissue is often a problem. And as you were saying, Lisa, both PROfound and Triton and other really biomarker positive studies, they often start based on tissue, not based on liquid biopsy, right? So the question is, in the absence of tissue, what can we do? And there's an emergent number of studies have shown good concordance between liquid biopsy and tissue. So I'll tell you what I do. We do favor tissue sequencing. And there's also a number of commercially available assays out there. And when I don't have tissue available and I really think we should do somatic testing, I use the liquid biopsy as a surrogate, if you will. It's not perfect, right? Because unless the tissue and liquid biopsy are kind of collected around the same time, and even though the panels are different-- so there are all these differences in there. But I think if we find, in this case, a gene defect with a good allele fraction, at least in my experience, I had that a few times. I did not encounter obstacles to access to a PARP inhibitor. But I still favor tissue because that's where the data was developed. And so that's just my style, right? I try be data driven as much as possible in all germline, right? If I have a germline that more than likely is going to be the tumor, right? Because all the cells wouldn't have it, but not necessarily. But anyhow, if I have a germline test positive or tissue positive, I'll use it. If I don't have tissue and I have liquid biopsy, I would still try it. But that's kind of my go-to, right? Now I do-- based on my conversations with my colleagues from the community, there's a little bit of concern about what to do with the results, meaning if you don't test, you don't know. But if you test and something positive comes back, you need to sit down with your patient or at least provide some kind of explanation and understanding. And some of us more than others are a little bit less familiar with some of the genomic alterations we can find. And I don't know all of them, to be honest. And they can create a challenge. So sometimes, we don't test because concern about the results. I would like just to highlight the fact that these commercially available assays, they do a good job, even a better job now than before, in terms of providing genetic counseling sometimes online or over the phone. And actually, some of my patients have used that in addition to just kind of go through the results with me. So that's something to be aware and it's simple to do, right? And we talked a little bit about reimbursement, especially before the approval. So approvals is based on the setting, right? So if I want to do, for example, rucaparib to patients who did not get chemotherapy, it can happen that insurance will, the payer will say, this patient needs to receive chemotherapy first. Because that's based on how TRITON was designed, right? And so you have an alternative, which would be olaparib, that doesn't require prior chemotherapy. And that doesn't speak anything, as you said, regarding which agent is best. And I'll defer, you did a great job in terms of breaking down in terms of safety profiles and the differences. But my point is, knowing where the medication was developed helps when we ask for that therapy for our patients, right? And then, the last point I would like to make is in addition to the therapeutic implications, especially germline testing, I think it's important to be aware of the familiar implications. And so, some way or the other, germline assays, test assays do provide support for family members to get tested. So here in clinic when we test them, basically, family members get tested for free if the patient is positive and as long as the patient agrees with it. Because he's actually the one who provides us the information to reach out to family members. And so I'm just thinking an example where we found a patient who happened to be BRCA1. And then we were able to go after his family and test his family. And we found another two positive cases. And two females, one in the 40's, one in the 30's, I believe. And so I actually think we did change the future for those two individuals. So the implications that go beyond the patient in front of us are actually huge. I have another case in kidney with a genomic operation, where we have, since this patient was diagnosed-- and it's not a kidney cancer conversation-- but since this patient was diagnosed, three others developed cancer. And we found another four patients who harbored that genomic alteration. In that case, it was a path one. But I'm just sharing the potential implications for family, which I think is huge. Because our care goes beyond the patient in front of us, right? And sometimes, it can impact what we do with the family. So that's-- so the bottom line, to me, is if we don't test, we don't find. It's OK not to know everything about the test results. And there's more resources out there that can help us with that. And the implications of testing are significant. LISA HOLLE: You make an excellent point on those things. The other question I had for you is, you know, I think the guidance right now is that we do somatic testing at the time of development of metastatic castrate-resistant disease. But there is also some suggestion that we should repeat that somatic testing when somebody progresses after a treatment, right? So do you do that routinely? PEDRO BARATA: Yeah, that's a great question. That's a great question. And obviously, I'm biased because we do research in addition to standard of care approach. So I have to say, what I do, and here at Tulane, we basically test everyone for germline at time they step in the clinic with metastatic disease. We have the discussion for recurrent disease no mets, and then for high risk as well. So that's in regards to as far as germline testing goes. In terms of somatic testing, I also had one upfront. The reason why I get, if I have tissue and I'll use a tissue if I don't. I do liquid biopsy before I start them on systemic therapy. The reason why I do that is because it helps me to plan. And I think as one of my former mentors used to tell me, I guess, was that as an oncologist, we always like to anticipate. And we always have a plan B. And I love anticipate. I hate surprises. I only like surprises at home. I don't like them at the office. And so having that information allows me to plan things when option A won't work for them. So a lot of times, I get the testing here back. And I'm not even doing anything with it in terms of PARP inhibitor, for example, right? Because to your point, they are approved in the metastatic castration-resistant setting. And a lot of times, they do it for castration-sensitive settings. So what do I do afterwards? Well, that goes a little bit in the research side. We do a lot of serial sequencing, tumor sequencing, if you will. Germline, we only do it once. And the reason for that is we do see changes over time, meaning exposure to treatments has the ability to impact the molecular phenotype or the molecular makeup of the tumor. So that's the reason why we do it. Does that happen a lot? I don't think, or at least that it's targetable, the answer, I don't think it is. But for me, we published something about MMR/MSI, where we were show that MSI might be acquired over time. It goes beyond the germline. And so as an example, if I find one additional patient that is able to get benefit from a target therapy or immunotherapy that would not otherwise, and would never offer him the therapy, to me, that's a lot. That's very significant for that patient in front of me. So having that repeated, it's important in that perspective. It's not ready for primetime in my opinion. I think we should. If we can, I think we should do it. But right now, the data is still lacking. The strong data is still lacking to provide guidance in terms of how often should we be testing these patients and when, right? And after what therapies? So those questions remain unanswered, which are very important questions. I just say, if you have the ability to do it, why not do it? And so, Lisa, so it's kind of a good segue way to the next portion of it, which has to do-- we talk a lot about olaparib, rucaparib, similarities, differences. Can you basically expand a little bit about how do you choose them, and a little bit about the approvals, how that impacts your treatment decision? I know you talk a little bit about it. But can you highlight us on the safety profile and toxicity a little bit more? LISA HOLLE: Sure. So you know, just to recap, the olaparib, which was evaluated in a PROfound study, looked at homologous recombinant repair gene mutations. So it sort looked at a broader group of mutations and had most benefit in BRCA1, BRCA2, and ATM, although some of the other mutations also had some benefit, and was studied after progression on enzalutamide and abiraterone. So that's what its indication is for. Rucaparib is indicated for patients who have a BRCA mutation, germline or somatic, who progress after abiraterone or enzalutamide and at least one taxane. So that's sort of the difference in terms of the indications and how they were studied. As I mentioned, they both had good performance status patients. So we have to sort of think about that again when we're thinking about overall use of these drugs. But in terms of differences, some of the key things that we think about are potential for drug interactions. As I said, many of these patients are on a lot of different medications. Rucaparib has several different cytochrome P450 interactions that can occur. So it has more potential for drug interactions than olaparib does. Olaparib needs to be dose adjusted for patients who have renal dysfunction, has that incidence of VTE that was higher than the comparative arm in the PROfound study. So that's something to consider. And then, I think with olaparib, there are some other laboratory abnormalities that we don't tend to see with olaparib. So with rucaparib, we can see LFT elevation, elevations in triglycerides, alkaline phosphatase, so just something to be aware of. It doesn't often require a necessitation of discontinuation of the drug, but can happen and also is associated with a rash. So those are some of the differences between the drugs. PEDRO BARATA: Yeah, that's a great review. In clinical practice, and I know you've used both, right, anything that you think differently? Like, when you have a patient on olaparib or a patient on rucaparib, is anything that is a red flag for you, or at least, like, rings a bell and say, hey, should be thinking about this? You know, tells us what you're thinking? LISA HOLLE: I mean, one thing that for those providers who work with multiple tumor types, so we use these drugs in ovarian cancer patients, obviously. And in that population, there actually is the risk of developing myelodysplastic syndrome or acute myelogenous leukemia. And so far, at least with the data that we have in the PROfound and the TRITON studies, we didn't have any incidence of that reported to date, even though these patients had received potentially some other chemotherapy agents that could put them at risk. So I think, if you use these drugs in other settings, that might be something that you're concerned about but we haven't seen in the prostate cancer population. And then, I think we do see cytopenias that can occur just as a result of the mechanism of drug. And we have to monitor the complete blood count with differential in these patients. But I think as oncologists, we're very familiar with managing these patients. They often don't need dose adjustments or discontinuation due to cytopenias that are relatively mild. They also can cause nausea. So we just have to make sure our patients have an antiemetic at home. And we continue to make sure that they're benefiting from either using that or understanding that that doesn't necessitate skipping the drug because they're not feeling well. So it just requires some sort of monitoring of those patients. I think those are the biggest things that we tend to see in our patient population. PEDRO BARATA: Yeah, no, that's good. And you remind me that those are very important points safety-wise. I was thinking, if I have a patient in front of me that has not received chemotherapy, for example, and he's now progressing on abira/enza, right? And let me say, because I just got a patient like that recently. And so when would be the time when I would probably not choose a PARP inhibitor and I would choose something else, right? And so, as we learn a little bit more about the different homologous recombination gene defects, we start to understand that not all the dose defects are the same or mean the same in terms of what we expect from these therapies. And so I was thinking of a case where just based on the genetic information he had, so we basically came for a trial second opinion. He actually was-- he couldn't make the trials. But he happened to harbor a CDK12, which is approved, by the way. If we look at PROfound, right? As you mentioned, this would be a patient-- we actually had a report, when I got the report back. And he was reading the report. Good, Doc, I'm going to get a PARP inhibitor, because they were there, right? He said CDK12 benefit PARP. And I was actually not convinced that would be the best option for him. And I'll tell you why. I mean, he actually was symptomatic. And I basically showed him the breakdown of the PROfound data that basically suggests minimal activity of a PARP inhibitor for those patients, for example, right? Which is a little bit interesting to be in clinic with a piece of paper saying you're going to benefit from something. And the physician might be telling you, well, let's not go so fast, right? And this is why. And I pulled PROfound. I told him the story about TRITON. They had a CDK12 cohort that was discontinued due to lack of activity. And so I end up-- I plot for him a different approach, a chemotherapy approach would be a better choice for him. And I did not go with the PARP inhibitor. And I think, to me, as we learn more about what the different genomic alterations do mean and what we expect with them, I think we're going to have these discussions more and more, meaning it's not like, oh, you have a checklist of homologous recombinations in the facts. You should get the pill. I think the discussion goes beyond that and it takes into consideration several different factors. I just gave an example about the type of gene, but also what you just said in regards to safety, in regards to patient comorbidities. And so this is a great option in my eyes. It's a fantastic option, actually. We have survival data now from PROfound as well, right? It makes them live longer. It prolongs time to progression. And so it's definitely a huge advantage that we got in the prostate cancer world, one of the recent developments that are truly meaningful to patients. But I don't think it's still applicable to all of them, right? And so I'm just-- as you were talking about safety, et cetera, I just remind myself of that case because it reminds me, not all genomic alterations mean the same. And speaking of that, it will be interesting to see. One of the things that are coming up in the future is we do have these broad studies that test PARP inhibitors for unselected group of patients regardless of their molecular phenotype, right? So that will be, to me, that's a very interesting group of trials. Because we don't know whether or not it's going to be-- we're going to see an advantage there. But I think it's very interesting to explore that concept because it would take us beyond a select group of patients based on the biomarker to a more broader application and use of those therapies in an advanced prostate cancer arena. I don't know your thoughts about that, Lisa, and whether or not you want to share other thoughts about what's coming up. LISA HOLLE: No, I think that's an excellent point. And it'll be very interesting to see the results of those trials. Before we talk about some of the other things that would be interesting and what we hope to see from these drugs, it reminded me when you were talking about that patient who you chose not to use a PARP inhibitor, even though they had a HRR mutation. Do you, in your clinic, allow for more time in those conversations where you have to go over the results of their sequencing? PEDRO BARATA: Yeah, great question. So because I do it in advance, right, I do it and I do it over time. So yes, the answer is yes. We go over the genetic information over and over again. And that's one of the reasons why I do it as soon as I meet with the patient because it allows me-- I don't expect this information to be well-captured the first time. It's very complicated. And sometimes, we still struggle ourselves in understanding exactly that what that means. And so repetition is very helpful, and to go over the data and just explain the data differently. And so that, I mean, that happens a lot with me. So I do know, I have a number of patients who have constriction-sensitive, who I know they harbor BRCA or whatever, CDK12 or something else. And I do bring it up to our meetings, right? I do say, listen. It is great. This is working great for you. Remember, we have this genomic alteration that does this. And this opens the door to more options in the future, et cetera. So I try to remind the patient and myself of that over and over, so that if we have to use that information, he's already familiar with it. I hate to chase the tumor. I hate to be behind a cancer. Like, you know that feeling when the tumor is progressing, you're chasing the cancer to regain control of the disease, right? So I like to, or try to at least be one or two steps ahead, anticipating what might happen, right? And there's a lot of factors that help us to do that. But certainly, testing them early helps us to accomplish that. So that's something that I do. And