Podcast appearances and mentions of Richard L Schilsky

In this episode, Richard L. Schilsky, FSCT, FASCO, FACP, MD, discusses his involvement with ASCO, ideas for making a more equitable health care system and thoughts on the current state of oncology. Welcome to another exciting episode of Oncology Overdrive :13 About Schilsky :24 The interview 2:50 How did you end up in medicine, in oncology and then in GI oncology? What was your path into this space? 3:01 What was it that drew you to becoming involved in ASCO and seeing where your journey would lie in that space? 9:15 What is something that surprised you in oncology in your career? Is there anything you can look back and think that was really shocking, or that was a major development that you never could have imagined happening in the cancer space? 14:14 How has COVID impacted what you've seen for your patients and your colleagues? 23:04 What do we need to do to work towards a more equitable health care system and more equitable cancer care for our patients? 28:07 Looking back at your career, do you think where we are now is where you expected? 33:24 If somebody could only listen to the last 2 minutes of this episode, what would you want them to take away? 40:11 How to contact Dr. Schilsky 41:26 Thanks for listening 42:13 Richard L. Schilsky, FSCT, FASCO, FACP, MD, is the former chief medical officer and executive vice president of ASCO. He is also the former chief of hematology/oncology in the Department of Medicine and deputy director of the University of Chicago Comprehensive Cancer Center. We'd love to hear from you! Send your comments/questions to Dr. Jain at oncologyoverdrive@healio.com. Follow us on Twitter @HemOncToday and @ShikhaJainMD. Disclosures: Jain reports she is a paid freelance writer for Lippincott. Schilsky reports no relevant financial disclosures.

Retiring ASCO Chief Medical Officer Dr. Richard L Schilsky gives a far-reaching interview with ASCO in Action podcast host ASCO CEO Dr. Clifford A. Hudis, who examines Dr. Schilsky’s trailblazing medical career, his leadership in ASCO and indelible mark on its research enterprise, and what he sees for the future of oncology. ASCO’s first-ever Chief Medical Officer even offers some friendly advice for Dr Julie Gralow, who starts as ASCO’s next CMO on February 15, 2021. In a touching tribute, Dr. Hudis also shares what Dr. Schilsky’s friendship and mentorship has meant to him personally, and suggests that Rich will still be supporting ASCO on critical priorities moving forward. Don’t miss this exchange with one of oncology’s greats! Transcript DISCLAIMER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. CLIFFORD HUDIS: Welcome to this ASCO in Action podcast brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insights into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. The ASCO in Action podcast is a series where we explore the policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for-- people with cancer. My name is Dr. Clifford Hudis. And I'm the CEO of ASCO and the host of the ASCO in Action podcast series. For today's podcast, I am especially pleased to have as my guest my friend, colleague, and mentor Dr. Richard Schilsky, ASCO's chief medical officer. Now, I am sure that many of our listeners have already heard that Dr. Schilsky will be leaving ASCO in February of 2021, retiring. However, I want to reassure everybody that even in retirement, he will continue to make contributions and provide leadership to all of us. And his illustrious and path-blazing career in oncology spanning more than four decades is not quite over thankfully. Rich is ASCO's first chief medical officer. And as such, he has made a truly indelible mark on all of us. He started with a proverbial blank piece of paper. The position had no precedent. It had no budget. It had no staff. But now after just eight years in the role, he has helped make the CMO a critically important position at the society. And I have to say that success is more than anything due to Rich's vision and his leadership. And that's some of what we'll be talking about today. So Rich, thank you very much for joining me today for what I hope is going to be a great casual but informative conversation about your amazing career, your unique role at ASCO, and maybe most importantly in the end what you see for the future of oncology not just in the United States, but around the world. Thanks for coming on, Rich. RICHARD SCHILSKY: Thanks, Cliff. It's great to be here today. CLIFFORD HUDIS: So with that, let's just dive right in and start at the very beginning. Rich, tell everybody why you decided to become an oncologist and maybe share a little bit about what those early days looked like for you and, in that context, what it was like to have cancer at the beginning of your career. RICHARD SCHILSKY: Well, I knew from an early age that I wanted to be a doctor. And in fact, I had written a little essay when I was in sixth grade as a homework assignment called My Ambition. And my mother had tucked that away in a scrapbook. And I found it a number of years ago. And on rereading it, it was quite amazing to me to see what I was thinking about even then. Because I said not only did I want to be a doctor, but I didn't think that was enough, that I wanted to be a medical researcher because I wanted to discover new information that would help people heal from whatever their diseases might be. And so it was never really any doubt in my mind that I would be a physician. I went to medical school at the University of Chicago. But I was living in New York City at the time having grown up in Manhattan. And the only year we had off in medical school, the only time we had off in medical school, was the summer between the end of the first year and the beginning of the second year. So during that time, I went back to Manhattan. And I was able to get a fellowship from the American College of Radiology that allowed me to essentially hang out in the radiation therapy department at New York University Medical Center, which was within walking distance of where I grew up. And so I would go over there every day. And I was taken under the wing of a young radiation oncologist. And of course, I wasn't really qualified to do anything at that point except to follow him around, talk and listen to the patients. But that turned out to be a really formative experience for me because we saw the whole gamut of cancer. We saw head and neck cancers. We saw lung cancer. We saw patients with breast cancer and prostate cancer. And in those years-- this is the early 1970s-- many of these patients have fairly locally far advanced disease and were quite debilitated by it. But listening to their stories, hearing about their hopes and their struggles, really demonstrated to me the human side of cancer. So I went back to school and thought about this in the context of my own personal experience, which dated back to when I was in college when my mother's mother, my maternal grandmother, was diagnosed with breast cancer. This was 1968. And as you well know, there were very few therapies available for breast cancer in the late 1960s, mostly hormone therapies. And my grandmother had the treatment that was considered standard of care at that time, which was extended radical mastectomy followed by chest wall radiation. And some years after that first mastectomy, she had a breast cancer that developed in the opposite breast and had a second extended radical mastectomy and chest wall radiation. And these were very traumatic and disfiguring procedures for her to go through. Anyway, long story short is after another few years, she developed bone metastases and then brain metastases. And there was really very little that could be done for her other than hormone therapies. And having observed her go through that illness and realizing how limited our treatment options were and then having the experience after my first year in medical school pretty well cemented for me that I wanted to be an oncologist. I thought actually about being a radiation oncologist. But then I did my internal medicine rotation in medical school, fell in love with internal medicine. And that sort of put me on the path to be a medical oncologist. The clinical challenge of caring for cancer patients, the emotional attachment to those patients, and, of course, even then, the unfolding biology of cancer was so intellectually captivating that I actually applied for oncology fellowship when I was a senior medical student. So even before going off to do my medical residency, I had already been accepted as a clinical associate at the National Cancer Institute to start two years hence. And that's how I became an oncologist. CLIFFORD HUDIS: So it's so interesting. Because, of course, the story I'm sure for many people interested not just in oncology, but even medical education, there are little things that don't happen nowadays that happened with you like that last little vignette about the early acceptance into an advanced training program before your fellowship among other things. Can you remind us about the timeline? Because I think one of the things that many of our listeners often can lose sight of is just how new oncology really is as a specialty. ASCO itself founded in 1964. And the first medical oncology boards were mid-'70s, right? So you were in