Podcasts

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.

In the latest ASCO in Action podcast, ASCO CEO Dr. Clifford A. Hudis shares a quick preview of what's to come for the 2020 ASCO Advocacy Summit and Week of Action, which will take place September 14-18.

Typically, ASCO volunteers from across the country gather in Washington, D.C. to advocate for policies that will improve access to high-quality, equitable care for people with cancer and ensure robust funding for cancer research through in-person meetings with their Members of Congress. Due to the COVID-19 pandemic, the 2020 ASCO Advocacy Summit will be a virtual event, but participants can expect the same important advocacy and education opportunities that the event provides every year. All ASCO members are encouraged to participate in the Congressional Week of Action by signing up with the ACT Network (through the Advocacy Center on ASCO.org).

Subscribe to the ASCO in Action podcast through iTunes and Google Play.

 

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.

Dr. Clifford Hudis: Welcome to the ASCO in Action Podcast, brought to you by the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at “Podcast dot ASCO dot org” (podcast.asco.org)

The ASCO in Action Podcast is ASCO’s podcast series that explores the policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for—people with cancer.

I’m Dr. Clifford Hudis, CEO of ASCO and the host of the ASCO in Action podcast series. For this podcast, I wanted to share with listeners a preview of the 2020 ASCO Advocacy Summit and Week of Action taking place September 14-18.

Typically, ASCO gathers volunteer advocates in Washington, D.C., in September for education sessions and in-person meetings with their Members of Congress.

Due to the COVID-19 pandemic—like so many events scheduled to take place this year—the 2020 ASCO Advocacy Summit will be a virtual event, but that said, participants can expect the same advocacy and education opportunities that the event provides every year.

ASCO volunteers will meet with Members of Congress and their staff by phone or video to advocate for policies that will improve access to high-quality, equitable care for people with cancer and ensure robust funding for cancer research.

Advocacy Summit attendees will also attend webinars to receive education and training on lobbying Congress and the current political landscape.

What is different this year is our online Week of Action, which will give all ASCO members an opportunity to advocate on critical issues of great importance to the cancer care delivery system in the United States.

Participants in the Week of Action will amplify the Advocacy Summit’s messages through email and social media messages to Members of Congress using ASCO’s ACT Network. And, it’s easy to get involved and make your voice heard. You just need to click on the link to the ACT Network in the Advocacy Center on ASCO.org and sign up to receive ASCO ACT Network emails. Then, you’ll get all the information on the fastest and easiest ways to contact lawmakers delivered directly to your inbox. We hope you will participate as much as you can—the effort will take just minutes. Even one message a day by every ASCO member to your representatives in Congress will have a tremendous impact.

During the virtual Advocacy Summit, which will be held in the middle of the Week of Action on September 16, ASCO volunteer advocates will have their virtual meetings with Members of Congress and their staff. The three issues or “legislative asks” that they will be discussing will be the same asks that ASCO members will contact their Members of Congress about during the Week of Action.

One, we will ask Congress to support legislation—The CLINICAL TREATMENT Act, which will give all Medicaid beneficiaries coverage of routine costs when enrolled in clinical trials—coverage Medicare and private insurance plans already provide. The importance of improving health equity has become even more apparent during the COVID-19 pandemic, and this legislation takes us one step closer to that goal.

Two, ASCO volunteer advocates will request lawmakers to co-sponsor the Safe Step Act, which will help protect patients from harmful step therapy protocols, which ASCO believes is never appropriate in the treatment of cancer.

And three, we’ll address the impact COVID-19 has had on cancer practices and research. Specifically, advocates will ask Congress to endorse maintaining reimbursement flexibilities for telehealth, as many oncology practices have rapidly transitioned to telehealth to ensure patients continued receiving treatment during the pandemic.  We’ll also be asking Congress to provide emergency funding to the National Institutes of Health to mitigate disruptions caused to labs and clinical trials by COVID-19, and to restart research across the county.

These are the same issues that participants in the Week of Action will be advocating for all week long in their outreach to Congress.

The goals of the Advocacy Summit and Week of Action are to advance priority legislation, amplify the collective voice of the cancer care community on Capitol Hill, and to get ASCO members involved in advocacy initiatives.

Members of Congress and their staff have grown accustomed to virtual constituent meetings, and personal stories continue to be the most effective form of advocacy, so the Advocacy Summit and Week of Action—even virtually—remain critical to ASCO’s larger advocacy efforts.

In addition to the meetings and messages between advocates and lawmakers, the ASCO Advocate of the Year and the Congressional Champion for Cancer Care will be named during the Advocacy Summit.