it helps me as well to be more comfortable in clinic. LISA HOLLE: Yeah, we do a similar thing in our clinic. I think it's really beneficial to do that because I think patients sometimes hear about precision medicine. And they feel like if they have this super medication that matches their tumor, that's going to be the silver bullet to their treatment, right? And that, I think, is something that we have to often play down and explain what this really means, and that this is something that can be used later on and isn't quite as magical as they think it might be. So I think that's a good way to do it. I think one of the things that we don't know, and this is true of most targeted agents, like if you fail one PARP inhibitor, can you have a benefit from the other PARP inhibitor? Or should we use a platinum-based therapy first before a PARP inhibitor? And I think those questions are interesting and yet to be answered. PEDRO BARATA: Yeah, that's a great point, right? I mean, I have the feeling that they might not work the same way, right? And so we don't have data so far that categorically shows us that one PARP after the other would work. However, we can look at our friends from other tumor types and see that that approach has not been followed. And so I wouldn't expect that to be the case. In regards to platinum and PARP, that's a different story. I can see in the future, patients receiving platinum after PARP inhibitors and not the other way around. I mean, the other way around probably would happen if there's some difficulty with access to the PARP therapies. But we tend to use novel therapies more than the old ones, right? And platinum has been around for so long. And it's still a great therapy, especially combination, right? Because we now have got a piece of data we have the data from Houston group with cabazitaxel combined with carboplatin, right? Which was published about two years ago. And so I do think, I have to say, I'm biased because we're doing a little bit of research on that. I know data will come up to answer that question will be better, real world data in terms of activity of platinum post-PARP activity of PARP plus platinum. And we'll see that data more and more over time. But you're right. We don't know the answer for sure. And I'll be honest. Until I know it's definitely a no, I'm probably going to try if I don't have another option, right? So that's how we come up with those cases. And then we try to put them together and report their outcomes. And that's one kind of question that's out there. There's still an answer, to your point. Another one would obviously be we keep talking about PARP inhibitors. That's how great they are. And they got approved in their specific setting. The question is, are they still benefiting patients in different settings? Like, hormone testing, for example or unselected group of patients, as we talked about earlier. And those type of questions remain unanswered. I do know they will get data that will help us to answer those questions. But that's definitely something that we'll pay attention to as we move forward. And finally, combination regimens are being tested with different PARP inhibitors, including radium, including immunotherapy, chemotherapy, et cetera. So novel and monotherapies, I do think that it will be very interesting to see whether or not throw the sink with a PARP inhibitor in there versus sequencing the different therapies that we have available provides a different advantage to patients. What are your thoughts, Lisa? LISA HOLLE: Yeah, no, I think all of those things are considerations that are likely to have answers in the relatively near future as we get through those studies. I think it's interesting to think, like, is there a group of patients who don't have metastatic disease, probably, who have these germline mutations that could maybe benefit from a PARP inhibitor very early in treatment so that they don't progress to metastatic disease? But that obviously is quite far in the future in terms of where we might have these drugs, but not something that we should consider and evaluate at some point. I think novel other PARP inhibitors, I'm not aware right now of things advancing quite quickly in that area, but that's another area where we might have new agents that could have similar mechanisms of action that could be useful as well. PEDRO BARATA: Right. No, that's great. That's a great point that you bring, thinking about the non-metastatic space, right? I feel like today, we've been talking a lot about metastatic in this setting. But you're absolutely correct. There might be an impact in the non-metastatic setting as well. No, I mean, I think this was a great conversation. It's always a pleasure to talk to you about any topic, really. But it was great talk about prostate cancer. Let me ask you, Lisa, do you have any final take-home points for folks who might be on the other side hearing us? LISA HOLLE: Yeah, I think the biggest thing is that this is an exciting new era, right, in this metastatic castrate-resistant setting, and that we need to be mindful of the data that's coming forward. So we have just recently, the overall survival data published from PROfound and updates that continually come out. So I think it's important just to stay up-to-date with this information to make sure that you're aware of the toxicities of these new drugs as we continue to use them. And don't be afraid to have those conversations with patients about how this might be something that could be part of their therapy in the future, but have those conversations early. PEDRO BARATA: Yeah, no, that's great summary points. For me, I would love to highlight the importance of testing. And I think we covered it. The safety, no less, that you did a great job at telling me and the folks out there about it. And exactly what you just said, what's coming up in the future. And these are, for sure, great, great news for patients who, unfortunately, were diagnosed with advanced prostate cancer. All right, well, Lisa, it was a pleasure talking to you today. And thank you for ASCO for putting this program together and allowing us to discuss a little bit about PARP inhibitors in prostate cancer. So thank you. And have a good day. LISA HOLLE: Yeah, thanks, Dr. Barata and ASCO. This was a great conversation. Thanks. PEDRO BARATA: Thank you. [MUSIC PLAYING] ANNOUNCER: Thank you for listening to this week's episode of the ASCO e-learning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

Get the inside scoop on major immunotherapy breakthroughs in esophageal and gastroesophageal junction (GEJ) cancers. Drs. Ronan J. Kelly (Medical Oncologist, Baylor University Medical Center) and Jacob Kettle (Pharmacist, University of Missouri) discuss recent practice-changing clinical trials, new drug approvals, and their application in practice. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: elearning.asco.org | Contact Us (Air date: 4/21/2021)   TRANSCRIPT [MUSIC PLAYING]   ANNOUNCER: The purpose of this podcast is to educate and inform. This is not a substitute for 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. [MUSIC PLAYING]   JACOB KETTLE: Welcome to the ASCO e-learning podcast episode focusing on immunotherapy for esophageal and gastroesophageal junction cancer. My name is Dr. Jacob Kettle. I'm an oncology clinical pharmacy specialist and pharmacy manager at the University of Missouri Health Care's Fischel Cancer Center. Today, I'm joined by medical oncologist, Dr. Ronan Kelly. Dr. Kelly is the director of oncology at the Charles A. Sammons Cancer Center and the WW Caruth junior chair in immunology at Baylor University Medical Center in Dallas. We have a lot of great content to explore today, so really, some things that are truly practice-changing. But to facilitate learning, let's start with a brief patient case. SB is a 64-year-old male who initially presented to his primary care physician with a two month history of dysphagia with solids, unintentional weight loss of 25 pounds, and fatigue. Endoscopy revealed a tumor in the distant third of the esophagus and pathology confirmed an invasive moderately differentiated adenocarcinoma. Preoperative workup patient was stage II. Following chemotherapy and radiation, esophagectomy demonstrated 5 of 20 lymph nodes positive. So while we're going to focus predominantly today on the role of adjuvant therapy with immunotherapy treatments in esophageal and GE junction tumors, to truly appreciate these advancements, I think it first requires understanding the challenges of the disease state. So Dr. Kelly, would you mind summarizing the historical treatment landscape and how there's been such substantial unmet needs in this patient population? RONAN KELLY: Sure. And thank you, Dr. Kettle, and thank you to the ASCO team for the invitation to participate in this podcast today. If we look at esophageal and gastroesophageal junction cancers, there really hasn't been that many breakthroughs in recent years. We've really been relying on two major ways to treat stage II and stage III disease. And we're going to talk about operable disease for the first part of this podcast. At the present time, the standard of care had been either chemoradiation with the cross regimen, which was published by van Hagen and Allen in 2012, so almost 10 years ago now. And there has been concern about the use of low dose chemotherapy with that regimen. People have wondered about the need for really systemic doses of chemotherapy. It's very well-tolerated, but again, the concern was, are we minimizing the systemic treatments using chemoradiation? However, that really had been the favored regimen for many years. In the last couple of years, we've probably seen people moving away from low dose carboplatin/paclitaxel into more of a FOLFOX type regimen with radiation, and then having the surgery. The other way to do this is perioperative chemotherapy, which really, the current standard had been the FLOT4 regimen. This was a regimen that emerged from Germany, published in 2019, using chemotherapy for four cycles before surgery and four cycles after surgery. There is a challenge there, however. The FLOT regimen is mostly, if you look at the study design, was predominantly a gastric cancer with 44% gastric cancers, 33% GE junction. IRC were 2 and 3. And then, 23% being Siewert type 1, which is, they didn't have any esophageal patients per se in this study. But the challenge with the FLOT regimen is less than half of patients can actually complete the post-operative chemotherapy once they've had surgery. It's only 46%. And of that, you do see quite significant grade 3/4 neutropenias. Approximately half the patients get that with 18% getting grade 3/4 infections, 35% needing GCSF support. So we really needed to see if there was something we could do after chemoradiation rather than just chemotherapy alone. And so that was really the reason why we were looking to see if we could maybe introduce an immunotherapeutic strategy into that adjuvant setting. And that was the design of the CheckMate 577 study, which I know we'll talk about in a few minutes. JACOB KETTLE: Yeah, perfect. I think it definitely characterizes, as a disease state, one that is very challenging. And kind of despite our best intentions and efforts, as historically, we just-- patients inevitably relapse, at least around 50% or so. Would you say it's a fairly accurate characterization of the problem? RONAN KELLY: Yeah. If you look at the five year overall survival rates as well, we're really-- what we know is that if you have a pathologic complete response to chemoradiation, you really can do quite well. The five year overall survival is the order of approximately 50%. But if you're not in that, and the majority of patients are not in that, 70% to 75% of our patients do not achieve a pathologic complete response to neoadjuvant chemoradiation. And we have known that those patients do poorly. The problem is, we haven't really had any large prospective randomized phase III studies. Also, we haven't had a global study to show us how poorly those patients do. And so the CheckMate 577 study was probably the first one, truly a global study done all around the world, which was able to enroll different patients, different histologies, different racial backgrounds, to really help answer that question. JACOB KETTLE: Perfect. So I think one of the most fascinating things in oncology practice, really, across the board, is to watch how checkpoint inhibitors have really transformed the landscape of so many different tumor types. And we've seen this migration where these drugs presented first in the second, third latter line metastatic space, and migrated to first line metastatic space. And now we're starting in several disease states to see them to move into the adjuvant therapy. And that, as Dr. Kelly has already alluded to, is kind of the principle behind CheckMate 577. It's looking at-- it's really one of the first large randomized control phase III trials to explore neoadjuvant immunotherapy in the setting of esophageal and gastroesophageal cancer. So Dr. Kelly, if you wouldn't mind, spend a little more time summarizing the trial design in the patient population and CheckMate 577. RONAN KELLY: As you know, we have seven checkpoint inhibitors approved in the metastatic setting for multiple different cancers. But as you mentioned, now they're starting to move into earlier stage diseases. The only approval right now for a solid tumor in the adjuvant setting is in melanoma. We have seen positive studies there with nivolumab and pembrolizumab in CheckMate 238 and KEYNOTE 054. But that's when standing alone on its own. We've known melanoma as kind of an outlier, if you will, exquisitely responsive to checkpoint inhibition. So then, along came this, gastroesophageal junction study, the CheckMate 577. Really, in my mind, breaking the mold, almost introducing a new era because we've now seen positive results in another adjuvant setting. So I said it was a global phase III randomized double blind placebo-controlled trial. Patients were eligible if they had stage II or III esophageal cancer or gastroesophageal junction cancer, did not enroll gastric cancer patients on this study. They could either have adenocarcinoma or squamous cell carcinoma. All patients had to have that neoadjuvant chemoradiation followed by surgery. They couldn't be treated with just chemotherapy alone. They had to have the chemoradiation. And they had to have an R0 resection. And then once they recovered from their surgery, we gave them a window from 4 to 16 weeks to recover. Remember, an esophagectomy is a very large oncologic procedure to have to recover from. So many patients did need that 12 weeks upwards to recover from having their esophagus removed. Every patient had to have residual pathologic disease. So they had to have greater than YPT1 1 or greater than YPN1. So we excluded those patients, the 20% to 25% that have a really great response to chemoradiation. So we took out all the patients with, if you will, the best biology in terms of the great responders to chemo/rads. And we took the really poor responders, the other 70% to 75%, and said, what can we do in those patients who haven't achieved a path CR. Can we help them rather than just watch and see when their tumor occurs? And so that was the design of the study. We randomized, in a 2 to 1 manner, 794 patients with 532 getting nivolumab, 262 getting placebo, which is the current standard of care because there was no role for additional treatment at that time. And the primary endpoint that we've presented so far was disease-free survival. The secondary endpoint is overall survival. We don't have that data yet. It's ongoing. But we presented median follow-up data at ESMO in 2020 at the plenary session. We presented this data. And the median follow-up was 24.4 months. And so that was really the design of the study. As I said, geographical regions that enrolled, we had 38% from Europe, 32% from US and Canada, 13% Asia, and 16% rest of the world. And if you look at the practice-changing studies that have really driven our current standards of care, they've all emerged from single countries like the UK or Holland or Germany or Japan. We haven't really had a global study like CheckMate 577 at this early stage operable disease study, which I believe has changed the practice of care. JACOB KETTLE: So I think actually, too, as a pharmacist, one of the things that I thought was unique about the trial design was the nivolumab dosing schedule, 240 milligrams every two weeks for 16 weeks, or eight total treatments, and then 480 milligrams every four weeks for up to a year. And I think this is the first time, at least that I'm aware of, we've seen kind of an explicitly described induction-type maintenance plan with nivolumab. And I think, kind of been urging our practice to do something similar to this for some time. So it was kind of exciting to see it prescribed out in that fashion. Because it really fits with the adverse effect and monitoring profile of these drugs. You kind of, in that first 16 week period where the colitis, hepatitis type effects are more common, you're seeing the patient more often. You have more frequent therapies. And then you kind of draw things out when they cross that threshold. So I thought that was one thing. Again, with my background in pharmacy, I thought that was unique about the trial design. That was specific. So I know everyone's waiting to hear it. What were the key outcomes from this study? RONAN KELLY: Well, if you look at the patients that we enroll, as I said, it was a 2 to 1 randomization. In terms of the tumor location, 60% for esophageal cancer, 40% for gastroesophageal junction cancer. In terms of histology, the breakdown, because again, certainly, in Europe and in Asia, adenocarcinoma is the more common subtype than squamous. We saw 71% of patients had