med school just before that second landmark, right? RICHARD SCHILSKY: That's right. I graduated from medical school in 1975. I started my oncology fellowship in 1977. And I got board-certified in medical oncology and joined ASCO in 1980. And so that was the time frame at that point. CLIFFORD HUDIS: So the internal medicine was actually, if I heard you right, just two years, not the now traditional four. RICHARD SCHILSKY: Yeah. I was a short tracker. I did only two years of internal medicine training rather than three. I did my training at Parkland Hospital and University of Texas Southwestern in Dallas with at that time a legendary chair of medicine, Don Seldin, who I had to get permission from him to leave the program prior to completing the third year of residency because I had already been accepted into fellowship at NCI. And he, Seldin, who was a brilliant chairman and a brilliant nephrologist, was not at all interested in cancer. And it took a bit of-- I was going to say arm twisting, but it really took bleeding on my part to get him to agree to allow me to leave the residency program to go to the NCI. But he eventually agreed. And in those years, the first-year clinical fellowship at the NCI was like being an intern all over again. There were about 15 of us. We were on call overnight in the clinical center once every two weeks. We cared for all of our inpatients as well as had a cadre of outpatients. We did all of our own procedures. We had no intensive care unit. So patients who were sick enough to require ventilator support, we cared on the floor in the inpatient service on our own with guidance from senior oncologists. It was a bit different from the way it is now. But, of course, it was fantastic on-the-job training because we just learned a ton and had to learn it very quickly. CLIFFORD HUDIS: So that's actually a great segue to the advances because there was a lot to learn then. But, wow, there's a lot more to learn, I think, now. And I have real sympathy for trainees and younger oncologists for the breadth of what they need to learn. Again, just testing your memory, but platinum came along pretty much in the mid-'70s as well, right? That was a pivotal expansion of the armamentarium for us. So what do you see-- when you summarize progress in cancer research and care over these decades, what do you think are the most pivotal or revolutionary milestones that you identify over the span of your career? RICHARD SCHILSKY: Yeah. It's really interesting to think about it historically. There were the early years of discovery in oncology from the 1950s to the 1970s when we really had the introduction of the first chemotherapy drugs and the miraculous observation that people with advanced cancer could actually obtain a remission and, in some cases, a complete remission with chemotherapy and combination chemotherapy in particular. And so that was the formative years of oncology as a medical specialty and really proof of concept that cancer could be controlled with drugs. When we got into the 1980s, 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. So I think that clearly understanding the biology of cancer as we do now and all that it took to lead us to that point, which was a combination of understanding biology, developing appropriate technology that would, for example, enable the sequencing of the human genome and then the cancer genome. And the other formative technology in my opinion that really changed the way we care for cancer patients was the introduction of CT scanning. When I was still a fellow at the NCI, we did not have a CT scanner. If we needed to get detailed imaging of a patient, we did tomography. And if you remember what tomograms looked like, they were really blurry images that you could get some depth perception about what was going on in the patient's chest or abdomen. But they really weren't very precise. When CT scanning came along, it really revolutionized our ability to evaluate patients, assess the extent of disease, stage them in a much more precise way, which then allowed for better patient selection for curative surgery, better radiation therapy planning. So we don't often point to imaging advances as some of the transformative things that paved the way in oncology, but I think imaging is really overlooked to some extent. So I think the technology advances, the biological advances, are the things that really allowed the field to move forward very quickly. And by the time we got into the mid-1990s, we were beginning to see the introduction of the targeted therapies that have now become commonplace today. And then it was around 2000, I think, that we saw the introduction of Gleevec. And I'm reminded always about an editorial written by Dan Longo in The New England Journal a few years ago. And Dan and I were fellows together. We worked side by side on the wards at the clinical center and became very good friends. And Dan in his role as a deputy editor of The New England Journal wrote an editorial a few years ago that was titled "Gleevec Changed Everything." And Gleevec did change everything. It changed our entire perception of what were the drivers of cancer and how we might be able to control cancer very effectively and potentially put it into long-term remission. Now, of course, we know now that the whole Gleevec story is more of an exception than a rule in targeted therapy. And, of course, we know that tumors become resistant to targeted therapies. But we couldn't have known any of this back in the early years of oncology because we had no real insight into what caused cancer to grow or progress. And the notion of drug resistance, while we realized that it occurred, we had no idea what the mechanisms were. So it's such a different landscape now than what it used to be. It's quite remarkable. CLIFFORD HUDIS: So as you tell the story, there's, of course, a lot of focus on technology, whether it's biology and understanding the key features of malignancy or imaging or more. But what I also note in your story and I want to come back to is the people. And I can't help but reflect on where we are in this moment of the COVID-19 pandemic. Yes, we've moved to telemedicine. Everything can be accomplished via technology. And, yet, the human touch is so important. When we think about being in the room with people, when we think about face to face from the context of career development and your own career, you touched on Dr. Seldin, I think, already from the perspective of internal medicine training. But are there are other mentors or important shapers of your career that you think we should know about? RICHARD SCHILSKY: Well, probably, the most influential person early in my career in medical school was John Altman. John, you may know, was the inaugural director of the University of Chicago's NCI-designated Cancer Center, which was one of the very first NCI-designated cancer centers in 1973 after the National Cancer Act of 1971 created the cancer centers program. And John, who was a leading oncologist studying Hodgkin and non-Hodgkin's lymphoma, was a faculty member there. He was the director of our cancer center as I said. He took me under his wing even when I was in medical school and served as a real role model and mentor to me. When I was in my internal medicine training as I mentioned earlier, Don Seldin, the chair of medicine, was never particularly interested in oncology. So, to some extent, I didn't have-- I had great internal medicine training. But I did not have good mentorship in oncology. When I got to the NCI, then my whole world really opened up. And the two pivotal people there in my career were Bob Young, who was chief of the medicine branch and was my clinical mentor and remains a mentor and friend to this day, and then, of course, Bruce Chabner, who was the chief of the clinical pharmacology branch. And in my second year of fellowship when we all went into the laboratory, I went into Bruce's lab. And that's where I really got interested in the mechanism of action of anti-cancer drugs and ultimately in drug development and early phase clinical trials. And both Bob and Bruce remain very close to me even today. CLIFFORD HUDIS: So I'm concerned about time on our call today on our discussion. Because we could obviously fill lots of hours on all of these remarkable experiences and amazing people you worked with. But I'm going to ask that we fast forward a little bit. You and I share, I think, passion and love for ASCO. So I think that it's reasonable for us to focus a little bit on that for the time we have left here. You didn't start out obviously as chief medical officer at ASCO. But you were a really active ASCO volunteer and leader. Maybe tell us a little bit about some of the ASCO volunteer roles that you engaged in and what that meant to you at the time and how that led to this role. RICHARD SCHILSKY: Well, I'll be brief. I joined ASCO in 1980 at the first moment that I was eligible to join ASCO. I had attended my first ASCO meeting the year before, 1979, when I was still in my fellowship training. And it was clear to me even then when the whole annual meeting was about 2,500 people in two ballrooms in a hotel in New Orleans that that was a community of scholars and physicians that I wanted to be a part of. And so, over the years, I did what people do even today. I volunteered to participate