In closing today, I encourage everyone listening today to follow the Advocacy Summit through social media by way of the hashtag ASCO Advocacy Summit (#ASCOAdvocacySummit) on Twitter AND to participate in the Week of Action through the ACT Network.

A link to the ACT Network and all the information you’ll need to participate in the Week of Action is available at ASCO dot org slash ASCO Action (www.asco.org/ascoaction).

Until next time, thank you for listening to this ASCO in Action podcast and if you enjoyed what you heard today, don’t forget to give us a rating or review on Apple Podcasts or wherever you listen and while you are 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 dot ASCO dot org” (podcast.asco.org).

ASCO President Lori J. Pierce, MD, FASTRO, FASCO, joins ASCO CEO Dr. Clifford A. Hudis in the latest ASCO in Action podcast to discuss how her childhood inspired her to become an oncologist and how the theme of her presidential year, “Equity: Every Patient. Every Day. Everywhere.” is more important than ever as the country responds to a healthcare pandemic that is disproportionately impacting people of color.

“Every patient, no matter who they are, deserves high-quality care and every patient has the right to equitable care,” says Dr. Pierce. “We have to get to the root causes to understand the barriers that patients face if we’re going to really make a difference, so it’s important to me that equity be front and center of everything that we do."

Subscribe to the ASCO in Action podcast through iTunes and Google Play.

 

American Society of Clinical Oncology (ASCO) CEO Dr. Clifford A. Hudis is joined by Dr. Piyush Srivastava, the past chair of ASCO’s Clinical Practice Committee, in the newest ASCO in Action Podcast to discuss the recently released ASCO Special Report: A Guide to Cancer Care Delivery During the COVID-19 Pandemic. Dr. Srivastava was instrumental in developing the report, which provides detailed guidance to oncology practices on the immediate and short-term steps that should be taken to protect the safety of patients and healthcare staff before resuming more routine care operations during the COVID-19 public health crisis.

Subscribe to the ASCO in Action podcast through iTunes and Google Play.

 

Dr. John Gordan discusses the newest evidence-based guideline update from ASCO on systemic therapy for advanced hepatocellular carcinoma (HCC). He shares the updated recommendations for first-, second-, and third-line therapy for patients with Child-Pugh Class A liver disease, guidance for patients with Child-Pugh Class B liver disease. Dr. Gordan also touches on the importance of this guideline for both clinicians and patients and the outstanding questions regarding treatment options for HCC.

Read the full guideline, “Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update” at www.asco.org/gastrointestinal-cancer-guidelines.

TRANSCRIPT

This guideline, clinical tools, and resources are available at http://www.asco.org/gastrointestinal-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.02745  

Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. 

My name is Brittany Harvey, and today I'm interviewing Dr. John Gordon from the University of California, San Francisco, lead author on "Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update." Thank you for being here, Dr. Gordon.

Dr. John Gordon: Of course, happy to be here.

Brittany Harvey: Before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Gordon, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  

So, to jump into the content of this episode, first, Dr. Gordon, what prompted this update to the Systemic Therapy for Advanced Hepatocellular Carcinoma Guideline, which was last published in 2020? 

Dr. John Gordon: So, both the initial guideline in 2020 and then the update now were driven by advances in the standard of care. The original 2020 guideline was actually held for a little bit so that we could incorporate the availability of atezolizumab plus bevacizumab, which just reported back and then received FDA approval during 2020. We were happy to be able to provide what was a very timely update to clinicians about being able to use that new regimen that had really changed the face of therapeutics for advanced HCC. The update was driven again by a shift in therapeutics, specifically it was the presence of much more evidence for the use of combination CTLA-4, PD-1 or PD-L1 immunotherapy strategies. The primary thing was the availability of durvalumab plus tremelimumab, which was studied in the so-called HIMALAYA phase III trial. The key shift in this guideline was being able to incorporate those data as a second first-line option. Furthermore, when the 2020 guideline was released, data were just becoming available about the combination of ipilimumab and nivolumab, and were not covered in any great detail. So we wanted to be able to be sure to incorporate both of those regimens, which we thought were quite significant in the current therapy for advanced HCC.

Brittany Harvey: Appreciate you providing that background on the evidence informing both the original guideline and this update. Next, I'd like to review the key recommendations of this update. So, starting with, what is recommended for first-line therapy?

Dr. John Gordon: The current recommendation in the first-line setting is to offer patients either atezolizumab plus bevacizumab, sometimes called atezo-bev or durvalumab plus tremelimumab. But, at this time, those two regimens we’re not able to distinguish between them based on the primary evidence available. But there are a few distinctions in the studies and the patients that physicians may wish to consider. In particular, because atezo plus bev contains an immune therapy and then an anti vascular agent, for patients who are not eligible for antivascular agents or for whom an antivascular therapy might be of higher risk, for example, people with a history of esophageal varices or people with peripheral arterial disease, we would encourage physicians to preferentially consider durva plus treme. 