adenocarcinoma. We had 29% having squamous cell. And then the disease stage was 66% had the more advanced stage III disease at the start, 34 had stage II. And then, so if you look at the overall tolerance, the treatment was really well-tolerated. And we may come to that. But 89% of the patients received a dose intensity of greater than 90%, which really is great for an adjuvant study. But if you look at the primary endpoint, which was the disease-free survival, we doubled the disease-free survival from the placebo arm to the nivolumab arm. The median disease-free survival was 11 months in the placebo arm and 22.4 months in the nivolumab arm. This had a hazard ratio of 0.69, p-value of 0.0003. So overall, nivolumab provided a 31% reduction in the risk of recurrence or death, and as I said, a doubling in the median disease-free survival. And if you look at the Kaplan-Meier curves, there's clear separation of the curves. And you can see how poorly those patients who were just being observed to 11 months with disease-free survival. And we know, unfortunately, disease-free survival is a pretty good surrogate for overall survival in this setting. So, you know, I think, I hope that the days of just watching someone who has gotten lymph node positive disease on surgical pathology report may be coming to an end, I hope. JACOB KETTLE: Yeah, I think we'll all be anxiously waiting on the overall survival data to mature. But this is remarkable, that degree of an improvement in this population that, as you've said, really, we desperately needed to find new avenues to serve them and improve their outcomes. That's outstanding. I know the data is early and I'm curious if you have any indications of impact of histology or biomarkers. Or do you feel like the benefit's going to be fairly universal? Or maybe it's too soon to tell. RONAN KELLY: No. So in the data that we present, everyone was actually expecting squamous cell to do much better because we just know squamous histology is doing better with esophageal and esophagogastric cancers. If you look here, we did see a benefit from squamous over adenocarcinoma. But the median disease-free survival in adenocarcinoma group versus placebo was 19.4 months versus 11.1% months. That was a hazard ratio of 0.75. If you look at the squamous cell histology, yes, it was better. It was 29.7 months versus 11 months. And that had a hazard ratio of 0.61. But we were very excited to see that benefit in the adenocarcinoma setting because we see that really shows proof that there's efficacy there. We didn't see any major difference in terms of lymph node status. We saw some, if you were greater than YPN1, we saw hazard ratio of 0.67. We measure tumor cell PD-L1 expression, and that's all we've been able to report so far. We did not see tumor cell PD-L1 expression greater than 1% having an impact. What I will say is Dr. Kettle, the manuscript is hopefully coming out soon. And we were asked to do post-hoc analysis looking at CPS. So that data will be in the manuscript. JACOB KETTLE: Yeah. That's outstanding and exciting, for sure. Nonetheless, this is more therapy. And you are going to be exposing patients to more potential to adverse events. Are there any patients who you would not consider a candidate for this treatment? RONAN KELLY: Dr. Kettle, if we just look at the treatment-related adverse events with potential immunologic etiology, because that's really the one you're trying to see is the nivolumab causing some immune adverse events, really didn't see that many. The majority of TRAs were grade 1 or grade 2. Those that were grade 3 or 4 occurred in less than 1% of patients in the nivolumab arm. And there was no grade 5 treatment-related immunologic adverse events. And as I said, we were worried at the start-- not worried, but we were concerned, would we see pneumonitis? Because, as you remember, we've given chemoradiation to these patients. And we haven't really had any data when we were designing this study on how effective PD-1 inhibitors would be in early stage diseases. So it was very gratifying to see that very low incidence of pneumonitis. If you compare it to the placebo arm, we saw 0.8% pneumonitis in the treatment arm, and 0.4% in the placebo arm, so very good. And then, if you look at the tolerability of the quality of life data, really, measured by all of the patient reported outcomes that we use, we saw very similar overall health status between the nivolumab and placebo arm. Is there anyone you wouldn't give this to? Well, of course, the usual patients that are contraindicated for a checkpoint inhibitor, like severe autoimmune disease. Patients who would not be eligible for this are patients who haven't had the standard design, like I told you about. This was post-chemoradiation. So we don't have data yet if you just give perioperative chemotherapy and don't use radiation. We're waiting on one of those studies. That's KEYNOTE 585, to answer that question. So we can't just start using this for all patients with early stage disease, just those patients who got chemoradiation followed by surgery and if they haven't had a complete pathologic response. It's already actually made its way into the NCCN guidelines. So I know that happened in December of 2020. So doctors in the US have started taking this up. It was given category 1 evidence by the committee, so I know a lot of people around the country are already using this as their new standard. JACOB KETTLE: Yeah. I'm actually really glad you brought up the quality of life data. Because I think, to me, as we start having more treatment options available, I think it becomes increasingly important that we, as clinicians, remain sensitive to patient values and what they experience. And seeing that quality of life data, which was, I think I saw it was published online in January in JCO. But really shows that very equivalent addition of nivolumab to these patients did not diminish their health-related quality of life compared to placebo. And I think that really highlights the fact that we've got a very positive risk-to-benefit ratio with this therapy. And I think it just underscores what a remarkable improvement this is to add to our arsenal for patient care. I do want to circle back briefly, then, to our patient case. So Dr. Kelly, in your opinion, what would be the best therapy, the optimum treatment for that hypothetical patient we discussed moments ago? RONAN KELLY: So assuming there's no contraindications to a PD-1 inhibitor, then in my opinion, the new standard of care is someone who has lymph node positive disease like you mentioned would be. Rather than just watching them with close observation, it would be adjuvant nivolumab for a year. Now as I said, not everyone made it through the whole year. But 89% of patients had greater than 90% of the dose intensity. So it shows that it's well-tolerated. When is the optimal time to start? Again, what we looked at-- and this data may come out in our manuscript. We looked at less than 10 weeks after surgery versus greater than 10 weeks. So we'll see that in the manuscript. But I think people can really start whenever the patient feels like they've regained their strength after their oncologic operation. JACOB KETTLE: Excellent, so I think that's going to summarize where we wanted to talk about for adjuvant care. I think, let's move forward and talk just briefly about in the metastatic setting, and kind of the role of immunotherapy there. So I'm going to present another hypothetical patient case. That one is CJ. This is a 61-year-old female with a previous history of gastroesophageal junction cancer, for which she completed trial modality therapy approximately two years ago. No previous treatment with immunotherapy for that. On follow-up, she notes recurrence of progressive dysphagia. The CT revealed a mass in the gastroesophageal wall, liver, and adrenal gland. These were all confirmed via biopsy to be recurrence of the original squamous cell cancer. Her combined positive score was 15. Her ECOG performance status currently is zero. And so, again, as we start to see these new options as you said, likely established a new standard of care in the adjuvant setting, the reality is, we're going to continue to see patients in the metastatic setting, whether it be those diagnosed before the availability of checkpoint inhibitors in that space, or those who were just diagnosed in later stage disease. So I think it's worth discussing. Amidst all the other options we have, what's the role, Dr. Kelly, at least, the current state for immunotherapy in those with relapsed or metastatic disease? RONAN KELLY: Yeah, it's a great question. Thank you. I think 2020 will go down as an amazing year for esophageal and gastric cancer because we saw so many phase III studies being presented towards the latter part of the year, which I think everyone has accepted they've changed practice. They all came out at the same time. As you know, we had a plenary session at this year's ESMO, specifically just all around gastric and esophageal cancer, which never happened before. But at that meeting, in addition to CheckMate 577, which we've spoken about, we saw two additional ones that I believe in the metastatic setting have changed practice. We saw CheckMate 649, which is nivolumab plus chemotherapy, which really broke the barrier for that one year overall survival in the metastatic setting. If you look at the primary endpoint of that study was overall survival in patients with CPS, PD-L1 expression greater than 5. And the endpoint there was 14.4 months for the novel treatment arm versus 11.1% months for the standard chemotherapy arm, hazard ratio of 0.71. So really, a groundbreaking result because we've been struggling to break through that 12 month overall survival barrier. And that also has now been put into the NCCN guidelines as of December as well, 2020. So I think that was given category 1 evidence also. And we're waiting for FDA approval for all of these things. We hope that that will come in the middle part of the year. But the NCCN has kind of already put them into the practice guidelines. And then the other one in my mind, which changed practices, Dr. Kettle, is KEYNOTE 590. This was involving pembrolizumab plus cisplatin 5FU. It was more of an esophageal rather than a gastric study. And here, again, they looked at chemotherapy versus chemotherapy plus pembrolizumab. And we saw, again, if you look at the CPS greater than 10 population, 13.5 months versus 9.4 months, hazard ratio there is 0.62. If you look at just all patients rather than selecting by CPS, the overall survival rate was 12.4 months versus 9.8 months, hazard ratio 0.73. So I know you're going to talk a little bit about the role of these biomarkers and selecting patient according to CPS. But we're beginning to see that in these studies now. It's getting quite complicated, I would say. Let's wait for the FDA approval. Let's see what the FDA say if they put some stringent guidelines around what the CPS cutoff should be for those metastatic studies. But I would love to hear your opinion on where you see that going. JACOB KETTLE: Yeah. I think you said it. The role of biomarkers is, by far, going to be the most complex piece of this whole puzzle moving forward. And I think a lot of this won't translate very well via audio. But one great example is our studies with single agent pembrolizumab in the second line setting. The current guidelines suggest a CPS score greater than 10 to be able to use pembrolizumab in that space versus a CPS score greater than just 1 for third line or subsequent settings. And there's all kinds of other little caveats out there with different agents and nivolumab versus pembrolizumab, and whether we're combining them with other treatments or using single agent. Then, of course, we have tumor mutation burden, microsatellite instability all in this mix. And I think what's challenging, truly, is for clinicians like myself, I don't really have a very strong background in a lot of this immunology. So it's tough to wrap your head around how to apply these things and operationalize it into your patient care when it seems like there's new guidance and differences and things like that. I don't know that I'm versed enough to have a really strong opinion over which biomarker is preferential. So I actually was curious for you, Dr. Kelly. Where do you gravitate towards and where do you see-- what biomarkers do you see shaking out in the future? RONAN KELLY: Yeah. You know, it's really fascinating. I think we look at this as a very exciting time, probably, some of the most exciting time we've ever had in gastroesophageal and gastric cancer. Because we're now seeing real movement, right? We're seeing tremendous benefits moving forward. But we still have a long way to go where we cannot rest on our laurels here. But if you were to say, what are the biomarkers that people would check in 2021 when someone walks in the door in their clinic? Obviously, PD-L1 status should be done reflexly. We believe CPS score is a better way to do that. So the pathologists are getting used to doing CPS score and giving us the breakdown, whether it's greater than 1%, greater than 5%, greater than 10%. In addition to that, microsatellite instability mismatch repair deficiency should be checked, especially in gastric gastroesophageal junction. Because you don't want to miss that if that is there, because those patients can have, really, a dramatic response. And the FDA approval there is around pembrolizumab. And then we've also seen an approval for TMB high, or tumor mutation burden high greater than 10 mutations per megabase again for pembrolizumab. So that can be something doctors can keep in their armamentarium if they're checking for TMB. And so that's really where we are. HER2 status is always present, of course. We've seen some really nice breakthroughs this year in the HER2 story with trastuzumab/deruxtecan being approved in the second line setting for those patients who are HER2 positive. So it's been a great year, absolutely. I know it's complicated with all the different CPS, but we're working on hopefully creating easy-to-use guidelines for doctors, community doctors, so they can quickly lock it up and see. And as I said, we're waiting on FDA approval, wait on FDA guidelines and how they're going to look at the CPS story. JACOB KETTLE: Well, I think one of the most challenging things to grasp, especially with CPS, is that we're kind of used to biomarkers elsewhere in oncology, lung cancer, breast cancer, those kind of things where it's kind of a yes or no question. It's either present or it's not present. And that's radically different here when we talk about PD-L1 status, or CPS, or however you want to define it. Because it's the degrees of scale. And it seems to be different in all kinds of different malignancies. And I think that that really tends to be one of the harder pieces to grasp as we kind of really get immersed in this immunotherapy space. RONAN KELLY: Yeah, I would just comment on that. It's a real concern of a lot of people, I think. Because I think the academic doctors, obviously, who have a lot of time to follow the literature and involved in the studies, they'll be more well-versed in the different CPS cutoffs. But the community doctors who are so busy and treating multiple different tumor types, it's not going to be easy for them to keep up. So I think we're going to have to do a good job in helping them. And whether that's via pathway-directed treatments where the pathway may have to cut off so they can see that, I think that may be the easier way, rather than try to remember it all. It's going to be too complicated to remember. JACOB KETTLE: So with all that in mind, let's revisit that metastatic case. Where would you land for treatment with this patient? RONAN KELLY: Yeah. So as I said, it looks like this is a squamous cell esophageal. In the NCCN guidelines, we have the KEYNOTE 590 study, which was for esophageal cancer. And so that would be pembrolizumab. Again, we'll wait to see if there is an FDA guideline around what the CPS score may be. And if the question had been gastric or gastroesophageal junction adenocarcinoma, then I think CheckMate 649 would be the new standard of care, which is chemotherapy, so FOLFOX plus nivolumab. So just depends on whether it's an esophageal or whether it's a gastric GE junction, depending on which of those checkpoint inhibitors we'll see of people using. JACOB KETTLE: I think it's daunting, as complicated as these things are turning out to get. But I think from a patient perspective, it is really exciting to see when you venture out into these complexities, it means you're developing newer and better treatment options and more complex ways and more sophisticated ways of delivering care. So I really appreciate your insight on all those issues. I think, let's just close up by talking about where do we see things continuing to evolve, particularly in the area of immunotherapy, but maybe even in a broader sense, in esophageal and GE junction tumors moving forward? RONAN KELLY: There was a whole host of studies. Obviously, we won't go through them all in metastatic first line setting, second line setting. If we just take it in terms of the only study that's shown positive results in the adjuvant setting is CheckMate 577, I mentioned, there is another one we should see soon. But that's not with chemoradiation, it's with chemotherapy alone. So it's perioperative chemo plus pembrolizumab. That's KEYNOTE 585. So let's see. Let's see if there is a benefit using that approach. We cannot just assume that'll be positive. We've seen other studies negative in this space. So we'll have to wait and see what KEYNOTE 585 shows. If you look at some of the other studies in the US, ECOG-ACRIN have a study which is not too dissimilar from CheckMate 577, but they're giving nivolumab in the neoadjuvant setting