in whatever ASCO activity I could get involved with. Over the years-- I think I counted it up not too long ago-- I think I served or chaired 10 different ASCO committees, more often serving as a member, but in a number of those committees also serving as the chair over many years. And as I became more deeply involved in ASCO and saw other opportunities to engage, I had the opportunity to run for election to the board and was-- after a couple of tries was elected to serve on the board and then eventually elected to serve as ASCO president in 2008-2009. But the attraction of ASCO in many ways was a community of diverse but, in many ways, like-minded people, people who had similar passion and drive and focus. But I think what you get at ASCO in many ways is the wonderful diversity of our field. If you work in a single institution for much of your career as I did and as you did, you get to know that institution pretty well. You get to know its perspectives and its biases and its strengths and its weaknesses. But there's a whole world of oncology out there. And you can get exposed to that at ASCO because you meet and work with colleagues from every clinical setting, every research setting, people who have remarkable skills and interests and passions. And it's just a wonderful environment to help develop your career. So I consider myself to be extremely fortunate to have had the journey in ASCO that I've had culminating, of course, with ultimately my coming on the staff as ASCO's first chief medical officer. CLIFFORD HUDIS: We often joke about that blank sheet of paper. But in retrospect, it's very obvious that you had built up that collection of LEGO blocks, and then you assembled them all into the ASCO Research Enterprise, a name you gave it. And it really, in retrospect, builds, I think, very cleanly upon all of your prior experience, but also the vision that you developed based on that experience for how research should be conducted. Can you maybe share with everybody the scope and vision for the ASCO Research Enterprise, what the intent was, and where you see it going, and what it includes today? RICHARD SCHILSKY: Sure. I won't claim that I came to ASCO with the whole thing fully developed in my mind. As you said, when I came, I literally did have a blank slate. Allen Lichter, who hired me, said, come on board and help me make ASCO better. And so I, in a sense, reverted to what I knew best how to do, which was clinical research. And having in my career been a cancer center director, a hem-onc division chief, a cooperative group chair, I had a lot of experience to draw on. And it was obvious to me that ASCO was fundamentally an organization that took in information from various sources, evaluated it, vetted it, collated it, and then disseminated it through our various channels, most notably our meetings and our journals. But ASCO itself did not contribute to the research enterprise. And that seemed to me to be a lost opportunity. We knew that ASCO had lots of data assets that could be of interest to our members and to the broader cancer community. But they were scattered all around the organization and not particularly well annotated or organized. So we began to collate those. And they are now available to ASCO members on the ASCO data library. I recognized that we did not have an organized unit in ASCO to support or facilitate or conduct research. So, in 2017, we formed the Center for Research and Analytics and brought together staff who were already working at ASCO but scattered in different departments but all people who had an interest in clinical research or research policy and brought them into this new unit, which has really become the focal point for research work at ASCO. We recognized that ASCO members for many years were interested in surveying their colleagues, surveying other ASCO members, to help advance research questions. But ASCO actually had a policy that prohibited that. So that never really made good sense to me. It seemed like a lost opportunity. And we were able to create a program and have the ASCO board approve it whereby any ASCO member could opt in to participate in what we now call the Research Survey Pool. And in doing so, they are essentially agreeing to participate in research surveys conducted by their colleagues. So that program is now up and running. There are, I think, eight surveys that have been completed or are currently in the field. And this is now a service that ASCO provides through CENTRA to its members to enable them to survey their colleagues for research purposes. Most importantly, I think we saw an opportunity back in 2014 or 2015 to begin to learn from what our colleagues were doing in clinical practice as they began to deploy precision medicine. And there was a lot of genomic profiling that was going on at that time. It was revealing actionable alterations in roughly 30% or so of the tumors that were profiled. But there was a lot of difficulty in doctors and patients obtaining the drugs that were thought to be appropriate to treat the cancer at that particular time because most of those drugs would have to be prescribed off label. And there was not a sufficient evidence base to get them reimbursed. And, moreover, even if they could be reimbursed, there was no organized way to collect the patient outcomes and learn from their experiences. So that led to us developing ASCO's first prospective clinical trial, TAPUR, which really solves both of those problems. Through the participation of the eight pharmaceutical companies that are engaged with us in the study, we are providing-- at one point, it was up to 19 different treatments free of charge to patients. These are all marketed drugs but used outside of their FDA-approved indications. And we were collecting data on the patients, the genomic profile of cancer, the treatment they received, and their outcomes in a highly organized way. And so now this is a study that we launched in 2016. We're now almost to 2021. We have more than 3,000 patients who have been registered on the study, meaning consented to participate, more than 2,000 who have been treated on the study. And we are churning out results as quickly as we can about which drugs are used or not useful in the off-label setting for patients whose tumors have a specific genomic profile. So we built all this infrastructure. And having this in place has also then allowed us to respond rapidly to unmet needs. So when the COVID-19 pandemic overwhelmed all of us, and when our members were looking for information about what was the impact of COVID-19 on their patients, one of the things we were able to do because we had CENTRA, because we had a skilled staff and an infrastructure, was to very quickly stand up the ASCO COVID-19 registry, which we launched in April of this year. And there are now about 1,000 patients who've enrolled in the registry from around 60 practices that are participating. And we will follow these patients now longitudinally and learn from their experiences what has been the impact of the COVID-19 illness on them and their outcomes, how has it disrupted their cancer care, and ultimately how that impacts their overall cancer treatment outcomes. So as I now contemplate leaving ASCO after eight years having started with a blank slate, I'm very proud of the fact that I think I'm leaving us with a remarkable infrastructure. We now have a clinical trials network of 124 sites around the country participating in TAPUR that we never had before. We have through the work of CancerLinQ a real-world evidence data generator that is beginning to churn out valuable insights. We have a capacity to survey ASCO members for research purposes. We have an ability to stand up prospective observational registries to gather information longitudinally about patients and their outcomes. We have a core facility in CENTRA with highly skilled data analysts and statisticians that can support these various research activities. So ASCO is now primed, I think, to really contribute in a very meaningful way to the gaps in knowledge that will forever exist in oncology just because of the complexity of all the diseases we call cancer. And that's what I mean by the ASCO Research Enterprise. It is in fact remarkable and, I think, powerful enterprise if we continue to use it effectively. CLIFFORD HUDIS: Well, that's an interesting segue to my next thought, which is really about what comes next. I'll talk about you. But let's start with ASCO first. Your successor, Dr. Julie Gralow, obviously has been announced publicly. She's an accomplished clinician and researcher. She has a known recognized passion for patients, patient advocacy, clinical research through her leadership at SWOG but also health care equity and global oncology. So from your perspective, having created all of these assets and resources, what advice would you give Dr. Gralow publicly on how to make the position hers, what to take us to next? And I do want to acknowledge for everybody listening that the hints I've been making up until now are that Rich has agreed that he will continue to contribute as a leader to TAPUR for the short term, at least, at least the next year helping Julie get fully oriented to this program and others. So what will your advice be to Julie? RICHARD SCHILSKY: That's a great question. She's a great selection. And