Similarly, for patients where reactivation of an autoimmune disorder is a particular concern, staying away from the more potent immune combination is also advised. But again, the data themselves support the consideration of both, and it's really up to the provider, their multidisciplinary team, and then communication with the patient to determine what is optimal for that patient.  

In addition, in the frontline setting, it is advised that for those patients who are unable to receive atezo plus bev or durva plus treme, sorafenib and lenvatinib, the traditional tyrosine kinase inhibitors that were more commonly used prior to 2020, may also be considered in the frontline setting. Furthermore, for some patients, it's also reasonable to consider the use of durvalumab alone, which is the PD-L1 inhibitor component of the durva-treme combination. 

Brittany Harvey: Understood. It’s helpful to understand which regimens are optimal for which patient population and options that are available for shared decision making between patients and their clinicians. 

So then, following those recommendations for first-line treatment, what is recommended for second-line therapy?

Dr. John Gordon: One of the things I want to be clear about the second-line recommendations is that these are largely driven by expert opinion rather than primary research studying the use of these agents after either atezo plus bev or durva plus treme. So, if you look at the history of HCC drug development, five or ten years ago, when we were confined to the use of sorafenib in the frontline setting, many studies explicitly studied the second and later-line population. But in the current era, where new frontline therapies have supplanted those agents, it becomes a little bit harder to provide a truly evidence-based answer. As a result, the recommendation is, frankly, to consider all of the options of FDA-approved agents and just as was the case of the frontline setting, to balance what might be patient-specific characteristics, both in terms of comorbidities and also ability to adhere with these regimens, which are not the easiest. All of those things should be considered when opting for a second-line agent. 

Just to be slightly more explicit about it, for those patients who've received frontline atezo-bev, the considerations would be either transitioning to a tyrosine kinase inhibitor, most classically sorafenib, lenvatinib, or cabozantinib, or in principle, ramucirumab, the biologic antivascular agent, or a CTLA-4 and PD-1 or PD-L1 combination, such as durva-treme or nivolumab plus ipilimumab. Conversely, for those patients who might have received durva-treme in the frontline setting, it's reasonable to consider either a TKI or atezo plus bev.

Brittany Harvey: Absolutely. Thank you for reviewing both those recommendations and the level of evidence behind those. I think it's important that even in areas where the expert panel didn't have a lot of evidence to go off of, there are still recommendations available for clinicians that are based on expert opinion. 

So then, following those second-line therapy options that you just described, what recommendations did the expert panel make for third-line therapy?

Dr. John Gordon: So, regarding the recommendation for third-line therapy, one of the things that we did want to make clear as a panel is that third-line therapy is a reasonable consideration in a subset of HCC patients. Quite often, five or ten years ago, it was very seldom that a patient might be considered for frontline therapy because of the burden of toxicity and/or disease progression during the first two lines. But now, for patients with intact liver function and good performance status, I think it's very reasonable to consider the same list of agents that might have been considered for second line.

And again, I think the general guidance here is if you've already given your patient both atezo-bev and some kind of CTLA-4 and PD-1 combination, it's probably best to use a non-overlapping regimen, something like a TKI. If, in the frontline setting, you followed atezo-bev by TKI or durva-treme by TKI, then it would be reasonable to look at the immune therapy combination that the patient hadn't received yet. Unfortunately, again, at this point, this is all at the level of expert guidance and personal experience. But just thinking about the mechanistic rationale behind these different combinations, and which ones your patient has had the opportunity to benefit from yet, is probably the best guidance that we can give as you move into the later line.

Brittany Harvey: Definitely. Thank you for reviewing that guidance as well. 

So then, these recommendations that you've already described refer to patients with Child-Pugh Class A liver disease. What is recommended in the guideline for patients with Child-Pugh Class B advanced hepatocellular carcinoma?

Dr. John Gordon: Thanks. I think that's another important question, and it's a part of the field that's still evolving. So this is in some ways similar to the situation for third line therapy. The level one evidence that we have and the clinical trials that were done were almost exclusively done in the context of Child-Pugh A liver function. But we know well that many patients with hepatocellular carcinoma have some degree of impairment to their liver function, making them Child-Pugh Class B or beyond. Similar to third line therapy, we do believe that it's appropriate to cautiously consider systemic therapy for these patients, particularly a better compensated patient with Child-Pugh Class B liver function may be considered. The same systemic therapy options that are considered for patients with Child-Pugh Class A may be considered here, even to the level of considering atezo-bev or durva plus treme. I will also acknowledge, though, that when considering the liver function, bleeding risk, portal hypertension, and all of the other issues that may be at play, it may end up being safer for clinicians to consider monotherapy with an agent like durvalumab or using a TKI, by simple virtue of the fact that if complications ensue, treatment can be interrupted and the therapeutic will leave the patient's system relatively promptly. The key take home here is please do consider systemic therapy in this population, but also consider it with caution, with an understanding that the underlying hepatic dysfunction also plays a role in considering and affecting the outcome.