when you're giving chemoradiation. And then, instead of doing nivolumab alone in the adjuvant setting after your operation, they're doing nivolumab plus or minus ipilimumab. So let's see if there's a benefit. Or, will there be more toxicities? Maybe patients won't be able to tolerate that. So we'll have to see. And then there's another one I'll just briefly mention. For those patients who are not eligible for surgery but, say, have locally advanced gastroesophageal junction cancer at GE junction who can't go for surgery, there is a definitive chemoradiation study with pembro, which is KEYNOTE 975. So there's a-- I know we have a whole host of other different IO-IL combinations emerging. We'll have to wait and see how those pan out in the future. JACOB KETTLE: Yeah, I don't think there's going to be any shortage of new content to stay familiar with, which again, exciting for patients. RONAN KELLY: But really, a tremendous year. If you look back, so just to summarize, if I could for the listeners, we've gone from really just relying on chemoradiation in early stage, stage II and III esophageal/gastroesophageal junction cancer, to now chemoradiation followed by surgery. And now, if you don't have a great response, you can get adjuvant nivolumab for a year. I think it's a major step forward. We showed a doubling in the disease-free survival from 11 months to 22.4 months. And we'll wait to see what the overall survival will show. Hopefully, that'll be available in the next year or so. But we have to just wait and see. And then, in the first line metastatic setting, I think CheckMate 649, KEYNOTE 590, very big breakthroughs this year. In the HER2 positive setting in the second line, we saw trastuzumab/deruxtecan emerge. So there's four major practice-changing studies that have just come in the last six to seven or eight months. Amazing, really, for our field. And we've got a lot more to come. We saw gastroesophageal, squamous cell have two approvals in the last year with nivo and pembro both approved. And then, as you very well pointed out, the TMB and the MSI status is also-- patients are eligible for checkpoints. So very major advances just in a very short period of time, I think. JACOB KETTLE: It's inspiring, frankly, to see all this innovation in a way that innovation that directly impacts patient care and quality of life and outcomes, and all that part of our mission. Again, it's inspiring. I truly thank you for your time today sharing your insights and expertise, and hope the same as for our listeners. Thank you all for joining. RONAN KELLY: Thank you for the invitation. Thank you very much. [MUSIC PLAYING]   ANNOUNCER: Thank you for listening to this week's episode of the ASCO e-learning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

How has Covid-19 has affected cancer care? Listen to the experts discuss postponing and modifying cancer treatment during a pandemic. Moderated by Dr. Helen Chew, featuring Drs. Mary-Beth Percival, Oliver Eng, and Toni Choueiri. We hope you enjoy this episode of the ASCO eLearning Podcast. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: elearning.asco.org | Contact Us (Airdate: 4/8/2021)   TRANSCRIPT [MUSIC PLAYING] SPEAKER 1: The purpose of this podcast is to educate and inform. This is not a substitute for 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.   DR. HELEN CHEW: Hello and welcome to ASCO's podcast episode focused on cancer therapy modifications during the COVID-19 pandemic. My name is Dr. Helen Chew, and I'm a medical oncologist and fellowship program director at the UC Davis Comprehensive Cancer Center. I am pleased to introduce our four guest speakers today.   Dr. Toni Choueiri is a medical oncologist specializing in genitourinary cancers from Dana-Farber Cancer Institute. Dr. Choueiri is also director of the Lank Center for Genitourinary Oncology and the Kidney Cancer Center and a Professor of Medicine at Harvard Medical School. We are also joined by Dr. Mary Elizabeth Percival from Seattle Cancer Care Alliance. Dr. Percival is a hematologist oncologist specializing in AML and myelodysplastic syndrome. She's also serving as an Assistant Professor of Medicine at the University of Washington and Fred Hutchinson Cancer Research Center. Our next guest speaker today is Dr. Oliver Eng, a surgical oncologist and Assistant Professor of Surgery at the University of Chicago. Dr. Eng focuses on treatment of cancers of the abdomen. And finally, we are also joined by Dr. Jennifer Sheng, a medical oncologist and Assistant Professor of Medicine at Johns Hopkins University. Dr. Sheng primarily treats patients with breast cancer.   Many oncologists around the world have been struggling with providing quality care during the pandemic. We are excited to launch a discussion of experiences at different institutions, guidance, and lessons learned that our listeners may apply in their own practice.   Starting with you, Dr. Choueiri, can you tell us about the International Survey of Oncologists you and your colleagues conducted in 2020 about the impact of the pandemic on decision making?   DR. TONI CHOUEIRI: Oh thank you, Dr. Chew. And I want to really thank ASCO for always being at the forefront here of educating the oncology community about the latest here, and we're all in this pandemic. And I remember where everything started, and we were just getting ready to see what we could do to protect our patient, our health care worker, with this novel coronavirus.   So one thing we've done as a group we started an online survey between March and April for a month. And that involved around 340 plus oncologists from 28 countries to understand what is the readiness measure taken by oncologists to protect patient and health care workers here? We really had no idea. We found first that the pandemic, really every country had an outbreak over 99%. PPEs were over 90% provided, and the telemedicine started early on. Around 80% of folks did telemedicine. We also saw that we did not have any routine testing for oncology patients. Only 3% performed systematic testing in all patients.   Then when we asked the oncologists, knowing we had no data, what do they think about systemic therapy? The vast majority thought that systemic therapy here you have to consider comorbidities and age. They also felt that hormonal treatment and tyrosine kinase inhibitors were relatively safe. On the other hand, cytotoxic chemotherapy and immune therapies potentially are not safe. Now we know for the future, when future studies done as part of CCC19 database and other, that there was no increase in mortality with immune checkpoint inhibitor, neither with cytotoxic chemotherapy in large part except perhaps if you consider the timing.   And finally one of the thing the survey showed that oncologists were still focused on neoadjuvant adjuvant first line metastatic disease, but they were kind of hesitant, more hesitant to recommend later line therapy in metastatic disease. So no doubt decision making by oncologists has been influenced by the ongoing COVID pandemic at that time. That was a year ago at the start.   DR. HELEN CHEW: That's really interesting. Did you find any of those results surprising?   DR. TONI CHOUEIRI: Well I would say, I would say no. But a lot of folks have their own biases overall. I do find that in a way that there are, for example, chemotherapy, and second, third line that extended survival and quality of life, folks seem to be hesitant. I didn't find it surprising we didn't have testing that folks-- patient didn't get testing much.   I was a bit surprised that telemedicine immediately made it, and it was around 80%. But that also included phone encounters. But this was overall a very large survey, and the median age of the oncologist were around early 40s.   DR. HELEN CHEW: Finally, can I ask you did you notice any regional differences since these were international survey?   DR. TONI CHOUEIRI: Yeah, absolutely. I mean in Europe there were from Italy and from France, at that time, things were obviously worse. There were some differences. That's a very good question depending where you are. And some of it folks did not experience, but they had the next door, if you want, experience more so than their own experience.   DR. HELEN CHEW: Thank you. Doctors Percival and Sheng, how has the COVID-19 pandemic impacted delivery of cancer therapy at your practice? What have been the major challenges in delivering quality patient care during the pandemic?   DR. MARY-BETH PERCIVAL: This is Mary-Beth Percival Yeah. So I would say that we didn't exactly conduct a survey, but instead my colleagues and I who care for patients hemalignancies at the University of Washington and the Fred Hutchinson Cancer Research Center got together and said, what evidence based guidelines can we come up with that may help to guide the care of patients, particularly those with hemalignancies?   As many of you are aware, the first patient in the US who was diagnosed with COVID-19 was from the Seattle area. So we kind of had a sneak peek into the pandemic before it officially became a pandemic. We've been relatively spared compared to some other areas, but certainly our patients with hemalignancies are at an increased risk of complications.   So I think that there were a number of changes that happened pretty quickly, and Dr. Choueiri spoke about some of these, like the increased use of telehealth when feasible was very rapidly taken on by both patients and providers. And we thought that that was a really important way to really reduce the number of touches that our patients had because they tend to require a lot of visits and a lot of care. And so if we can eliminate any of those we thought that that would be important.   We pretty quickly instituted screening for patients and providers on the entrance to the cancer center and were able to provide masks and rapid COVID testing, which is something that's still going on now and also really increased over time that asymptomatic COVID testing prior to procedures, and surgeries, and scheduled hospitalizations, prior to chemotherapy when possible, doing things like double testing when patients are admitted for a neutropenic fever in the setting of a hemalignancy because its sensitivity with the second test may improve for patients that are on, for example, the transplant service. They get weekly testing even when asymptomatic with the thought that they're at such high risk of complications given their immunosuppression that really knowing about that, and monitoring that, and also for the safety of patients and providers around them that it's important to do that.   I think another shift that really happened in our cancer center was trying to focus on outpatient regimens when that was possible. We weren't really sure what the hospital capacity constraints would be like when the coronavirus pandemic initially hit, and so making sure that that was going to be possible. And for a while we had really stringent transfusion thresholds for our patients who are transfusion dependent. So we lowered some of the hemoglobin and hematocrit goals to really be able to make sure that there was going to be enough supply given the decreased donor availability.   And then I think the final thing that was something that I think really pretty quickly impacted the delivery of cancer care at our site was to have, and I think this is important for oncologists all the time and so sometimes we need a reminder, but having early discussion about goals of care. And I think that it was pretty evident from some of the initial data that came out for patients from China and elsewhere where the pandemic first hit that patients with a history of malignancy or active malignancy, and this has been confirmed by subsequent retrospective studies, had really significantly worse outcomes when they were impacted by the virus. And so I think that that was really important for us to think about in talking to our patients about what they would want, especially when resources might be limited.   DR. JENNIFER SHENG: So similar to Dr. Percival, our group at Johns Hopkins decided to gather the entire group of breast medical oncologists as well as a few select surgical oncologists, radiation oncologists, and patient advocates to help us create guidelines for the management of breast cancer during the COVID-19 pandemic. And our hope from doing this was to create a stage and subtype specific approach to help guide others in their decision making process.   Ultimately, similar to Dr. Percival, I think it's important to remember that cancer care is very individualized, and so of course, we did factor in things such as age as well as comorbidities. And we did try to make visits less frequent when possible. And we ultimately relied pretty heavily on electronic means of communication, phone calls, video visits, and messaging through the electronic medical record. There are other changes that we made during this time. So for instance, we tried to minimize the use of steroids in order to reduce immunosuppression whenever possible, and as a result of doing that we more heavily relied on medications such as olanzapine or other antiemetic regimens. Additionally, we used prophylactic growth factors more frequently to reduce the risk of neutropenic fever.   We also tried to be mindful of patients and having to go to the pharmacy to pick up a lot of the medicines, and we would prescribe 90 day supplies instead of 30 day supplies. And we would try to anticipate this well in advance so that patients could opt for mail order or pharmacy delivery services during this time. For breast cancer specific patients that were on ovarian function suppression we were actually able to work with the insurance companies to allow a monthly self injection at home so they wouldn't have to come to the clinic every four weeks.   And additionally, we really thought about looking at people who are clinically stable and seeing if we could push out some of their imaging. So for instance, echocardiograms which may be done every, let's say three months, sometimes we'd stretch out to four months if they were clinically stable and didn't have any cardiac issues. Other imaging, such as a bone density scan, sometimes we would defer that depending on the situation. And similarly some of those antiresorptive or bone agents that we use in the adjuvant and metastatic setting sometimes we would try to see if we could defer that that timing.   And ultimately I think that we tried to just be really vigilant about how patients were feeling, and we would implement screening calls the day before their visit, inquire about any potential COVID-19 symptoms, and then we would actually screen them for COVID-19 symptoms again on the day of their visit. So overall I think we tried to implement as broadly as possible very safe measures for all of our patients and our staff.   DR. HELEN CHEW: Thank you and follow up to that, either Dr. Percival or Sheng, did you encounter any resistance to some of these changes that you made?   DR. MARY-BETH PERCIVAL: I can comment first. I actually think that there was not a lot of resistance. I think perhaps initially that was because of fear. A lot of patients were really nervous about congregating in any kind of public space even if they realized that we're always weighing the risks and benefits, and that we felt that if we were asking them to come in that the benefit of being seen in person was actually going to be there.   But I think it also speaks to the fact that now later, when sometimes patients don't want to come in when we do think it's actually a lot safer and there hasn't been a lot of transmission in outpatient hospital or clinic settings, I think that now patients are getting very used to telehealth. And in a lot of ways I think that's great, but it's going to be interesting to see what the ramifications are from insurance reimbursement when some of the emergency policies that have been put in place by first the Trump administration, now the Biden administration expire.   So I don't know. It's going to be a hard roll back if we are not able to offer telehealth to the same degree to our patients, especially when I'm for example, at an academic medical center with a really large catchment area. Two weeks ago I was on the phone or telehealth with somebody who is in Fairbanks, Alaska, 1,500 miles away so.   DR. JENNIFER SHENG: Certainly, I agree with that sentiment that we had a wide range of responses. And I think when it was ever with regards to perhaps delaying imaging or delaying treatment there was a lot of anxiety, but if it was, for instance, let's convert to a video visit, I think that probably three quarters of my patients are really enthusiastic about not having to drive to clinics, being able to do this call with me while sitting on their sofa, being able to be next to their significant other or family member was really important because unfortunately in our clinic, even now, we actually don't really allow any visitors with the patient. And I think having that family member or friend, there is so critical. So I think that there was mixed responses overall.   DR. HELEN CHEW: And follow up to that, Doctors Eng and Percival, can you discuss the adjustments to care you have made in response to the COVID-19 pandemic? What major factors played to your decision to modify care?   DR. OLIVER ENG: Sure. So thanks again to ASCO for the invitation to participate in this panel. And so I think from a surgical perspective, it definitely offers some different challenges that are complementary to the challenges that we've discussed already. And so I think when the pandemic arrived and we were just going through the initial stages, there was a lot of uncertainty with the impact of the pandemic itself and surgical patients. And certainly the earlier literature that came out demonstrated high morbidity in patients with cancer who underwent surgery. And so it sort of generated a lot of sort of downstream thoughts about how do we approach surgical cancer care during this pandemic, and how do we navigate this?   