congratulations on hiring her. I think there are two key issues, I think, maybe three. One is to have a broad scope and cast a wide net. Oncology care and cancer research and cancer biology are incredibly complicated and nuanced and broad in scope. And although Julie is an accomplished breast cancer clinician and researcher, in this role at ASCO, you have to be very broad. You have to understand all of cancer care, all of cancer research, all of policy and advocacy not as an expert in necessarily in any one aspect of ASCO's work, but you have to understand the impact of all of those things on cancer care providers and on cancer patients. And it's important to always be looking to the future. The future is going to be here before you know it. And we as a professional society have to prepare our members for that future. So that leads me to the second point, which is listen to the members. The members are the people on the front lines who are delivering care to patients every day. And, fundamentally, ASCO's job is to be sure that our members have all the tools and knowledge and resources that they need to deliver the highest quality care to patients every day. So listening to what they need, what their struggles are, what their burdens are, is extremely important. And then the third thing I would recommend to her is that she get to know the staff and colleagues that she'll be working with. ASCO has a remarkably accomplished, skilled, motivated, passionate staff, many of whom have been with the organization for years, if not decades, who understand what ASCO can and cannot do and who understand what our members need. And she will be well advised to spend a good portion of her first few months on the job just listening and learning from her colleagues. CLIFFORD HUDIS: That's always good advice for anybody making a big career move. But, of course, the wisdom you bring to it is palpable and much appreciated. And I'm sure Julie will be taking your advice. And, by the way, so will I continue to do that even after you make your move. So speaking of your retirement, can you share with us a little bit about what it's actually going to look like for you? Is it about family? Or are you still going to have some professional engagement? Again, I suggest that there might be some already, but maybe you could expand on it. RICHARD SCHILSKY: Yeah. I'm still fully focused on my work at ASCO. And, of course, as you know, when I wake up on February 15, I will no longer be ASCO's chief medical officer. And it's going to be a bit of a rude awakening. Fortunately, I will be able to continue my engagement with ASCO through the TAPUR study as you mentioned. I will, of course, forever be at ASCO member and a donor to Conquer Cancer and be willing to serve the society in any way. I have a number of activities that I've been involved with even throughout my time at ASCO. Not-for-profit boards, for example-- I'm on the board of directors of Friends of Cancer Research. I'm on the board of directors for the Reagan-Udall Foundation for FDA. I plan to continue with those activities as long as they'll have me. I've been serving the last few years on the board also of the EORTC, the large European cooperative clinical research group. And I expect to continue in that role. Beyond that, I will see what opportunities come my way. I think one of the things about retirement if you will that I'm looking forward to is the opportunity to pick and choose what to work on based on what interests me without having the burdens of having a full-time job. On the personal front, of course, we're all looking forward to crawling out from the pandemic. I've basically been locked in my home outside Chicago since March. And I'm looking forward to getting back out to a little bit of a social life. As you know, I have two grown daughters and now three grandchildren, two of whom are in Atlanta, one of whom is near by us in the Chicago area. So looking forward to spending time with them as well. So it will be a change for me to be sure after working as hard as-- I feel like I've worked for really now 45 years since I graduated from medical school. But I also feel like I'm not quite done yet and that I still have ways in which I can contribute. I just feel like at this point, maybe it's time for me to choose how I want to make those contributions and spend a little bit more time doing some other things. CLIFFORD HUDIS: Well, both you and my predecessor, Allen Lichter, are modeling something, have modeled something, that I think is not often discussed but can be very important. For people and for institutions, change is not a bad thing. And setting the expectation that you will pour your heart and soul into something but not necessarily do it alone or forever and not prevent others from taking that role at some point, that's a really-- I think it's a selfless kind of sacrifice in a way. Because, of course, you could stay and do what you're doing for longer. But as you and I have discussed, there is a value for all of us collectively in having fresh eyes and new people take organizations in a new direction. That's how I ended up here frankly. And I think that's the kind of opportunity you're creating right now, something that should be celebrated in my opinion. RICHARD SCHILSKY: Well, thanks. And I couldn't agree more. When I look back at the arc of my career and having all the different kinds of leadership roles that I've had, I basically have made a job change every 8 to 10 years. I was the director of our cancer center for nearly 10 years. I was associate dean for clinical research at the University of Chicago for eight years, another position that I created from a blank slate at that institution. The exception was serving 15 years as a CALGB group chair. But that was a position I really loved and enjoyed and felt like at the end of the first 10 I hadn't quite accomplished everything I wanted to accomplish. But the point is that I think it is both necessary for organizations to have regular leadership change. And it's also refreshing for us as individuals. There gets to a point where you feel like you can do your job in your sleep. And I actually think that's a good time to make a change. Because if that's the way you feel, you're not being sufficiently challenged. And you're probably not being sufficiently creative. And so it's a good time to move on and refresh your own activities and give your organization a chance to bring in someone to hopefully build on whatever you've created and bring it to the next level. CLIFFORD HUDIS: Well, I agree with all that, although I think your comment there about doing the job in your sleep would not apply because I'm pretty confident that the environment and opportunities have continued to evolve in a way that has made it interesting from beginning to end. But you don't have to rebut me on that. I just want to thank you very, very much, Rich. As we set up this podcast, I expected that we would have a really fun and enlightening conversation. And, of course, you did not disappoint. We could talk for much, much longer if we only had the time. On a personal note to you and for the benefit of our listeners, I want to share that Rich has been for me a remarkable friend and mentor and colleague. I first met Rich at the very beginning of my career when my mentor, Larry Norton, pushed me out from Memorial into the larger world. And he did that first and primarily through ASCO and the Cancer and Leukemia Group. Those are really the two places where I was exposed to the world. And through the CALGB, Rich really began to offer me and others, many others, opportunities that shaped careers plural, mine and others. So when I got to ASCO as CEO, Rich was there. And I knew I could always depend on you to be clearheaded, intellectually precise, constructive, visionary. And the thing about you, Rich, is that you never would say yes to anything unless you knew for sure you could do it and indeed, I think, how you could do it. I always share this story which your staff at CENTRA pointed out to me. And I have to admit that I hadn't picked it up myself. But in all the years of now working down the hall from Rich, probably hundreds and hundreds of hours of meetings, he never has taken a note in front of me. And, yet, everything we talk about, every action item we conclude to pursue, they all get done. So I don't know, Rich. You have a remarkable way of organizing your thoughts and your plans, keeping it together, and getting things done. And I'm going to miss that tremendously in the years ahead. So, Rich, I want to say congratulations. Congratulations on reaching this really important milestone in your life. Thank you on behalf of ASCO and the broader oncology community and the patients we care for and their families for making the world a better place. And just as a small thing, thank you for joining me today for this ASCO in Action podcast. RICHARD SCHILSKY: Thank you, Cliff. It's been great. CLIFFORD HUDIS: And, for all of you, if you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts or wherever you listen. And, while you're there, be sure to subscribe so you never miss an episode. The ASCO in Action podcast is just one of ASCO's many podcasts. You can find all of the shows at podcast.asco.org. Until next time, thank you for listening to this ASCO in Action podcast.

Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA4 with Dr. Hedy Kindler. Welcome to the ASCO Daily News podcast. I'm Dr. Richard Schilsky, Senior Vice President and Chief Medical Officer of ASCO. I'm pleased to be joined by Dr. Hedy Lee Kindler, Professor of Medicine at the University of Chicago Medicine where she is Associate Vice Chair for Clinical Research in the Department of Medicine as well as Director of the Mesothelioma Program. Dr. Kindler presented abstract LBA4, olaparib as maintenance treatment following first-line platinum-based chemotherapy in patients with a germline BRCA mutation and metastatic pancreatic cancer, Phase III POLO trial during the plenary session. Dr. Kindler, welcome to the podcast. Thank you for inviting me to share the results of our study. The five-year survival rate for people with metastatic pancreatic cancer is still less than 5%. So there's a real sense of urgency to develop new treatments. The POLO trial evaluated the efficacy of maintenance treatment with olaparib, a PARP inhibitor in patients with metastatic pancreatic cancer and a germline BRCA1 and/or BRCA2 mutation. What did the study show? Well, in this study, patients with metastatic pancreatic cancer with germline BRCA1 or 2 mutations who had received at least 16 weeks of a first-line platinum-based chemotherapy were randomized 3 to 2 to olaparib tablets or a placebo. The primary endpoint was progression-free survival by blinded independent central review. This study showed that maintenance olaparib provided a statistically significant and clinically meaningful improvement in progression-free survival. The progression-free survival was 7.4 months with olaparib and 3.8 months for placebo, with a hazard ratio of 0.53 and a p-value of 0.038. Progression-free survival on olaparib was the same irrespective of whether patients had stable disease or a complete or partial response to first-line chemo. From six months onwards, more than twice the proportion of olaparib arm patients were progression-free compared with the placebo arm. 23% of patients had a response to olaparib. And what is truly remarkable is that the median duration of response to olaparib treatment in these patients with metastatic pancreatic cancer was over two years. The interim survival data at 46% maturity showed no difference between arms. And final survival results will be evaluated at 46% maturity. Health-related quality of life was preserved with olaparib treatment and showed no difference between arms. And maintenance olaparib was quite well-tolerated with an AE profile similar to that seen in other tumor types. So those are really quite exciting results. One question I had in looking at the study design is that, as you mentioned, patients in the trial all received four months of standard chemotherapy and were then randomized to continue treatment with placebo or olaparib. The question is, is it standard practice to stop active cancer treatment after four months? Would there be some rationale to adding olaparib to standard chemotherapy rather than using it as maintenance? Actually, they did not. Patients had at least 16 weeks of first-line platinum-based chemotherapy with no maximum limit to the duration. Actually, about a third of patients received more than six months of chemotherapy. This was up to the treating physician and the patient. And remember, in their cord 11 trial, the median number of cycles was 10. Continuing on folfirinox does increase cumulative toxicity, principally myelosuppression and neuropathy. So it is a very reasonable thing to want to switch to a potentially less toxic treatment. Understood. Thanks for that clarification. So you asked about whether one could combine olaparib with standard chemotherapy. Unfortunately, myelosuppression at greater than anticipated rates is the common experience of combinations of olaparib and other PARP inhibitors with chemotherapy. For example, in a phase I trial of olaparib plus gemcitabine, which had a pancreatic cancer expansion cohort, it was not possible to administer gemcitabine above a dose of 600 mg per meter squared or olaparib above a dose of 100 mg bid. So it's quite unlikely that a combination of the highly myelosuppressive, folfirinox, could be administered safely with olaparib. So if I'm understanding you correctly though, there were a proportion of patients in this study who continued chemotherapy beyond four months but also then had olaparib added during that period of time? They had chemotherapy for four months or greater and then, they stopped chemotherapy and at that point, were randomized to receive either monotherapy with olaparib or placebo. There was no combination of chemotherapy plus olaparib. Sorry, for not being able to follow this as clearly as you've laid it out. So what was the trigger to discontinue the chemotherapy then leading them to the randomization to olaparib or placebo? That was investigator and patient choice. Some patients wanted to receive only four months of chemotherapy and switch over, others wanted to continue chemotherapy for longer. Remember, there is no standard of care, particularly at the time that the study was initiated, for maintenance chemotherapy. And so, four to six months of chemotherapy, at the time of the study design, was considered a very reasonable option. Were all of the patients not progressing at the time of randomization? Correct. All patients were required to have stable or responding disease at the time of randomization. OK, so I wanted to ask you about the germline mutations in BRCA1, BRCA2. We commonly think of BRCA mutations as being associated with breast or ovarian cancer and maybe a few other cancer types, but how often is it that a patient with pancreatic cancer will be a carrier of a germline BRCA mutation? Studies have shown that between 4% and 7% of pancreatic cancer patients harbor a germline BRCA1 or 2 mutation. In view of the results of this study, now, do you feel that all patients with metastatic pancreatic cancer should be tested for a germline BRCA mutation? Well, given the treatment implications demonstrated in the POLO trial, I think it is incumbent upon oncologists to offer all pancreatic cancer patients the option of germline testing. This is supported by an ASCO provisional clinical opinion from January of 2019, which recommended that patients with pancreatic cancer undergo risk assessment for hereditary syndromes that increase pancreatic cancer risk. It states that germline genetic testing for cancer susceptibility, including testing for BRCA mutations, may be discussed with individuals diagnosed with pancreas cancer even if family history does not clearly suggest an inheritable cancer-related syndrome. Similarly, the NCCN now recommends germline testing for all patients with pancreas cancer due to data that demonstrates that germline mutations can occur at a similar rate in pancreas patients with or without a family history of any type of cancer. Thanks. So one final question for you. Given the difficulty that we've had in developing effective new treatments for pancreatic cancer patients, given the lack of effective targeted therapies, this study would seem to open up new possibilities. But as someone who's an expert in the field, what do you see as being on the horizon in pancreatic cancer research? This is an exciting trial because it's the first phase III randomized study to establish a biomarker-driven approach in the treatment of metastatic pancreas cancer. And while I hope that it will open the door to a new era of personalized care for this disease, I think we've been burned many times before. It's so common, in this disease, to see superimposable KM curves. And so, when one sees a hazard ratio of 0.53, it's genuinely exciting. But I really would not hazard a guess as to where we are going next. It's fraught with too many problems. Understood. Again, today, my guest has been Dr. Hedy Kindler of the University of Chicago Medicine. Hedy, thank you so much for being on the podcast with me. Thank you, Rich. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple podcast.

Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA3 with Dr. William Tap. Welcome to the ASCO Daily News podcast. I'm Dr. Richard Schilsky, senior vice president and chief medical officer of ASCO. I'm pleased to be joined today by Dr. William Tap, a medical oncologist and chief of the sarcoma medical oncology service at Memorial Sloan Kettering Cancer Center. He presented abstract LBA3 at the plenary session reporting results of the ANNOUNCE trial, a randomized placebo controlled double blind phase three trial of doxorubicin plus olaratumab versus doxorubicin plus placebo in patients with advanced soft tissue sarcomas. Dr. Tap, welcome to the podcast. Thank you so much, Dr. Schilsky. I really appreciate the opportunity to talk to you today and also to have had the opportunity to present these data at ASCO during the plenary session. Olaratumab, a PDGFR alpha antagonist, in combination with doxorubicin was approved by the FDA in 2016 for patients with advanced soft tissue sarcomas who are not candidates for curative radiotherapy or surgery. A phase two trial showed a significant improvement in overall survival for olaratumab plus doxorubicin versus doxorubicin monotherapy. The ANNOUNCE study was designed as a phase three trial to confirm overall survival of this treatment combination. However, the study did not meet its primary endpoint. What are some possible explanations for the difference in outcomes in the phase two and phase three trials? I think that's such an important question. The results of the ANNOUNCE study have really only become available within the last few months. So therefore, at this time, there is a really large and concerted effort that is ongoing to really understand them, not only as they stand alone, but as you mentioned in the context of the phase 1B two result that led to accelerated approval. First of all, we have not found any noted discrepancies in study conduct or data integrity which could explain these findings or really discrepancies between the two studies. That's the really important initial fact. There were some notable differences between the two studies. And I know it's not great to compare two studies. But, for instance, the phase 1B two study was not blinded or did not have a placebo. It had progression free survival as a primary endpoint. There were no subtype specific analyses. And it was a relatively small study, just about 10 sites in the United States. Patients tended to be pretty healthy. But because it was just a signal finding study, many patients were coming on at later lines in therapy. There was no loading dose in the phase 1B two study. And cardio protectants, because we tended to push higher doses of doxorubicin, were used generally after patients received about 300 milligrams per meter squared. This is very different when we think about the phase three study, which again was double blinded, placebo controlled with an overall survival primary endpoint. And what's important is that this primary endpoint was a dual primary endpoint that looked at overall