Brittany Harvey: Thank you for reviewing those recommendations for patients with Child-Pugh Class B advanced HCC and all of these recommendations, which are based off of expert review of the evidence and consensus of the entire expert panel. 

So then, Dr. Gordon, in your view, what is the importance of this guideline update, and how will it impact both clinicians and patients with hepatocellular carcinoma?

Dr. John Gordon: I think the impact of this guideline update was really to open the field and really just make clear that the use of CTLA 4-containing combinations was appropriate for patients with HCC because those data were not available at the time of the last guideline and to try to provide some insight about where and when to incorporate them. We really think that these agents have the potential to significantly impact outcomes for patients with HCC, and so we wanted to be clear that these can be considered therapeutically even after frontline use of a PD-L1 inhibitor like atezolizumab. And so I think the key objective of this guideline is really to be enabling and really to make it clear that within the now somewhat surprisingly broad range of approved agents that we have for HCC, these options are on the table and may be used in succession, depending on patient-specific tolerance and their clinical course. 

Brittany Harvey: Absolutely. So then you've specifically mentioned that both the original guideline and the guideline update were developed to provide timely guidance from recently published randomized clinical trials. So what are the outstanding questions still regarding treatment options for advanced hepatocellular carcinoma? 

Dr. John Gordon: I think those questions are really reflected in one of the things which is challenging about these guidelines, which is that it's a very kind of open set of guidelines. We provide clinicians with a range of options, but we're really not in a position to provide much evidence-based guidance around treatment selection beyond the sort of careful avoidance of contraindications. I think that there will continue to be drug development for HCC. I think there are more potent immune therapies that are currently in use for other tumors that are being studied here, and I think we do hope to see new agents in future guidelines as well. But I really feel like the key question is going to be starting to stratify patients for who's going to be most likely to benefit from exposure to an antivascular agent, who's going to be more likely to benefit from exposure to a more potent immunotherapy so that we can give our patients the best medicine for them in the first setting, and that we're less in the position of having to sample the available options to see which one might work for our patient. And I think that's going to require significant effort, particularly, honestly, in academic medicine, as these medicines start to get used, to develop the kinds of data that will enable identification of biomarkers and mechanisms of response, as well as identification of efficacy, which has been this sort of key limiting step in HCC therapeutics for the last 10 years. Now that we've got so many effective agents, we would like to see them be more effective, but nevertheless, it's been huge strides forward. Then the question is, who gets what when? 

I think the other place of interesting development right now is the integration of locoregional therapies like embolization procedures, either chemoembolization or radioembolization, as well as stereotactic body radiotherapy with systemic therapy. My suspicion is that it's going to take a little bit more time before the use of these is really well understood and how they might fit into the current standards of care. But we're starting to see some large studies tackling this question. I think that we will see impact of the combinations of systemic therapy and local regional therapy in guidelines to come in parallel to a better understanding of which treatment is right for which patient.

Brittany Harvey: We'll look forward to all of the future developments in the care of patients with advanced hepatocellular carcinoma, and look forward to inclusion of all of the things that you just mentioned into guidelines in the future. 

So I want to thank you, Dr. Gordon, for all of your work that you've done to update these guidelines and for taking the time to speak with me today. 

Dr. John Gordon: Absolutely. And I actually just want to express what a great experience I've had working with the ASCO Guidelines team. I think that this is very challenging work, and I really appreciate the professionalism and commitment that they bring to it. I think it has a huge impact, and I'm glad to be part of it.

Brittany Harvey: Absolutely.

And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

The purpose of this podcast is to educate and inform. It 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, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

 

 

Dr. Lisa Law and Dr. Randy Taplitz share the latest evidence-based recommendations from ASCO on vaccines in adults with cancer. They discuss recommended routine preventative vaccinations, additional vaccinations and revaccinations for adults undergoing HSCT, CD19 CAR-T treatment, or B cell-depleting therapy, guidance for adults with cancer traveling outside the U.S., and recommendations for vaccination of household and close contacts of adults with cancer. Dr. Law and Dr. Taplitz also share their insights on the guideline, including the importance of this guideline for adults with cancer and their clinicians, future advances in research, and current unmet needs. Read the full guideline, “Vaccination of Adults with Cancer: ASCO Guideline” at www.asco.org/supportive-care-guidelines.