And I would say initially, when COVID first arrived, we essentially stopped surgeries, elective surgeries, for some time. And I think that was what was done at many centers as well because we just did not know the consequence of these things. And so a lot of what I wrote about initially when this was happening was that typically surgeries are thought of as being dichotomized between elective and emergent or urgent procedures, but as you know, cancer care falls somewhere in between in most instances. And so I think it's a little bit simplistic to think about it in this dichotomous way.   And so one of the aspects that we talk about was cancer timing and sort of prioritizing surgical cancer cases during this time of not only just postponement but backlog of cases once cases were resumed. And so I think this is kind of a joke, but a lot of us who do surgery were sort of sidelined during this period so then we all just started writing at University of Chicago. And so a lot of us were putting out papers regarding this. And so one of my colleagues, Dr. Kiran Turaga, put out a paper which discussed what was called a safe postponement period of surgery which looked at the fact that the typical time period between when systemic therapy was received, and in what surgery was performed, and is there safe window after that or sort of within that several weeks where we can actually perform surgery and not have a inferior outcome? Again this is just retrospective, it gives us some idea of how to prioritize surgery and that paradigm.   But also it's a complex decision making process, not just the surgery itself, but the institutional resources required for hospitalizations after surgery, the staff that are involved. And not only just staff but trainees as well, and making sure they're compliant with [INAUDIBLE] making sure they're safe, first and foremost, during this whole process. And then working COVID testing into this whole algorithm itself was challenging, to say the least.   DR. HELEN CHEW: Thank you. Dr. Percival, do you want to add anything in addition?   DR. MARY-BETH PERCIVAL: Sure. I think that it's interesting to hear about things from the surgical perspective. It's not something that plays into the care of my patients with hemalignancies, particularly AML, as much as for other specialties, but it's certainly interesting to hear about that. So I think AML is typically a disease that we approach with curative intent, and induction chemotherapy, which is kind of the mainstay of initial treatment, is generally started on an urgent, sometimes emergent, but more of an urgent basis. And so I think we and colleagues were really trying to figure out what would be supported by the literature when we put together recommendations that were published in the Journal of Oncology Practice.   So we have done some trials at our institution, one for what we call early hospital discharge. So instead of keeping patients in the hospital for an entire month, we usually discharge them after receipt of induction chemotherapy to get close outpatient follow up. And so we suggested that that might be something if other centers were equipped to be able to provide the necessary supportive care as an outpatient to consider to decrease hospital utilization, especially in the setting of hospitals being overwhelmed by COVID patients.   We also had a pilot study that was done also out of our center for outpatient induction chemotherapy. So maybe patients could be completely outpatient to receive their chemotherapy, which is not generally how we think about things for AML patients. But there is some supporting literature to suggest that that might be possible. So for example, moving to diffuse large B cell lymphoma, for example, there are some regimens where older patients receive abbreviated chemotherapy and consolidated radiation therapy. So looking at things like that that are reasonable alternatives with evidence behind them was really kind of what we wanted to do to disseminate recommendations and try to be as specific as possible.   I would say one thing that I think is probably going to be talked about on another ASCO podcast but that has come up a lot at our academic medical center is clinical trial enrollment. And so similar to surgeries being cut off completely for a while, clinical trial enrollment was slowed almost to a halt because basically all phase I and phase III trials were closed. Phase II trials were felt, in a lot of cases it was taken on a trial by trial basis, but felt to offer opportunities for patients that they wouldn't be able to achieve in other ways. And I think that there are going to be a lot of long term downstream effects from that clinical trial enrollment stuff that we are yet to see, and I think particularly for patients with relapsed/refractory disease and that kind of thing, that's going to be something that really comes up in the future. And I think also in terms of things like referrals to our center that some of that may decrease as well if we are not able to offer clinical trials to the same extent in the future.   So I think there are just a lot of things that come up when we're caring for patients and modifying therapy for patients. And I think there's going to be a lot that will come out in the future, even though we're moving more towards whatever our new normal is going to be like and having more access to trials and other more standard procedures these days.   DR. HELEN CHEW: Thank you both. Doctors Eng and Sheng, what guidelines or protocols have you relied on to make decisions on therapy adjustments since the start of the pandemic?   DR. OLIVER ENG: Great. Thanks for that question. So in the realm of surgery, we actually, my colleagues at the University of Chicago actually, put out a paper which we, again, like I mentioned, the dichotomization of elective versus non-elective procedures was a bit simplistic. And so we actually devised a scoring system here at University of Chicago. We termed it medically necessary time-sensitive procedures. And so it took into account the procedure itself, the disease, and patient factors. And we were all required to submit a score for each patient we were proposing to do surgery on during this period. And basically, procedures were selected in conjunction with the actual score the patient was assigned, because it was felt to be attributable to appropriate risk within the context of the pandemic.   And so at least at an institutional level, we utilize this not only during the first wave but the second wave as well, and it seemed to be able to triage patients appropriately based on all these aspects. But of course, like we have discussed, cancer care is individualized. And so it is still difficult to try and put a number to a patient, for sure. But we did certainly consider each patient individually with all aspects of their care.   I think from a regional perspective, in the state of Illinois we've come together and formed the Illinois Cancer Collaborative which has developed COVID-19 guidelines as well throughout the state which has been a nice collaboration amongst a lot of the hospitals and distributed amongst the communities. And certainly societal, national recommendations have been put forth as well. The Society of Surgical Oncology has put forth guidelines for multiple disease sites, and so that's been the consensus recommendation from leaders of our society.   I think just to give a little perspective, my specialty is primarily in peritoneal malignancies and metastatic malignancies, and so certainly patients who are undergoing cytoreductive surgery for a low grade disease, for example, was postponed for some time. And patients with higher grade disease were kept on systemic therapy for longer, and then certainly when they're within that window for operations, sort of recommendations for delaying operation dependent on the aggressiveness disease were adjusted accordingly. And so that's just one aspect of all the recommendations that were put forth.   DR. HELEN CHEW: Dr. Sheng?   DR. JENNIFER SHENG: Yeah. So I think we heavily relied on seeing what our peers nationally and internationally did during these times. The COVID-19 Pandemic Breast Cancer Consortium did release guidelines and recommendations. So we certainly relied on those because they provided a tiered approach to prioritizing surgery, radiation, and systemic therapy interventions by urgency, and within those guidelines there was certainly discussion about weighing the risks and benefits of delivering immunosuppressive therapy, about a delay of non urgent surgeries, the use of neoadjuvant systemic therapy due to deferral of many breast surgeries during the initial pandemic, and also discussion of the genomic tumor profiling on core biopsy specimens to guide neoadjuvant therapy decisions.   And so from there, our group thought that it would be prudent to just really gather together and really create more focused guidelines with a few more specifics about how to care for early stage breast cancer, metastatic breast cancer, and I think I briefly highlighted, some of the changes that really applied to many of our patients regardless of their stage. And then I think more specifically for patients who had metastatic breast cancer, for instance, we would try to consider oral regimen as opposed to IV regimens, and really tailoring that to patients and also trying to decrease the total number of visits to the cancer center. We would also defer some of the re-staging scans and lengthen the intervals between scans of patients who are clinically stable. We were able to extend the interval between port flushes for patients to 12 or of longer.   And we really tried to be really cautious when we looked up the side effect profile of a lot of the agents that we use. So for instance, really trying to balance the risk of pneumonitis for the use of immunotherapy, the risk of interstitial lung disease with certain types of [INAUDIBLE] II therapy that have been approved, and really thinking about some of the oral agents that we provide for metastatic hormone receptor positive breast cancer that require some more frequent blood work and labs and seeing what if we could delay that if we were able to implement initial endocrine therapy. So overall I think that everyone was trying to think of ways to keep our patients as safe as possible. And there were quite a few institutions and organizations that gathered, like minded individuals to be able to come up with these guidances.   DR. HELEN CHEW: Thank you both. Dr. Choueiri, in the upcoming months as the vaccination rolls out, do you think you will start reverting to pre-pandemic patient management at your institution?   DR. TONI CHOUEIRI: Oh, thank you for your question. Actually, I mean the short answer is I don't know. I think it's hard to say who is in control. I know who is in control. The virus is in control. Yes, there are a lot of signs, positive signs, happening, but we don't know what later on things going to happen. I personally think that stuff won't go back to normal immediately.   First, we can't expect everyone, all our patients, to be vaccinated despite our recommendation. Second, I would think that some folks are comfortable doing what they learned and they still want to have a mixed telemedicine. I'm talking not just physician but patient. They want a mix of telemedicine, face to face, and we have to see what's the implication of that is. There are some implications, of course, for out-of-state consult if patients have licenses there. There are indication on billing perhaps, although some preliminary data shows that this is going well.   What I want to say is some silver lining, hopefully, that our clinical operation and our clinical trials operation could be a bit more efficient after we learned how to be overall more efficient. We recently wrote with Doctor [INAUDIBLE], a German oncology, a piece about that. I think there will be a transition. The good thing is that there are processes, safety processes, best practices now that we know very well that we didn't know at the beginning of the pandemic, and that actually is reflected by a study we did in the Mass General Brigham Health Care System where we looked at the screening for cancer and compared the three months between March and June index case, the three months where we had the first pandemic, if you will, in the first peak, compared to three months prior, three months after, and three months into 2019. We saw, because of cancellation of a lot of elective procedure, we saw 80% decrease in screening.   But that picked up. It didn't pick up completely, but it did pick up because we have safety measures in place. So I think it will be a gradual increase, and we just have to learn as we go.   DR. HELEN CHEW: Thank you. Yes, it's certainly been a learning process. And I think some of the changes we've made are probably here to stay.   DR. OLIVER ENG: Yeah, I think the one thing that should not be forgotten is the impact on patients and their perception of delays, and it's very easy to think of this from an academic perspective of OK, it's safe to delay because of disease biology, and so and so and, make decisions based on the duration of therapy and so forth. But to call a patient, which all of us have had to do, to delay the therapy for a variety of reasons and explain why. I think it's something that we need to be cognizant of when we are making these decisions and really being transparent with the patients about the fact that we're taking consideration not only their risk but the risk to the community as well. And it's just made things a lot more complex. And time will tell as to the sort of sequelae of everything, all the decisions that are made in this period.   DR. TONI CHOUEIRI: I like that Oliver. I think that's very sensible honestly. I think there's wording. Sometimes it's not from us, it's the patient who want to delay. But I think the word delay does have some negative connotations, and actually, funny enough, when we did our paper in Journal of Oncology about screening, which went down, then up, and compared this, a reporter asked me directly, he said look, these patients were delayed. Did you missed the diagnosis?   And you can't-- it's just a bit, so the word we used is kind of postponed. I think despite it is a bit the same, but I think it looks-- because delay is negative. Delay implicates that we're missing something while it's mostly postponing some things that normally maybe you would this is not BEP for testicular cancer that you would anyhow want to delay, but this is postponed. So this was very sensible, and I agree with you.   DR. HELEN CHEW: Thank you. So that is all we have time for today. Thank you all for your time to share your valuable perspectives. For listeners that want more, look out for upcoming episodes in ASCO's eLearning series on COVID-19's continually evolving impact on cancer care.   [MUSIC PLAYING]   SPEAKER 1: Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

In this episode of the ASCO eLearning Podcast, Gregory Masters, MD, and Christina Dieli-Conwright, PhD, MpH, dive into the exciting benefits of exercise for patients with early-stage cancer, advanced disease, and how exercise could preemptively lower risk. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org.   