survival in the total soft tissue sarcoma population, but also within the leiomyosarcoma population. So we were actually looking within these two populations. And the study could have been positive if we met either of those primary endpoints. This was a large study, over 110 international sites. And it was rapidly accruing study. So there are some of these differences that are very notable. When we start to think of the differences of why we could have seen the outcomes, the first plausible explanation is that it is possible that olaratumab does not have activity in soft tissue sarcomas. But we would then have to question, why did we see such striking results within the phase 1B two trial. And it's hard to say exactly what that would have been, but it may have been to the small sample size. As you know, sarcoma really represents 50 to 80 different subtypes. And in the sarcoma community, we now look at these as potentially very different diseases with different biology. So you begin to bring in many different histologies or many different diseases into a clinical trial, and that could also explain some of the results that we saw, as these diseases often have really disparate clinical behavior. The other thing is that with an overall survival endpoint, which is a composite primary endpoint, it is possible that subsequent therapies on the phase two study may have really also affected outcomes when we looked at overall survival. We know there have been a lot of advances in many of the very specific sarcoma subtypes. And this potentially could have affected outcomes or even there could have been some chance in a smaller phase two study. The other thing that's very possible is that olaratumab has some activity in soft tissue sarcomas in general, but the outcomes were really missed in the phase three study. And this could possibly be again due to the heterogeneity of the study population, not only with the different sarcoma subtypes, as mentioned, but also within sarcoma subtypes. A disease like leiomyosarcoma can actually be a very heterogeneous disease. The other thing, as mentioned before, there could have been some differences in trial design that contributed or how the ANNOUNCE control arm did in this study. So this was not an upfront study, but still for single agent doxorubicin had one of the highest overall survival benefits for doxorubicin alone noted in any phase three clinical trial. Just to name a few final things, there were a lot of subset analyses that are being done and were done on the phase three study. It did, interestingly, point out two things. One is that patients who had a lower albumin tended to do better with the combination of olaratumab, which suggested the possibility that maybe olaratumab with doxorubicin could work better in sicker patients. And understanding this population in the phase three study seemed to be a healthier patient population in the phase two. That could have affected it. And there were some very interesting trends when we looked at PDGFR alpha signaling. And this is something that we're very interested in. And although exploratory, we're still looking very closely. But overall, PDGFR alpha positive tumors tended to do worse than PDGFR negative tumors. And there was a very interesting trend noted between PDGFR alpha positive and negative tumors that received olaratumab. There was a six month difference in overall survival noted between these populations favoring PDGFR negative tumors. So these analyses are still exploratory. And it is uncertain to the prognostic versus predictive significance of these tumors. But it's just a very interesting trend where when we're using a very selective PDGFR alpha inhibitor. Let me just follow up on that last point, Bill, which seems like a particularly important one. And it's not necessarily intuitive that the biomarker negative population seems to do better. Is it possible that PDGFR alpha is not the actual target for this drug and maybe there's a different target? We're pretty certain of the specificity of this inhibitor towards PDGFR alpha signaling, because it's a very pure monoclonal antibody. I would wonder more if there is something within mesenchymal biology regarding PDGFR signaling that we may not understand. For example, could targeting PDGFR alpha in tumors that express PDGFR alpha allow for potential up regulation of other aspects of PDGFR signaling or potentially even other signaling pathways? So one of the difficulties with soft tissue sarcoma is because it's such a heterogeneous disease, again, we may be seeing disparate biology. And because these tumors really fall into mesenchymal malignancies, we still have so much to learn about oncogenesis along mesenchymal cell lineages, and then the interplay with the tumor microenvironment and even the development of metastasis where often PDGFR or other mesenchymal signals really play a role. So where do we go from here? This drug was approved under the FDA accelerated approval pathway, as you said. That requires that post market confirmatory studies be done. The phase three trial didn't confirm the clinical benefit. And now, the sponsor has announced plans to remove the drug from the market. So first of all, what about patients who have been receiving the drug and are benefiting from it? Will they still be able to receive the drug? So fortunately, they will. As you mentioned, withdrawal is in progress. And that's important for patients and providers to know. And to me, this is the practice changing aspect of this abstract, because olaratumab did gain widespread use in almost over 40 countries. Because of these data and because we have not yet found any specific reason to explain the data, we are not recommending the initiation of olaratumab with doxorubicin in new patients with soft tissue sarcoma. But as you can imagine, many patients have been on this drug for a long period of time. And many patients and clinicians do believe that the patient is benefiting from the drugs. So this really does require informed conversations with the patient specifically regarding the data of now, and then making the decision if the patient should continue or would like to continue on that drug. And if that's the case, there is a patient access program for continuing patients. There's actually a toll free number, which is 1-833-245-8167, to gain more information about the continued use of the drug as the drug is actually withdrawn from the market. Great. That's really good to know. I'm curious to know what you think this whole experience says about the FDA accelerated approval pathway. Do you think that perhaps this drug was approved too soon? Well, I think it's a tough question for me to answer, because I'm somewhat biased, very much so regarding the unmet medical need in soft tissue sarcoma. This was the first drug that was technically approved in the upfront setting in soft tissue sarcoma for over 40 years. Normally in sarcoma, we tend to determine efficacy based on few month benefit in progression free survival. So actually having a phase two trial where we saw such tremendous improvements in overall survival for this patient population, in my mind, I think it was very important to give patients access to this drug. The other caveat to this is when we looked at the safety data between doxorubicin and placebo versus doxorubicin and olaratumab, there was very little, if any, difference regarding that safety profile. So olaratumab added very little downside to doxorubicin. So these data and the accelerated approval was really highly debated within the community. But the drug did gain widespread usage and acceptance. It wasn't unconditional. But many people really started to use the drug. I think the debate was really fueled by a smaller phase two signal, a lack of understanding potentially of the mechanisms of action, which could explain the results that we saw and also the cost, understanding that there was a significant cost with giving this drug to patients. However, being that we did not have any added toxicity, had the phase three study been positive, I would definitely have liked to allow patients in the two to three year period while we were waiting for the data of the ANNOUNCE study to have access to a potentially life improving drug as opposed to saying, we may have missed a window of a few years to get patients access to this drug. So I think the process, understanding the caveat of the data of the phase two study that I mentioned, could have really worked. The appropriate phase three study had been designed and was actually completed before FDA approval or accelerated approval was granted. So it was just a matter of waiting for that data. But I do think this is a really important topic to talk about within our community. And I also do think we should consider potentially some ways to mitigate cost for the community while we're waiting for the confirmatory results of the study to mature. So what else do you see on the horizon for treatment of patients with soft tissue sarcoma? It's clear that there's a high unmet medical need. It's a rare group of patients. As you mentioned, it's a very heterogeneous group of diagnoses and may be difficult to determine the best treatment for this heterogeneous group. Maybe patients need to be sorted. But of course, that's going to make it more challenging to recruit even smaller populations into clinical trials. But as someone who's an expert in the field, where is the field going at this point? There is a lot of hope. And I think it is still an amazing fertile ground for advancements not only in science, but also in drug development. Sarcomas really represent a major route of oncogenesis in cancer that we know very little about. We know so much more about the hematopoietic malignancies and also about the epithelioid malignancies, but very little about mesenchymal malignancies. And I think what we're seeing is a tremendous growth in our understanding of these tumors, how mesenchymal malignancies interact with tumor microenvironment and metastases. And as you mentioned, we are really beginning to also to genetically dissect out the different sarcoma subtypes. And this is yielding to some very nice advances in very specific sarcoma subtypes. So I do think as we move forward, we'll continue to see some amazing advances in single sarcoma subtypes. Examples could be diseases like tenosynovial giant cell tumors, PEComas, what we've seen in gastrointestinal stromal tumors, so a lot of hope. I do think the community is really beginning to look at these data from this and other clinical trials to say, how can we better run larger clinical trials maybe in soft tissue sarcoma in general? And is that really the right way? So there is still a tremendous amount of hope to develop drugs for patients. And really finding that right application in the right patient population is going to be critical moving forward. Bill, thanks so much. Again, today, my guest has been Dr. William Tap of Memorial Sloan Kettering Cancer Center. Thank you for being on our podcast today. Thank you so much. To our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcasts. Thank you.