TRANSCRIPT

This guideline, clinical tools, and resources are available at http://www.asco.org/supportive-care-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00032      

The ASCO Specialty Societies Advancing Adult Immunization (SSAAI) Project is supported by the Centers for Disease Control and Prevention (CDC) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award to the Council of Medical Specialty Societies (CMSS) (with 100 percent funded by CDC/HHS). The contents are those of the authors and do not necessarily represent the official views of nor endorsement, by CDC/HHS or the U.S. Government.

Brittany Harvey: Hello, and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. 

My name is Brittany Harvey, and today, I am interviewing Dr. Lisa Law from Kaiser Permanente and Dr. Randy Taplitz from City of Hope Comprehensive Cancer Center, authors on “Vaccination of Adults with Cancer: ASCO Guideline.”

Thank you for being here, Dr. Law and Dr. Taplitz.

Dr. Lisa Law: Thank you.

Dr. Taplitz: Thank you, Brittany.

Brittany Harvey: Before we discuss this guideline, I'd like to take note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Taplitz and Dr. Law, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. 

So then, to dive into the content, here first, Dr. Taplitz, can you provide a general overview of both the scope and purpose of this guideline on vaccination of adults with cancer?

Dr. Randy Taplitz: Yes, so people with cancer often experience a compromised immune system due to a variety of factors. This includes chronic inflammation, impaired or decreased function of the hematopoietic system, and treatments that compromise their immune function. Because of this, people with cancer are at a higher risk for infection, including with vaccine-preventable diseases. Also, response to vaccines in patients with cancer may well be affected by this underlying immune status, and their anticancer therapy, as well as the severity of the underlying malignancy. The purpose of vaccination in this group of patients is to prevent infection or to attenuate the severity of the disease when infection cannot be fully prevented.  

This ASCO review builds on a 2013 guideline by the Infectious Diseases Society of America, or IDSA, and uses what’s called a systematic literature review of 102 publications between 2013 and 2023. This includes 24 systematic reviews, 14 randomized clinical trials, and 64 non-randomized studies. The largest body of evidence in these studies, not surprisingly, addresses COVID vaccines on the efficacy and safety of vaccines used by adults with cancer or their household contacts. ASCO convened an expert panel to review this evidence and formulate recommendations for vaccinations in this population.

Brittany Harvey: Understood. I appreciate that context, Dr. Taplitz. So then, next, Dr. Law, I'd like to review the key recommendations of this guideline. The guideline addresses four overarching clinical questions. So starting with the first question, what are the recommended routine preventative vaccinations for adults with cancer?

Dr. Lisa Law: Thank you, Brittany. Before I start, I just want to wholeheartedly thank the first author of this paper, Dr. Mini Kamboj, Dr. Elise Kohn from the NCI, as well as the ASCO staff in putting this publication and guideline together. It is a very, very important guideline, and I echo everything Dr. Taplitz just said. 

So going back to your question, what are the recommended routine preventative vaccines for adults with cancer? As per this guideline, there are about 7 to 8 based on patient age and risk. Namely, they are: seasonal flu, RSV for those aged 60 or above, COVID-19, Tdap, Hepatitis B, Shingrix, Pneumococcal vaccine, and the HPV vaccine. These vaccines should ideally be given two to four weeks before therapy. However, non-live vaccines can be given anytime during or after chemo, immunotherapy, hormonal treatment, radiation, or surgery.

Brittany Harvey: Excellent. Thank you for reviewing those vaccinations and the timing of them as well. So then, following those recommendations, Dr. Taplitz, what additional vaccinations and revaccinations are recommended for adults undergoing hematopoietic stem cell transplantation, CD19 CAR-T treatment, or B-cell depleting therapy? 

Dr. Randy Taplitz: Many studies have shown that stem cell transplant recipients essentially lose immunity from childhood immunizations, and we know that these individuals are very vulnerable to infection, particularly in the first year after transplant. Revaccination is critical to help restore their immunity. The optimal timing of vaccination is based on our understanding of adequate immune reconstitution with B and T-cell recovery so that the individual can mount a response to the vaccine. We know that a lot of factors influence this immune reconstitution, including the age of the stem cell transplant recipient, the source of the donor, the time from transplant, graft-versus-host disease prophylaxis, the treatment and severity of graft-versus-host disease, and the vaccine type and antigens used.  