TRANSCRIPT CLIFFORD HUDIS: Hello, I'm Dr. Clifford Hudis, CEO of ASCO, dropping into your feed to let you know about a special episode of the ASCO in Action podcast featuring the extraordinary career of Dr. Richard Schilsky, ASCO's chief medical officer. Rich and I discuss the advances that have revolutionized cancer care over the last 50 years and much, much more. Here's a preview of the episode. RICHARD SCHILSKY: The 1980s, in many respects, were the doldrums of progress in clinical oncology. There really was not a lot of innovation in the clinic. But what was happening and what was invisible to many of us, of course, was that was the decade of discovery of the fundamental biology of cancer. That's when oncogenes were discovered, when tumor suppressor genes were discovered, when it became clear that cancer was really a genetic disease. And that is what transformed the field and put us on the path to targeted therapy and precision medicine as we think of it today. CLIFFORD HUDIS: You can find the ASCO in Action podcast on Apple Podcasts or wherever you are listening to this show. And you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org. SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for 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. GREGORY MASTERS: Hello, I'm Dr. Gregory Masters. I'm a medical oncologist at the Helen F Graham Cancer Center in Delaware. CHRISTINA DIELI-CONWRIGHT: And my name is Christina Dieli-Conwright. And I'm a member of the faculty at the Dana-Farber Cancer Institute in the division of population sciences and department of medical oncology. GREGORY MASTERS: We would like to discuss the role that exercise and physical activity can play in providing excellent cancer care to your patients. And we'll start with a brief case presentation to review how exercise can improve the care in patients with early-stage cancer. The first patient is a 51-year-old postmenopausal female who presented with stage IB hormone receptor positive, HER2 negative breast cancer. Sentinel lymph node biopsy was negative. And she underwent lumpectomy, followed by radiation therapy. She had a low recurrence score on the 21-gene expression assay and saw a medical oncologist to consider additional therapy. She agreed to take anastrozole off for five years. At the end of the office visit, she poses the question, besides surgery, radiation, and hormonal therapy, what else can I do to improve my chances? CHRISTINA DIELI-CONWRIGHT: What is the role for exercise in patients with early-stage cancer? GREGORY MASTERS: Well, Christina, it's important to understand that exercise can help improve and maintain a healthy lifestyle in most patients, regardless of a cancer diagnosis. But there's a particular benefit in cancer patients and, also, in helping to reduce the risk of cancer as well. Studies show a decreased risk of getting certain cancer in patients who exercise on a regular basis. There's a decreased risk of developing cancer of the breast, colon, endometrium, kidney, bladder, esophagus, and stomach. The hazard ratio is 0.6 to 0.9 for developing these cancers. That is, there's a 10% to 40% reduction in the risk of getting one of these cancers. The evidence is convincing, with both statistically and clinically significant reductions in developing cancer. There's also evidence that sitting time or complete inactivity may increase the risk of cancer. Multiple types of exercise can help, including both recreational or leisure time exercise and occupational physical activity. Those who are very active at work may achieve a similar benefit. CHRISTINA DIELI-CONWRIGHT: How does this affect quality of life and cancer outcomes? GREGORY MASTERS: So exercise can help reduce the risk of developing cancer. But exercise also improves health in patients who are being treated or have been treated for early-stage cancer. Physical activity has been correlated with improved cancer-specific and all-cause mortality. That means physically active patients are less likely to die of their cancer or other causes. A hazard ratio for death is 0.67 to 0.7 for breast, cancer, and colorectal cancer patients. That means there's a 30% reduction in the risk of death in those who exercise regularly. This holds for both prediagnosis exercise and postdiagnosis exercise. So patients who are already in an exercise routine when diagnosed and those who begin an exercise program after their cancer diagnosis can achieve benefits from exercise. There appears to be a dose-response relationship. So the more one exercises, the better, within reasonable guidelines. The American Cancer Society estimates that about 15 million cancer survivors alive in the United States may benefit from exercise. But there are some limitations to these studies. There may be patient recall bias, meaning that some patients may overestimate their activity to please questioners. These data also come from nonrandomized studies for the most part. So other factors, such as a healthy lifestyle, may also be at play. Some studies compare the highest to the lowest risk groups to calculate the risk ratio. So the data may overestimate risk reduction in some patient groups. Another benefit is that symptoms can improve with exercise, leading to a better overall quality of life. Studies have shown an improvement in fatigue, physical functioning, and physical fitness, and a reduction in depression and anxiety. And of course, the added benefit comes that overall cardiovascular risk may be reduced with exercise. CHRISTINA DIELI-CONWRIGHT: Is it safe to exercise during chemotherapy and/or radiation therapy? GREGORY MASTERS: Exercise is safe in the cancer population. In studies looking at adverse events in patients enrolling in a postdiagnosis physical activity program do not show unexpected safety concerns. Nonetheless, there remain major challenges in implementing these recommendations in the broad cancer patient population. One problem can be getting providers to adopt the recommendations. Another issue is time constraints for both patients and health care providers. There may be knowledge deficits in providers. And although 79% of oncologists agree that referral to an exercise program is important, in one ASCO survey, only 10% to 20% of providers actively refer patients to these programs. One strategy for getting providers and their patients engaged may be to assess, advise, and refer. This is one way to support providers in the steps needed to boost participation. There can also be constraints from a patient-care side. Getting patients to follow through on our recommendations can be a challenge. And we need to focus on behavioral changes. Patients need a strong support system, including not only their oncologist, but also family and caregivers, oncology, nurses, physical therapists, occupational therapists, and trainers to help them with their routines. Specific programs can be helpful, such as Livestrong at the YMCA. A patient's access to this care can be limited for various reasons, socioeconomic or otherwise. But we know that cost, insurance coverage, and time out of work can be a challenge. It may be difficult for these patients to commit more time and effort to an exercise routine after going through extensive treatment. And we know there's a dire need to reach underserved populations. This is a perfect time to remember the focus of Dr. Lori Pierce, the current ASCO president, who has as her theme, equity, every patient, every day, everywhere. Remember, we can all work together to help our patients strive for their best health through exercise. And for our early-stage breast cancer patient, to help her improve her chances, in addition to standard care, I would recommend a regular exercise routine, perhaps with referral to a specialist in exercise physiology. CHRISTINA DIELI-CONWRIGHT: Greg, are there specific clinical concerns to address? GREGORY MASTERS: As a medical oncologist, before I refer a patient for exercise, I consider comorbid medical conditions, such as cardiac, pulmonary, orthopedic, central nervous system, and neurologic complaints, and any post-operative limitations that may be appropriate. Thank you. CHRISTINA DIELI-CONWRIGHT: I have the pleasure of discussing a second case with you today. And this case is a 60-year-old male who underwent surgery five years ago for stage II colon cancer. Earlier this year, his CA tumor marker was elevated. And a CT scan showed new metastatic disease in the liver and lung. Biopsy confirmed metastatic adenocarcinoma. Molecular testing shows the cancer is KRAS mutation positive. Symptoms include fatigue, anorexia, and mild cough. And he still gets occasional diarrhea since surgery. He begins chemotherapy with FOLFOX and bevacizumab. At the next visit, he has increased complaints about his energy level and mild depression. He asks, besides chemotherapy, what more can I do to improve my quality of life? So I'm here to share with you today the role of exercise and its benefits in a case just like this, with patients with metastatic cancer. GREGORY MASTERS: What is the role for exercise in patients with advanced cancers? And how does it affect their quality of life, symptom management, and prognosis? CHRISTINA DIELI-CONWRIGHT: So this is a very interesting question, given that very few studies, intervention studies specifically with exercise, that have actually targeted specifically patients with metastatic disease. However, there are pilot studies that have smaller patients enrolled that have shown that exercise is feasible and safe for patients with metastatic disease. And to date, exercise in patients with metastatic disease, although few, have shown to improve quality of life and physical function. And by physical function, I'm referring to how quickly an individual is actually able to walk and the distance by which they're able to walk over a certain period of time. So importantly, we need to emphasize that research is actually heavily lacking in this population. So further and ongoing research that has yet to be published is underway and needed to determine whether exercise can impact symptom management and also improve prognosis in patients with metastatic disease. GREGORY MASTERS: What safety precautions should a patient be aware of when performing exercise? CHRISTINA DIELI-CONWRIGHT: So it is advised to have an understanding of one's own physical personal strengths and weaknesses as well as prior medical history before initiating exercise. And perhaps this is even more important in an individual with a metastatic diagnosis. Importantly, consideration of daily aches and pains, overall well-being, time since last exercise was performed regularly are important, but just a few examples of considerations to understand. This basic information will really help to determine which forms of exercise are safe and which forms of exercise should be future recommended. Consulting with a medical oncologist prior to starting an exercise program is advised. And subsequently, that physician may also refer that patient to see a professional exercise specialist. In line with this recommendation, there actually are specialized exercise professionals with unique training in exercise for cancer patients, who can assist in providing personalized exercise guidance for patients with cancer. And it is possible to seek out those recommendations using a website provided by the American College of Sports Medicine. GREGORY MASTERS: Will exercise during treatment aid in how well a patient tolerates treatment? CHRISTINA DIELI-CONWRIGHT: Exercise during treatment may aid in how well a patient tolerates treatment. However, there is no scientific evidence yet to support this, specifically within the metastatic population. Logically, we do know that exercise during treatment has many physical health benefits, such as maintaining strength and physical endurance. And that may help to keep the patient fit so that they're able to better withstand the treatment as opposed to if they were not fit. However, studies are underway to help to continue to support this logic. GREGORY MASTERS: What are the best ways to help patients understand this information and to get them to initiate and stick with an exercise routine? CHRISTINA DIELI-CONWRIGHT: So this is a fantastic question and this is a question that highlights the challenges of individuals difficulties adhering to regular exercise, in general, throughout the lifetime. However, there are some great resources specific to individuals diagnosed with cancer that are worth mentioning. For example, website and organization referred to as cancer.net offers a number of brief articles focused on exercise that provide great readings around the benefits of exercise before, during, and after treatment, et cetera. Often the easiest way to get started and to stick with exercise is to start with an enjoyable activity that will be based on one's personal preference and to start small. It's not necessary to choose an activity that is completely unenjoyable or for an excess amount of time because then that will often result in a person not adhering to what they're trying to achieve. Exercise can often appear very daunting when it's examined in a very high volume or at a very high intensity if that's the only way that it's thought to be able to be performed. So starting simple by taking short walking breaks to reduce sitting time can actually go a long way. And there's more and more research to support the benefits of reducing sitting behavior. Individuals are also more likely to stick with an activity when they enjoy the activity and when it is not too time consuming. Another tidbit is exercising with family, friends, or in a group setting when it's safe can also promote consistency with exercise. Nowadays, there are a lot of virtual exercise programs in light of the COVID pandemic that actually can involve exercising in a group with family or with friends but being socially distant via virtual platform. Also important to note, when approaching more advanced forms of exercise, such as weightlifting or training for a specific event, such as a running event like a half marathon or a 3K, 5K, it is definitely helpful to seek professional assistance, even if for a single consultation. This way you're on a straight and clear path of how to safely go about performing the exercise. And specifically, with our patient diagnosed with metastatic disease, exercise is safe and feasible. However, relying on consultations by medical oncologists and also exercise professionals will really help to put that individual in safe hands to get off on a safe start in order to perform the exercise and help to benefit the improvements of quality of life and strength and physical function that we know are well-established among cancer survivors. Thank you so much for your time. GREGORY MASTERS: Now that we have reviewed these two cases, let's consider how these cases are related. There's evidence that exercise benefits patients with both early-stage cancer and advanced disease. There's also evidence that exercise can help reduce the risk of cancer prior to diagnosis. Based on these studies, there's strong evidence supporting our recommendations to patients that they become more active. Beyond understanding the data, sometimes the hardest component of this is getting patients to implement our recommendations. The take-home point should be that exercise helps both groups of patients and that we should be recommending exercise for this patient population. CHRISTINA DIELI-CONWRIGHT: The key teaching points from our session today should be recommending exercise for patients with early-stage or advanced cancer is evidence-based and will improve multiple health outcomes. The goals, therefore, are coming up with the best way to teach our patients this information and helping them to act on that knowledge. Barriers may include lack of energy, which limits patients initial interest to pursue exercise as therapy. GREGORY MASTERS: Thank you for listening to this week's episode of the ASCO eLearning Podcast. SPEAKER: To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

Dr. Stephen Hunger is a Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. In today's ASCO eLearning Podcast, Dr. Hunger will discuss two patient cases related to CAR T-cell therapy. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts or Google Play. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org.   Transcription:  The purpose of this podcast is to educate and inform. This is not a substitute for 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. Hi, my name is Stephen Hunger. I'm a professor of pediatrics in the Perelman School of Medicine at the University of Pennsylvania, and chief of the Division of Oncology and director of the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia. My career has focused on clinical, translational, and basic research regarding childhood Acute Lymphoblastic Leukemia, or ALL. One of the most exciting recent advances in cancer medicine is the development of Chimeric Antigen Receptor-redirected, or CAR-T cell therapy for relapsed in refractory pediatric B cell ALL. Today, I will present two cases that have similarities, but also important differences that highlight key questions and uncertainties regarding when and how to use CAR T cells in pediatric ALL. Currently the only CAR T cell product FDA approved for treatment of children and young adults up to age 25 with relapsed refractory ALL is tisagenlecleucel, trade name Kymriah. Additional CAR T cell products are in the late stages of testing, and will likely become FDA approved soon. My discussion today will focus on tisagenlecleucel, which can persist for years following therapy. Indeed, the first child treated at CHOP for ALL with CAR T cells in 2012 still has detectable CAR T cells over eight years later. Our first patient is Sue, who is currently 15 years old and has B-ALL that relapsed for the second time. She was first diagnosed at age 7, at which time she had an 80,000 white blood cell count. She was treated with standard chemotherapy with an excellent response, but relapsed during maintenance therapy 22 months following her diagnosis. Because this relapse occurred on therapy, she was considered high risk, and allogeneic transplant was considered the therapy of choice. She entered a second remission and became MRD negative after two cycles of consolidation therapy. Her brother was HLA identical, and she underwent a matched sibling transplant in MRD negative second remission following a cyclophosphamide mind plus total body radiation preparative regimen. She engrafted rapidly, had no GBHD, and was weaned off immunosuppression by six months post-transplant. One year post-transplant, she presented with bone pain and was found to have a second bone marrow relapse of B-ALL. Her leukemia cells were CD19 positive. Our second patient is 15-year-old Damian, who was diagnosed with CD19 positive B cell ALL four months ago. His initial white blood cell count was 80,000, and the cytogenetic and molecular studies did not show any known high or low-risk features or targetable lesions. He was treated with standard chemotherapy, but did not enter remission with 50% blasts at the end of four weeks of induction therapy. He received one month of consolidation chemotherapy with a Children's Oncology Group augmented BFM regimen, but still had 35% blasts after that therapy. He then received a four-week course of the CD3/CD19 BiTE blinatumomab, but again had 30% blasts at the end of that therapy. The blasts remained strongly CD19 positive. His 17-year-old sister is fully HLA matched. Both of these patients have relapsed refractory ALL, and meet the FDA approved indication for tisagenlecleucel, which is patients up to 25 years of age with B cell precursor ALL that is refractory or in second or later relapse. Sue is in her second relapse, and thus qualifies. Refractory is not defined precisely in the indication, but I think all would classify Damian as having refractory ALL, given that he has failed to enter remission with three different regimens. The pivotal trial that led to the approval of tisagenlecleucel was called ELIANA, and the results were published in the New England Journal of Medicine in 2018, with my colleague Shannon Maude being the first author. Of note, that study prohibited patients who had received prior