Welcome to the ASCO Daily News Podcast. I'm Dr. Richard Schilsky, senior vice president and chief medical officer of ASCO. I am pleased to be joined by Dr. Christopher Sweeney, a medical oncologist and professor of medicine at Harvard Medical School and Dana Farber Cancer Institute. He presented abstract LBA2 entitled overall survival results of a phase three randomized trial of standard of care therapy with or without enzalutamide for metastatic hormone sensitive prostate cancer, the ENZAMET trial, an ANZUP led international cooperative group trial. Dr. Sweeney, welcome to the podcast. Thank you for having me. So testosterone suppression and androgen receptor blockade, of course, have been the cornerstone of treatment for men with advanced prostate cancer for many, many years. This large trial of men with metastatic hormone sensitive prostate cancer demonstrated an overall survival advantage by substituting enzalutamide for older androgen receptor blockers. Tell us more about how the patients did on this treatment. Well, the first big line item to report is that men who got the drug enzalutamide, which, as you point out, is the more potent version of the way to block the androgen receptor than our old drugs, lived longer. In terms of relative risk, men had a 33% chance of being alive longer than men who got the older drugs. In terms of absolute numbers, 80% of men who got the early drug were alive at three years versus 72%. What's buried in all those numbers, though, is that there are different patient populations. Patients who have a higher burden disease, have a faster progression, and, unfortunately, a shorter survival than men who have a lower burden of disease. With our previous iteration of this type of a trial in men starting hormones, we showed that docetaxel benefited patients who had high volume disease very clearly. And we could also see enzalutamide works just as well with docetaxel in that patient group. On the other hand, men who had a low burden of disease, we didn't really see a benefit with chemotherapy docetaxel. But we did see a big benefit here in this study with using the hormone enzalutamide. So that now comes to the question, well, what about men who are treated with docetaxel? Did enzalutamide help them? And we actually had a group of patients in this study who we can pull out and analyze separately. And we can see that the enzalutamide delayed the time to progression when it was added to the docetaxel. But at this early analysis, we don't see any meaningful impact in survival. And that could well be because men who get the hormones and the docetaxel and then have the drugs, like enzalutamide, do just as well as getting all three drugs upfront, testosterone suppression, docetaxel, and the enzalutamide, do just as well as getting docetaxel, testosterone suppression, followed by enzalutamide. So it's a little bit of a parsing out of who the patients were and what treatments they get to work out how they actually fared. Tell us a little bit more about enzalutamide. This is a drug that's already FDA approved. It's already in use for later lines of therapy. How does it differ from the earlier group of androgen receptor blockers? Do you attribute all of the benefits seen in the enzalutamide group to the drug itself, or were there differences in patient populations perhaps from groups studied with the earlier generation of androgen receptor blockers? It seems like a pretty substantial improvement just by swapping out a newer version of an old drug. Yes, that's a very interesting observation. So the first notion is that the drug was tailored and designed by chemistry to be a much more potent version of the old drugs. So they're able to see the crystal structure of the androgen receptor and then do chemistry to say, how can we block that and shut that receptor down more efficiently? What is unique about the trial design, because we ran this as an academic study, is that we incorporated in a control arm, every patient had to have one of the older less potent drugs as a control to really show that the more potent drug did actually have all the benefits and conferred the benefits over the older drug. So it wasn't versus a non-active placebo. So it's very clear as a direct more potent versus less potent drug, we had a survival benefit. The other thing to note is that we had clues that this may work is because patients who have testosterone suppression and when their cancer progressed, they had an up regulation of the androgen receptor. So the cells say, help me, help me. I need more testosterone or testosterone like hormones to live. And it up regulates that receptor to survive. And it becomes a target that we can use. Whereas the older drugs would be able to bind to it. But sometimes, they actually became agonists. They turned the receptor on rather than turning it off. Where this drug has complete antagonistic turning the receptor off properties. So it's really quite a clear more potent drug versus less potent drug leading to the survival benefit across both patients with a poor risk, higher volume disease and a lower risk, lower volume disease. It's really interesting how understanding the structure of the androgen receptor and the chemistry of the drug really seems to have led to a very substantial improvement in patient outcomes. So this is a drug, as I mentioned earlier, that's already FDA approved, although in another line of therapy, but could potentially be substituted into routine clinical care immediately. Do you think the study results justify making that switch? It's a very important question. So another way to phrase what you just said there, Rich, is we're seeing advances in advanced stage disease. And my mantra is let's go forward by moving backwards into the earliest stage disease where the patients are starting the hormone not when they're progressing on the testosterone suppression. So when they're starting the hormones, we actually see a survival benefit when we give it upfront. That is a new indication. And so it will be up to the developer of the drug, which is both co-developed by a company called Pfizer and [INAUDIBLE], to present that to the FDA and see if it will get a label extension from the castration setting, resistance setting to the hormone sensitive setting. So that's a work in progress. Now the important item is to recognize that to be able to access the drug, there's going to have to think through the side effect profile. And there are some side effects with regard to it can cause a little bit more fatigue, a little bit more impairing concentration because of the way it works. And some patients can feel a little bit more frail. So some patients have these side effects, and there have to be dose modifications. So the risk and benefit profile has to be adjudicated. But by patients living longer and having their cancer controlled for longer, most patients do get a benefit. But the flip side is we also have to work out other alternatives. Docetaxel is an alternative for patients with high volume disease. Abiraterone is another drug that's approved in this setting, which is another different type of a hormone. And when we write for these drugs, we have to adjudicate how much the patient is going to have to pay. Some patients, they have a copay of $5. Other patients, a copay of about $2,500, because these drugs are very expensive. And if patients have no insurance, the cost is close to $9,000. So I think it is a very good option that will emerge. I suspect it will get approved. But when patients are counseled by their physicians on the options, they have to review the side effects, the benefits, as well as the financial access issues. Yeah, very important points to bring up. So it always comes down to risks, benefits, and costs, and how that translates into access. So just to wrap up, obviously, prostate cancer is a very common disease. As our population continues to age, I think we can foresee that it may become even more common in the population. What's on the horizon for prostate cancer research and treatment? This is a disease where there's been a considerable amount of progress has been made in recent years. But perhaps, there's going to be a growing medical need as the population continues to age. So where do you see the future in prostate cancer research? So the first thrust of work that I'm actively involved in and have engaged with collaborations around the globe to do more trials is to go even further back into the disease setting and augment the adjuvant therapy around the time of prostate radiation or prostate surgery to decrease the risk of relapse. So we have less patients who actually develop metastatic disease and die of the disease. So a lot of us are now getting very proactive in that setting. The other setting is profiling the tumors to work out which patients would be better treated with our current chemotherapy, be it the hormones, be it the combination, as well as develop new drugs that target new targets that are identified. So early identification and more aggressive proactive treatment to prevent relapses. And if patients do relapse, interrogate the tumors more to get more informative data on how best to treat the patient with which new drugs that emerge. So just along those lines actually, your comment prompted a thought. One of the other abstracts presented in the plenary session was about a PARP inhibitor for maintenance therapy in patients with pancreatic cancer, certainly a difficult disease to treat. There's been some preliminary evidence that PARP inhibitors may have activity in prostate cancer as well. Do you think that's going to be an emerging molecular target in prostate cancer? I definitely think it will be. And to some degree, it already is a player. What we need to do is being conducted are the proper rigorous trials to work out, which is the genomic profile that of the DNA damage repaired defects in the genes like the BRCA2 gene you're referring to, that actually do portend a potential response. So we see that the DNA damage genes, response genes that may portend a response to a PARP inhibitor are about 20%. But maybe half of those are truly the genes that really are the responders, that define the responders. And the question now is, of those particular genes that are refined, how many of those actually respond and how long? So we're seeing, I would say, responses of about 50% in that subgroup. So it is very much the notion of precision medicine, because it's the precise group of patients, which inherently is a small subset, but a subset that we can identify and potentially give a meaningful treatment with a reasonable side effect profile. So that data should emerge over the next 12 to 24 months, I think, based on the status of the trials. Great. Thanks so much for giving us that little glimpse into the future. So again, today, my guest has been Dr. Christopher Sweeney from Harvard Medical School and Dana Farber Cancer Institute. Chris, thanks so much for being on the podcast today.   It was my honor. And to our listeners, thank you for tuning into the ASCO Daily News Podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcasts

Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA1 with Dr. Amy Davidoff. Welcome to the ASCO Daily News podcast. I'm Dr. Richard Schilsky, Senior Vice President and Chief Medical Officer of ASCO. I'm pleased to be joined by Dr. Amy Davidoff, Senior Research Scientist in the Department of Health Policy and Management at the Yale School of Public Health and a member of the Yale Cancer Center to discuss racial disparities in cancer care. Dr. Davidoff presented abstract LBA1 entitled "Affordable Care Act-- Medicaid Expansion Impact on Racial Disparities in Time to Cancer Treatment" during today's plenary session. Dr. Davidoff, welcome to the podcast. Thank you for inviting me. So, obviously, the Affordable Care Act has changed the landscape for patients with cancer in many ways, including by expanding insurance coverage and improving access to care. Why did your team decide to examine the impact of the ACA through the lens of racial disparities? Prior to the ACA, low income, non-elderly adults had high rates of insurance and poor access to care, whether overall or for adults diagnosed with cancer. The population of uninsured adults was disproportionately African-American and numerous studies on the effects of the Affordable Care have demonstrated increases insurance and reduced race disparities in coverage. So we decided that we really wanted to understand whether this reduction in race disparities in coverage translated into improvements in care processes. With respect to cancer, studies by policy researchers, including myself, have demonstrated increases in insurance coverage for newly diagnosed cancer patients and some evidence of earlier stage at diagnosis for newly diagnosed cancer patients but very little research related to the Affordable Care Act in cancer patients has focused on the real processes of care. The flatiron data set allows a really rich examination of that dimension. And so we decided to examine whether there were disparities in timely treatments and whether the ACA was associated with reductions in those disparities. Makes good sense. Obviously, racial disparities in cancer care pose a serious issue and, in fact, a crisis for many patients who are at risk for either a delay in diagnosis or a delay in initiation of treatment as you point out. So tell us about your findings. How has the Medicaid expansion under the ACA improved access to care for African-American patients? Why do those patients seem to have benefited more from the Medicaid expansion than the white patients in your study population? As we all know, insurance is a really important factor in improving access to health care, generally-- specifically specialty care, such as oncology care-- and particularly for very low income adults who lack the financial needs to pay for care out of pocket. So to the extent that the ACA Medicaid expansions increased insurance coverage for African-Americans, we would expect reduced delays in diagnostic, workup, treatment initiation, continuation, and improvements in other outcome dimensions. We think that African-Americans likely benefited more than others because they had the most to gain in terms of insurance coverage. So what was the actual magnitude of benefit that you observed on your time point of time to treatment initiation? Prior to the Medicaid expansion, we measured that 43.5% of African-American patients were treated within 30 days of diagnosis and that was almost 5 percentage points less than for white patients after accounting for patient age, sex, and other factors that may have affected that timing. Patients diagnosed after their state had expanded Medicaid, among those almost 50% of African-American patients were treated within 30 days, which is now less than 1 percentage point less than for white patients. So the gap between African-American and white patients that we observed prior to Medicaid expansion had almost nearly disappeared for patients who were diagnosed in states with Medicaid expansions. So as you point out your study focused primarily on time to treatment initiation and we presume that will eventually lead to better outcomes for cancer patients. Will you be continuing to study this cohort determine if better outcomes actually were observed? We certainly can do that, particularly over time as we have longer periods in which to observe patients. We have not yet looked at that. And we certainly could for patients diagnosed in states with earlier expansions. Do you attribute the findings of your research to be due entirely to Medicaid expansion and the presumed greater access to care? Or are there other potential covariates that, perhaps, you haven't accounted for that might explain the earlier time to treatment initiation? This is something I've actually been wondering about myself is, is this strictly a result of Medicaid expansion? Or could there have been other things going on in those states at the same time or with those populations at the same time that contributed to the earlier time to treatment initiation? [? We ?] think there are a lot of things that are happening during this time period, including the introduction of many of the novel immunotherapies at end of life often that require some type of genetic testing prior to deciding about treatment. And those are happening concurrent with this sort of expanding Medicaid period that we're looking at. I think, though, that we account for those changes that are occurring over time by including control variables for quarter times, the calendar quarter. We also take into account state effects which control for sort of any unchanging underlying characteristics of each state in the analysis. So in terms of covariates, I think I'm less worried about that and more interested in other ways that the Affordable Care might have influenced timely treatment. Improving access to primary care which may have somehow assisted patients to be more informed, educated about their cancer treatment options if they had a primary care provider who is assisting them in managing those transitions. If patients were being enrolled in a clinical trial, the Affordable Care Act improves access to insurance coverage for routine care for patients in a clinical trial. So there are other aspects of the Affordable Care Act that could have facilitated these changes in timely treatment. Your point about access to primary care I find really interesting. Because in a sense, it's generally the primary care physician who makes the diagnosis of cancer. It's not the oncologist. And so when you're looking at a data set of oncologists medical records, you're looking at a population of patients who have already found their way to the oncologist. But in order to get to the oncologist, they presumably enter the health care system with a primary care provider who establishes the cancer diagnosis, gets them to the oncologist who can then initiate the treatment, which was your primary outcome measure. So there is an interesting progression here from how and when the patient can actually enter the health care system when some potential cancer related symptom initially surfaces. So it's really interesting point. I try to think holistically. In terms of this policy, I think-- not to get into politics here, but I think people who see the Affordable Care Act as just insurance coverage need to sort of step back and think about the just wide range of ways that it affects health care providers, payments, health care delivery innovation, et cetera. It's really very broad. Yes, so I was going to sort of wrap up with that question. Not to get into politics, but, obviously, the Affordable Care Act has been under threat really from the moment it was passed, maybe even before that of course from those who opposed its passage. But it is at least for the moment the law of the land. I suppose it's possible that if significant changes are made over time that states will find it more difficult to sustain this Medicaid expansion. Now, just curious as to what you're thinking about over the longer term in terms of how these benefits that are accruing to these patient populations can be sustained or what the consequences could be if the Medicaid expansion can't be continued? I think it's always hard to know how people [AUDIO OUT] when you take away something new that you've given them. So it is possible that even if some of the Medicaid expansions are rescinded that people may be motivated to obtain insurance through other mechanisms, certainly people who were eligible for Medicaid under sort of the pre-Affordable Care Act mechanisms who sort of came out of the woodwork to enroll once the Affordable Care Act was publicized and promoted. Those people probably will stay enrolled in Medicaid. But for certain populations, they were never eligible previously. And so they would probably lose their coverage. And we would go back to probably newly enhanced disparities in treatment associated with insurance, which is disproportionately affecting vulnerable populations such as African-Americans. So it's certainly something that we'll have to be alert to. And, obviously, I think your research findings in a sense illustrate the potential favorable impact of Medicaid expansion, but also expose the risks of potentially retrenching from that position. So thanks a lot for discussing your research with me. It's been really a great conversation. Again, today, my guest has been Dr. Amy Davidoff of the Yale Cancer Center. Thanks for being on our podcast. You're very welcome. And to our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple podcast.

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