There are a number of bodies throughout the world, IDSA as I mentioned, CDC, American Society for Transplant and Cellular Therapy, European Society for Blood and Marrow Transplant, and European Conference for Infections and Leukemia. All of these bodies have guidelines that approach vaccination in stem cell transplants. However, variation does exist in the use of a variety of things including whether to use immune predictors to help guide vaccination, and there is really not consensus on whether this immune predictor guided vaccination is more likely to produce a protective immune response versus a standardized schedule. In addition, the duration of protection is incompletely understood. 

The bottom line in these guidelines is that they recommend complete revaccination starting for most vaccines at 6 to 12 months after stem cell transplant, in order to restore vaccine-induced immunity. And I just want to go through a few of the particulars. For COVID-19, which is a three-dose series in the primary series, influenza - generally high-dose influenza - and pneumococcal vaccine, PCV20 in general, ultimately four doses, can be administered, starting as early as three months after transplant. Although there is really not much data to guide the use of the recombinant zoster vaccine in allogeneic stem cell transplant, the vaccine can be administered after the end of antiviral prophylaxis, which in general is 12 to 18 months after allogeneic and 3 to 12 months after autologous stem cell transplant. Some of the other vaccines, such as hepatitis B, Tdap, meningococcal vaccines, and HPV revaccination in those less than 45 are also recommended.  

I want to also spend the moment talking about the two recently licensed RSV vaccines, which were essentially studied in less compromised hosts and really without any immunogenicity data in stem cell transplant, and thus, there is no recommendation in this guideline for the use of these vaccines after transplant. Live vaccines, such as MMR and varicella – varicella would be in varicella-seronegative patients without a prior history of varicella – should be delayed for at least two years and only given in the absence of active graft-versus-host disease or immunosuppression. 

Moving briefly to CAR T, which is an immunotherapy that involves adoptive cell therapy, given the available data and after a review by the group, it was recommended that adults with hematopoietic malignancies receiving CAR T therapy directed against B-cell antigens should receive influenza and COVID-19 vaccines either two weeks before lymphodepletion or no sooner than three months after the completion of therapy. Administration of non-live vaccines preferably should occur before CAR T treatment or at least 6 to 12 months after, following the same timing as what we recommend for stem cell transplant. There is really little data to guide the safety and timing of administration of live vaccines after CAR T therapy.  

In terms of adults receiving B-cell depleting therapy, they are generally unable for time to mount an effective humoral response but may have at least partially intact cellular immune responses. They are encouraged to be revaccinated for COVID-19 no sooner than six months after completion of B-cell depleting therapy, and they should receive influenza vaccine approximately four weeks from the most recent treatment dose for patients on chronic therapy. For other non-seasonal immunizations, vaccines ideally should be given two to four weeks before commencing anti-CD20 therapy or delayed until 6 to 12 months after completion, except for the recombinant zoster vaccine, which can be given one month after the most recent dose of B-cell depleting therapy.

Brittany Harvey: I appreciate you reviewing each of those vaccinations and when they should be given, and reviewing the available data – albeit, limited data – in these situations. 

So beyond these routine preventative vaccinations and revaccinations that you've both just described, Dr. Law, what additional vaccinations does the expert panel recommend for adults with cancer traveling outside the United States?

Dr. Lisa Law: Good question. As per these ASCO guidelines, adults with solid or blood cancer traveling outside of the United States should follow the CDC standard recommendations for their destination. For the 2024 CDC Yellow Book, travel vaccines, in general, should be delayed until three months from the last chemotherapy or, and for those with solid tumors, ideally when the disease is in remission. Of note, hepatitis A, typhoid, inactivated polio, Hep B, rabies, meningococcal vaccine, and Japanese encephalitis vaccines are considered to be safe. In all cases of travel, patients should be counseled by their healthcare provider about the travel timing, with the additional attention to the regional seasonality of infections, for instance, influenza is more common in late summer in Australia, and also with attention to any outbreaks that may be occurring globally at the time of travel.

Brittany Harvey: Absolutely. Those are key points for clinicians to discuss with their patients as they consider upcoming travel. 

So then, the final clinical question that the panel addressed, Dr. Taplitz, what vaccinations does the panel recommend for household and close contacts of adults with cancer? 

Dr. Randy Taplitz: Thank you. Yes, it is recommended that all household members and close contacts, when possible, be up to date on their vaccinations. And the only further thing I would say is that there are some special considerations for the use of live vaccines in household contacts, particularly in stem cell transplant recipients. Contacts of people who receive stem cell transplants should preferably receive inactivated influenza vaccines. As was mentioned, MMR and varicella vaccines are both safe to administer to close contacts. Vaccine strain transmission to immunocompromised hosts has not been associated with MMR use in family members.  