CD19-directed therapy, so Damian would not have been eligible to enroll. However, the FDA label does not mention this, and many patients have been treated with tisagenlecleucel following earlier blinatumomab therapy. Thus, Sue and Damian are good candidates for tisagenlecleucel. Both are also medically in good condition without active infection or end organ dysfunction. There are also important differences between Sue and Damien. Sue has relapsed post-transplant while Damien has an HLA-matched sibling, but has never undergone transplant because he has never entered remission. Transplant with high level marrow disease, as he has currently, 30% blasts, is generally viewed futile, and the best transplant outcomes occur when patients are MRD negative immediately pre-transplant. A key current question in therapy of relapsed refractory ALL is whether CAR T cells should be used as a definitive therapy with responders receiving no subsequent antileukemia treatment, or as a so-called bridge to transplant, a means to get patients to an MRD negative state so that they can then undergo transplant as definitive therapy. There is no current definitive answer to this question, and these two cases help to highlight the issues to consider. Both Sue and Damian undergo T cell apheresis with a good collection. Cells are sent to the manufacturer to make the CAR T cells, a process that takes about four weeks. They receive low-intensity maintenance therapy for two weeks with adequate disease control, and then no therapy is given for two weeks. Both have adequate manufacture of CAR T cells, and then receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by CAR T cell infusion. Both patients have mild signs of cytokine release syndrome not requiring intervention. At day 30 post-infusion, both Sue and Damian are in an MRD negative complete remission and have no detectable circulating B cells. What should happen next? While some feel that the long-term efficacy of CAR T cells have not yet been established, and that transplant should be used as a consolidative therapy in almost all cases, many others believe that a long-lasting CAR T cell product such as tisagenlecleucel can be used as definitive therapy in some cases. In the initial ELIANA publication, 81% of the 75 relapsed refractory ALL patients infused with tisagenlecleucel obtained in MRD negative complete remission within three months, usually after one month. And the 12-month event-free survival and overall survival rates were 50% and 76%. More mature survival data from ELIANA shows a two-year relapse-free survival rate of 61% among those achieving remission. Like Sue and Damian, the patients in this trial were heavily pretreated with a median of three prior regimens and 61% had previously undergone transplant. Knowing that many patients can survive long term with no further therapy post-CAR T cell infusion, there is limited enthusiasm for a second transplant among physicians, patients, or their parents if a good response is obtained and maintained. So for Sue, I would recommend close monitoring, but no additional therapy as long as she showed continued evidence of response for 6 to 12 months. I would repeat bone marrow MRD testing at 60 and 90 days and every three months thereafter, and measure peripheral blood B cell numbers monthly for at least six months. B cell depletion is a good surrogate for CAR T cell activity, as normal CD19 positive cells are also killed. If Sue remains MRD negative and has no circulating CD19 positive B cells for at least six months, then there is a good hope that no more therapy is needed. Damian is a more complicated case, as he has never undergone transplant and has an HLA-identical donor, and now has excellent disease control and is in good medical condition to undergo a transplant. There are short-term risks of transplant with a 100-day mortality risk of 5% to 10% for a teenager. And there are also long-term risks related to the transplant procedure and/or graft versus host disease. The long-term risks of tisagenlecleucel appear limited other than the persistent B cell depletion, but the longest followup is only eight years, and few patients have more than five years of followup. So we have no idea about the efficacy and potential risks 10 to 20 or more years post-infusion. Damian failed three induction attempts. If his leukemia comes back, one may never be able to get him back into a healthy MRD negative remission. So there is a good argument that his best chance for definitive therapy is with transplant. Given this, many would strongly recommend transplant as consolidative chemotherapy for Damian. However, it's also possible that Damian has now received curative therapy and will never relapse. Highlighting the uncertainty surrounding this question, our group at CHOP, which has treated over 300 patients with relapsed refractory ALL with CAR T cells, does not have a clear consensus on what to do for patients like Damian. It's our practice to summarize the potential advantages and disadvantages of transplant versus no further therapy, and help the patient and their family decide what is the best course for them. To summarize, tisagenlecleucel is an exciting therapy that provides new opportunities for children and young adults with relapsed and refractory ALL. However, the field of cellular immunotherapy is young, and there are many uncertainties, particularly surrounding the issue of definitive therapy versus bridge to transplant. Today, we lack the followup data needed to make definitive statements, and patients and families need to understand that and be full partners in these complicated decisions. Thank you very much for listening. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

Dr. Raja Mudad is a medical oncologist specializing in lung cancer at Florida Precision Oncology. In today's ASCO eLearning Podcast, Dr. Mudad will discuss two patient cases related to the treatment of advanced non-small cell lung cancer harboring an EGFR mutation. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts [https://podcasts.apple.com/us/podcast/asco-elearning-weekly-podcasts/id1375021523] or Google Play [https://play.google.com/music/listen?u=0#/ps/Igjyhvqqrvuc5mjvlljhzkpvgeu]. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org [https://elearning.asco.org/homepage]. The purpose of this podcast is to educate and inform. This is not a substitute for 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. Hello. My name is Raja Mudad. I'm a medical oncologist specializing in lung cancer. I work at Florida Precision Oncology, a practice dedicated to an academic approach in the treatment of cancer. Today, we compare two patient cases that relate to the treatment of advanced stage non-small cell lung cancer harboring an EGFR mutation. These two cases have similarities, yet the recommended treatments may be different. Let us look at the cases. Patient case 1, our first patient case is Roberto. He is a 34-year-old man with stage 4 non-small cell lung cancer harboring an EGFR deletion 19 mutation. The patient, a never smoker, presented with chest pain and was diagnosed with a pulmonary embolus. CT scan of the chest also demonstrated bilateral lung nodules. Biopsy revealed adenocarcinoma. Staging workup revealed multiple small brain metastases. Patient case 2, our second patient case is Heidi. She is a 60-year-old woman with stage four non-small cell lung cancer with an exon 21 mutation in EGFR gene. She presented with a cough. A CT scan of the chest showed a left lung mass. An endobronchial ultrasound guided biopsy revealed no evidence of mediastinal disease. And a biopsy was positive only in the mass showing adenocarcinoma. She was taken to surgery but found to have multiple pericardial nodules. No distant metastases were seen on the PET scan. The two cases are clinically similar. Would any of the differences lead you to select a different treatment for each patient? Let's take a look. The two patients have the exact disease, a similar stage, and mutations in the same EGFR gene. Their initial treatment is the same. The initial treatment in both cases, osimertinib, is considered the standard of care in the United States, with a median progression-free survival of 19 months. Roberto started on treatment with osimertinib, and the follow-up PET scan and brain MRI showed complete resolution of all of the abnormalities. In the second case, surgery was aborted, and the patient started on osimertinib. About 1.5 years after Roberto started on osimertinib, progressive disease developed with a new adrenal mass, a new bone metastasis, and progression in the brain. He received stereotactic radiosurgery to the brain. A repeat biopsy of the adrenal mass revealed the same histology but with a MET amplification detected on next-generation sequencing. About eight months after starting osimertinib, Heidi developed progressive disease, and a repeat biopsy confirmed the same histology and the original EGFR mutation but no additional abnormalities. As you can see, the two cases are similar at presentation. However, upon progression, both cases have peculiarities that make them different. Which differences in the two cases do you think may inform treatment choices? Would the differences lead your choice of treatment in a different direction, or would both patients receive the same treatment? If treatment is different, what is the difference that changes your choice of treatment? The standard of care for non-small cell lung cancer with an EGFR mutation upon progression on first-line tyrosine kinase inhibitor is generally chemotherapy, possibly combined with immunotherapy. In non-small cell lung cancer with an EGFR mutation, there are multiple suggested mechanisms of resistance to osimertinib. These involve new mutations in the EGFR gene, alterations in parallel or downstream oncogenes, such as MET, KRAS, and PIK3CA, or histological transformation to small-cell carcinoma. MET amplification is a very common abnormality seen in those patients. Upon progression, patients have several options, and their treatment should be directed based on the results of the repeat molecular evaluation. That is why it is important to repeat a biopsy on patients with disease progression. Nowadays, liquid biopsy is also helpful in detecting these abnormalities without the need for an actual biopsy. Roberto can benefit from a MET-directed therapy using a tyrosine kinase inhibitor. He did receive stereotactic radiosurgery to the brain due to the presence of mild symptoms. He is clinically doing well, so the need to initiate immediate systemic cytotoxic chemotherapy is not urgent. In this patient, I would offer him an oral MET inhibitor and repeat his imaging in three months. On the other hand, the second patient, Heidi, did not have an actionable mutation upon re-biopsy. The patient is best served by a clinical trial. However, if a trial is not available, or if she is not eligible, then systemic chemotherapy and immunotherapy would be the standard of care. In my practice, and based on the results of the IMpower 150 trial, the use of the combination of carboplatin, paclitaxel, atezolizumab, and bevacizumab is preferred. The subset analysis of the EGFR-positive patients in this trial favored the use of the quadruplet combination. Thank you for listening to this episode of the ASCO eLearning Podcast. For more information on the treatment of non-small cell lung cancer, including additional patient cases and opportunities for self-evaluation, please visit the comprehensive eLearning center at elearning.asco.org. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make this part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

Dr. Doug Johnson is an Associate Professor of Medicine and Leader of Melanoma Program at the VanDr. Doug Johnson is an Associate Professor of Medicine and Leader of Melanoma Program at the Vanderbilt Ingraham Cancer Center in Nasheville, TN. In today’s ASCO eLearning Podcast, Dr. Johnson discusses two patient cases related to stopping of anti-PD-1 and consideration of retreatment for metastatic melanoma. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts [https://podcasts.apple.com/us/podcast/asco-elearning-weekly-podcasts/id1375021523] or Google Play [https://play.google.com/music/listen?u=0#/ps/Igjyhvqqrvuc5mjvlljhzkpvgeu]. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org [https://elearning.asco.org/].   The purpose of this podcast is to educate and inform. This is not a substitute for 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.   Hello, my name is Doug Johnson. I'm an associate professor of medicine and leader of the Melanoma Program at Vanderbilt-Ingram Cancer Center. Today we compare two patient cases that relate to stopping of Anti PD-1 therapy in consideration of whether to re-treat patients that have metastatic melanoma. These two cases have similarities, yet the recommended treatments may be different.   Let's look at the cases. Patient case one. Our first patient case is Dave. Dave is a 62-year-old man with metastatic melanoma involving the lungs and liver. He was treated with single agent nivolumab and he had decreasing size of one of his lung metastases but had increasing liver metastases when his first CT scan was performed.   Since his melanoma has a BRAF V600e mutation, he was switched to BRAF and MEK inhibitors, which were later followed by progression and 12 months on therapy.   Patient case two. Our second patient case is Rachel. Rachel's a 55-year-old woman with metastatic BRAF wild type melanoma involving the lungs and liver as well. She receives pembrolizumab with a complete response and therapy is stopped after 15 months of treatment.   Two years later, she has growth of two of her lung lesions and a biopsy confirms that this is melanoma.   So questions for consideration. As you can see, both cases involve progression of anti PD-1 therapy, but there are some differences. Do the differences lead your choice of treatment in a different direction, or would both patients receive the same treatment? In particular, would you consider anti PD-1 re-treatment for either or both of these patients?   Some background. The standard treatment for metastatic melanoma, regardless of BRAF mutation status, is Anti PD-1 monotherapy, either with nivolumab or pembrolizumab. Approximately 44% of patients experience complete responses to treatment, many of which are durable. Many patients with complete or near complete responses have a discussion with their oncologist and elect to stop treatment after one to two years on therapy. However, about one third of patients who have a response ultimately experience disease progression.   The treatments who either respond to Anti PD-1 and then later progress or patients who never respond at all is an important issue to consider. Options for these patients include ipilimumab monotherapy, ipilimumab in combination with nivolumab, or if BRAF mutated, BRAF and MEK inhibitor therapy. Re-treatment with Anti PD-1 may be an option as well.   Other melanoma therapies have shown benefit with re-treatment with this type of strategy. For example, patients re-treated with BRAF and MEK inhibitors, provided they took at least a six week break off therapy, have nearly a 50% response rate to re-treatment. In addition, patients who benefited from ipilimumab then later progressed had at least a 20% response rate to re-treatment.   So how are these cases related? Both patients experienced progression either on or following Anti PD-1 treatment. However, there are some key differences as well. Patient one progressed while still receiving treatment, and at least his liver lesions never responded to therapy at all.   On the other hand, patient two experienced progression a long interval after completing treatment. She also had an objective response, in fact, a complete response to her initial course of therapy.   So what should we do with these patients? Well, the answer, from my perspective, is patient one should not receive re-treatment with Anti PD-1 therapy. A recent publication by Dr. [? Betof ?] and colleagues in JCO studied 396 patients with long-term follow-up following Anti PD-1 treatment. This included 34 patients who were re-treated. None of the patients who initially progressed on therapy, so those who didn't have a complete response, were prolonged stable disease. None of those patients experienced long-term benefit with re-treatment.   On the other hand, these patients did benefit from ipilimumab and nivolumab 25% of the time, with a 25% response rate. Additional patients also experienced stable disease in this group. Thus, either ipilimumab and nivolumab or [INAUDIBLE] monotherapy should be considered for patient one.   Patient two, by contrast, had a durable complete response to therapy and progressed after completion of treatment. This patient could consider re-treatment with Anti PD-1. A study by Dr. Warner suggested that of patients in this position, those who had an initial objective response to treatment, only 15% of patients had objective responses. However, durable benefit was more frequently seen in patients who had complete or partial response to their initial course. Many patients had prolonged stable disease with re-treatment.   Thus, re-treatment could be considered in this patient. Or we would also be reasonable to think about ipilimumab and nivolumab combination or ipilimumab alone. That would also be appropriate for this patient.   In closing, thank you for listening to this week's episode of ASCO e-learning weekly podcast. For more information on treatment for metastatic melanoma, including additional patient cases and opportunities for self-evaluation, visit the comprehensive e-learning center at e-learning.asco.org. Thank you.   [MUSIC PLAYING]   Thank you for listening to this week's episode of the ASCO e-learning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at e-learning.asco.org.