Eleven cases of the varicella vaccine strain transmission are described in the published literature, but none occurred in compromised hosts. Because the vaccine strain can cause severe and fatal varicella in profoundly immunocompromised people, precautions are advised to avoid close contact with a person with a vaccine-induced rash. For household contact travelers, MMR and yellow fever vaccines are considered safe. Oral cholera should be avoided. For smallpox vaccines, the second-generation ACAM2000 has rarely been associated with vaccinia transmission and should be avoided because of this. But the live replication-deficient MVA-based JYNNEOS vaccine is felt to be safe for household contacts of immunocompromised individuals.

Brittany Harvey: I appreciate you reviewing the importance of vaccination for household and close contacts, and some of those precautions that individuals should take. I appreciate you both for reviewing all of these recommendations. 

So then in your view, Dr. Law, what is the importance of this guideline, and how will it impact both clinicians and adults with cancer?

Dr. Lisa Law: In my opinion, this is a very important guideline that is long overdue in the oncology community and will have a huge impact on both clinicians and adults with cancer. Over the years, I have often been asked by my colleagues and patients, “Can I have the flu vaccine, and if so, when?” So this guideline really is going to be helpful. More importantly, our cancer patients are living much longer. They may have years of quality of life even with third or fourth line of treatment, especially, for instance, like CAR T for myeloma and lymphoma. However, we know that with additional treatment, that carries a substantial risk of infection complication among these immunocompromised patients. So it is of paramount importance to inform our patients and colleagues to be proactive in advocating preventive therapy ahead of time, meaning trying to get the patients appropriately vaccinated as early as possible to generate immunity. 

Another case in point is the Shingrix vaccine. I used to see lots of shingles, but ever since we have the recombinant Shingrix, I have fewer encounters. And this is huge because post-herpetic neuralgia robs a patient’s quality of life. So, again, it is very important to recommend appropriate vaccines for our cancer patients. 

Brittany Harvey: Absolutely. It is key to ensure patients receive these preventative vaccines, and we hope that this guideline puts an emphasis on that for clinicians and patients. 

So finally, to wrap us up, Dr. Taplitz, what are the current gaps in knowledge regarding the vaccination of people with cancer?

Dr. Randy Taplitz: There are a number of really important gaps in knowledge and really critical unmet needs that require research and other dedicated efforts. Among these are, and I think paramount, are really the participation of people with cancer with varied types of immunocompromise in vaccine trials. Where vaccine trials are only for cancer patients, obviously is ideal, testing vaccines in the appropriate population. But when that's not feasible, pre-existing cancer should not preclude eligibility, and inclusion of cohorts of people receiving anticancer treatment should be incorporated prospectively. So that’s really critical because the quality of our guidelines is based upon the data. We use the data for developing guidelines and gathering more data in the particular patient population is really, really critical. 

Secondly, work for creating more immunogenic vaccines and research to understand the immune response to vaccines after immuno-depleting therapies, particularly with newer therapies such as CAR T and newer B cell therapies, bispecific antibodies, etc. is really critical. We need to really understand the immune response and have the most potent vaccines available to these people who may have impaired immune responses. 

Switching gears a little bit, we really need mechanisms to promote institutional commitment to integrate and sustain immunization best practices for people with cancer. This will largely be through multidisciplinary, team-based approaches, protocol-based vaccination standing orders, and leveraging data sharing so that we can all be on the same page with giving vaccines to these individuals. We also need education and evidence-based decision-making tools, emphasizing preventive care through immunization, the availability of educational resources to clinicians and patients to address commonly asked questions and also misconceptions about vaccination, that’s absolutely critical. 

And finally, I think we need to develop strategies for addressing unique challenges and factors contributing to vaccine hesitancy during cancer therapy. We need to focus on patient and clinician communication, and very importantly, we need to consider health equity considerations in the development and approach to vaccines in these compromised patients.

Brittany Harvey: Definitely, we'll look forward to research and advances in these areas that you've just described to support these guidelines and increase vaccine uptake. 

So I want to thank you both so much for your work on this important guideline, and thank you for your time today, Dr. Law and Dr. Taplitz.

Dr. Lisa Law: Thank you. 

Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

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. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

 

 

 

Dr. Ilana Braun and Dr. Eric Roeland join us on the ASCO Guidelines podcast to discuss the latest evidence-based recommendations on cannabis and cannabinoids in adults with cancer. They discuss nonjudgmental patient-clinician communication, the relatively narrow cancer-related indications for which there is actionable clinical evidence for cannabis and/or cannabinoids, and key information for adults with cancer and their clinicians. Dr. Braun and Dr. Roeland also review the limited evidence regarding cannabis and cannabinoid use in adults with cancer and the outstanding questions and importance of research in this area.
Read the full guideline, “Cannabis and Cannabinoids in Adults with Cancer: ASCO Guideline” at www.asco.org/supportive-care-guidelines.