Dr. Rodrigo Munhoz is a Melanoma/Sarcoma Oncologist at Hospital Sírio Libanês in São Paulo, Brazil. In today’s ASCO eLearning Podcast, Dr. Munhoz discusses two patient cases related to challenges and barriers to treating cancer in developing countries. While the two cases are similar, the recommended treatments can vary depending on social, economic, cultural, religious, patient knowledge and other aspects. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts or Google Play. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org   The purpose of this podcast is to educate and inform. This is not a substitute for 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. Hello, my name is Rodrigo Munhoz, and I'm a melanoma and sarcoma medical oncologist at Hospital Sirio Libanes in Brazil. Today, we compared two patient cases treated in Brazil that describe challenges related to the access to systemic therapies for advanced melanoma in developing countries. These few cases share similarities. Yet, the recommended treatments can be largely different based upon sociocultural and religious aspects, among other variables that influence patients' choices, including enrollment into clinical trials. Let's look at the cases. Our first patient is Paolo, a 49-year-old man diagnosed with metastatic melanoma with asymptomatic CNS involvement in addition to lung and subcutaneous metastases. The patient was diagnosed with an intermediate risk primary melanoma of the right arm without nodal involvement a couple of years before. He presented for treatment considerations following disease relapse in the form of M1d disease with normal serum LDH level. Decision was made to proceed with first-line treatment with a combination of ipilimumab and nivolumab, a treatment covered by his private insurance plan. And he's scheduled to receive the first dose. Our second patient case is Rachel, a 65-year-old woman diagnosed with metastatic melanoma harboring a BRAF mutation. Following initial surgical treatment for a high-risk primary melanoma with nodal involvement, she developed short-interval metastasis with CNS, liver, and lung lesions. Although immune checkpoint blockers and BRAF and MAC inhibitors were not provided through the public health system, a clinical trial with a triplet combination of a BRAF inhibitor, MAC inhibitor, and an anti-PD-L1 agent was offered. Following discussions about the clinical trial implications, potential adverse events, and additional aspects described in an informed consent form, the patient declined any additional form of therapy and decided to pursue alternative treatments and healing through religion. As you can see, both cases are very similar in presentation, but with considerable differences in terms of treatment options and decisions. How can differences in access limit the treatment decision-making process and affect the patient's prognosis? How can socioeconomic and religious barriers determine one's decision about enrollment into a clinical trial? Advances in systemic treatment options for melanoma, both in the form of target therapy and immunotherapy through immune checkpoint blockade, have deeply altered the scenario for patients affected by this challenging disease. As an example, in a recent randomized trial, 52% of the patients with advanced melanoma treated with a combination of nivolumab and ipilimumab and 44% of those receiving single-lesion nivolumab were alive at five years. Similarly, a pooled analysis of patients receiving dabrafenib and trametinib showed robust activity of BRAF and MAC inhibitors in metastatic disease with response rates approaching 70% and almost 35% of the patients alive at five years. The efficacy of these agents was also demonstrated in patients with CNS metastases. These advances were also noted in the adjuvant setting. In randomized trials that included a majority of patients with stage III disease, pembrolizumab, nivolumab, or dabrafenib and trametinib resulted in significant gains in recurrence-free survival. Yet, these major breakthroughs are not homogeneously available throughout the globe. And many countries still face restricted access and significant inequalities in the treatments made available to the population. As an example, in Brazil, systemic treatment options offered through the public health system, which covers 80% of the population, are still largely limited to cytotoxic chemotherapy with DTIC being the most frequently prescribed agent. In this setting, enrollment into clinical trials represents an effective way to partially overcome these hurdles, extend the offer of active agents, and reduce these gaps. However, the conduction of a clinical trial brings additional challenges. In the cases described here, although very similar in presentation, several aspects were determinant in both medical and patient decisions, which may lead to distinct outcomes. For patient one, a standard-of-care treatment in line with the best scientific evidence was offered and available. In the second case, optimal care was limited by access issues. In addition, despite the possibility of inclusion in a promising clinical trial, social and religious aspects were also determinant in the patient decision. Despite the advances in screening, diagnosis, and treatment of solid tumors, including melanoma, access inequalities pose major challenges and demand a global agenda. Clinical research is an effective tool in reducing gaps and disparities in developing countries, but also largely influenced by cultural, social, and religious aspects, as exemplified by the cases described in this podcast. Initiatives designed to optimize access in developing countries must encompass not only a framework adapted to provide value-based care, but also effective education and communication tailored to patient preferences, as an example, religious belief, and socioeconomic status in discussions of treatment decisions. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. For more information on the treatment of melanoma in global oncology, including additional patient cases and opportunities for self-evaluation, visit the comprehensive eLearning center at elearning.asco.org. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

In this month's ASCO eLearning Podcast, Dr. Helen Chew, Professor of Medicine and leader of the Clinical Breast Cancer Program at University of California Davis Comprehensive Cancer Center, brings us two patient cases on systemic therapy for metastatic triple negative breast cancer.  This podcast episode appears as a resource in ASCO eLearning's recently updated Genetics & Genomics course collection in the course Hereditary Breast and Ovarian Cancer Syndrome. Click the links to learn more about these courses, including CME and MOC credit details. If you are interested in purchasing a course or the entire collection, go to shop.asco.org Transcript Hello, my name is Helen Chew. I am Professor of Medicine and leader of the Clinical Breast Cancer Program at the University of California Davis Comprehensive Cancer Center. Today, we compare two patient cases on systemic therapy for metastatic triple negative breast cancer. Systemic therapy for metastatic triple negative breast cancer remains a challenge. The mainstay of therapy is cytotoxic chemotherapy. In March 2019, based on the Impassion130 trial, the anti-PD-L1 antibody, atezolizumab, was approved in combination with nab-paclitaxel for metastatic triple negative breast cancer that expresses PD-L1.  However, for triple negative breast cancer without PD-L1 expression, immunotherapy is not an option. In addition, there are many indications for genetic counseling and testing, including patients diagnosed with breast cancer at age 45 years or younger and patients with triple negative breast cancer diagnosed at age 60 years or younger. Results of genetic testing may influence treatment options in metastatic breast cancer. Before we explore treatment options, let’s look at two similar cases where treatment choices may differ. Can you identify the key differences? Let’s begin with Case 1, a 45-year-old woman with metastatic triple negative breast cancer to the liver and lungs. Two years earlier, she had received preoperative anthracycline and paclitaxel for a stage II, triple negative breast cancer. She had a limited family history of cancer and underwent genetic counseling and testing. No pathogenic mutations were found in a panel of genes associated with hereditary cancers.  At the time of her metastatic recurrence, biopsy of a liver lesion confirmed metastatic carcinoma, consistent with triple negative breast cancer. There was no PD-L1 staining. The patient received carboplatin and gemcitabine for 6 cycles. She now has disease progression. Case 2 is a 57-year-old woman who also has metastatic triple negative breast cancer involving the chest wall, liver and bones. Three years earlier, she had received adjuvant anthracycline and paclitaxel for a stage II, triple negative breast cancer. She had no family history of breast or ovarian cancer, but underwent genetic counseling and testing revealing a pathogenic germline BRCA1 mutation. At the time of metastatic recurrence, chest wall biopsy confirmed metastatic triple negative breast cancer with no PD-L1 staining. The patient received carboplatin for 6 cycles with an initial response.  Nine months later, she has disease progression. In each of these cases, what option would you recommend for subsequent therapy? The choices include additional chemotherapy, such as capecitabine, eribulin or vinorelbine, or a PARP inhibitor. In Case 1, the correct answer is chemotherapy, including any of the named options. This patient does not harbor a germline BRCA mutation so would not benefit from a PARP inhibitor. In Case 2, the correct answer is a PARP inhibitor. In both the OlympiAD and EMBRACA phase III trials, patients with germline BRCA mutations and previously treated HER2-negative metastatic breast cancer were randomized to either chemotherapy of physicians’ choice or to olaparib or talozoparib, respectively. Approximately 40-50% had triple negative metastatic breast cancer in these two trials.  Patients who received the PARP inhibitors had significantly improved progression-free survival compared to chemotherapy in both trials. Both PARP inhibitors, olaparib and talozoparib, are approved for patients with HER2-negative metastatic breast cancer who have germline BRCA mutations.  These two cases of metastatic triple negative breast cancer share similarities. Both cases met criteria for genetic counseling and testing, including the young age at diagnosis for Case 1 and the diagnosis of triple negative breast cancer at age 60 or younger in Case 2. Both cases were treated similarly at initial presentation and on metastatic recurrence.  However, the key difference is that no pathogenic mutation was detected in Case 1. In contrast, a germline BRCA1 mutation was found in Case 2.  PARP inhibitors are associated with improved progression-free survival compared to the chemotherapy given in the OlympiAD and EMBRACA trials in patients with germline BRCA mutations and HER2 negative, previously treated metastatic breast cancer.   In addition, although both cases received a platinum-based regimen at metastatic recurrence, the TNT trial revealed that only patients with germline BRCA mutations and triple negative metastatic breast cancer had improved progression-free survival with carboplatin compared to docetaxel. No difference in progression-free survival was seen in the trial population of triple negative metastatic breast cancer without a germline mutation. Thank you for listening to this week’s episode of the ASCO eLearning Weekly Podcast. For more information on the treatment of metastatic breast cancer, including additional patient cases and opportunities for self-evaluation, visit the comprehensive eLearning center at elearning.asco.org