TRANSCRIPT

This guideline, clinical tools, and resources are available at http://www.asco.org/supportive-care-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, 

Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcast hosts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all of the shows, including this one, at asco.org/podcasts. 

My name is Brittany Harvey, and today, I’m interviewing Dr. Ilana Braun from Dana-Farber Cancer Institute, and Dr. Eric Roeland from Oregon Health & Science University, co-chairs on “Cannabis and Cannabinoids in Adults with Cancer: ASCO Guideline.”  

Thank you both for being here Dr. Braun and Dr. Roeland.

Dr. Ilana Braun: Thanks so much for having us, Brittany.

Dr. Eric Roeland: Thanks, Brittany.

Brittany Harvey: Then, just before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensures that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Braun and Dr. Roeland, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.

Then to jump into the content of this guideline, first, Dr. Roeland, could you give us an overview of both the scope and purpose of this guideline? 

Dr. Eric Roeland: Sure, Brittany. I think it's important for everyone to recognize just how common the issue of cannabis or cannabinoid use is amongst people living with cancer. And I think clinicians in academia as well as through community sites, we are asked about the use of cannabis on a daily basis. And so our target audience is really to focus on clinicians providing care to adults with cancer, but also the health systems in which we work because this is a very complex issue, as well as the people living with cancer and their caregivers, as well as researchers dedicated to this field.

Brittany Harvey: So as you mentioned, this is a complex issue, and I'd like to review the key recommendations of this guideline. This guideline provides recommendations across three clinical questions that the expert panel targeted. So, starting with the first question, what is recommended for patient-clinician communication regarding cannabis or cannabinoids? 

Dr. Ilana Braun: Given the high prevalence of medicating with cannabis or cannabinoids that Eric references, somewhere in the neighborhood of 20% to over 40% of adults with cancer consume cannabis products, ASCO's guideline offers the following common-sense, good practice statement: In the clinic, providers should routinely and non-judgmentally inquire about cannabis consumption or consideration of cannabis, and either guide care or direct adults with cancer to appropriate resources. In other words, the guideline works to fully destigmatize this conversation. The guideline goes on to offer suggestions for taking a cannabinoid and cannabis history. This includes the goals of use, how the products are sourced, what formulations are being used (including the ratios of active ingredients like THC and CBD), the inactive ingredients (for instance coconut oil), whether it is herbal or synthetic, and whether the product is pharmaceutical grade or non-pharmaceutical grade. And then other questions like routes of administration, dosing schedules, perceived benefits and risks, and whether the products are being used adjunctively or as a replacement for standard treatments. It is also probably important to query potential contraindications, such as a history of cannabis use disorder or psychosis. 

Brittany Harvey: Thank you for reviewing those good practice statements. Those are key for non-judgmental communication and taking an accurate and complete history. 

So following those statements, the expert panel next addressed the question: Does use of cannabis and/or cannabinoids by adults improve cancer-directed treatment? What recommendations did the expert panel provide for this section?

Dr. Eric Roeland: When we think about the use of cannabis or cannabinoids in treating the underlying cancer, it's incredibly important to recognize the excitement that patients and clinicians have around the potential promise. Much of this data is generated from preclinical models. However, when we're engaging patients consuming cannabis or cannabinoids to augment their cancer-directed treatment, we could find no evidence to support its use. And so we do not recommend that patients be using it to augment treatment, nor do we recommend that patients should be using it instead of their cancer-directed therapy. And I think this is a major challenge for multiple oncologists, where their patients may be using these with a goal of treating their cancer, and then present with very advanced cancer and/or multiple poorly controlled symptoms.

Dr. Ilana Braun: And I think that there are some areas of particular concern. For instance, there were two oncologic cohort studies that suggest that cannabis, which we know is an immune modulator, may actually worsen immunotherapy outcomes. These outcomes included median time to progression and overall survival. There are obvious limitations of preliminary observational data, and we now need to gather prospective, gold-standard data. But for the time being, the guideline recommends that clinicians should advise against adults receiving immunotherapy from medicating or considering medicating with cannabis and cannabinoids. And then I think there are some additional reasons for concern. First of all, this type of therapy tends to be very expensive and not covered by insurance and there are some risks for drug-drug interactions, in terms of pharmacodynamic ones, Cannabis may exacerbate neuropsychiatric side effects of opioids and even benzodiazepines. In terms of pharmacokinetic drug-drug interactions, it's not a particularly risky substance, but there are three to be wary of in particular: warfarin, buprenorphine, and tacrolimus all have high-risk interactions with cannabinoid products. 

Brittany Harvey: I appreciate you both for reviewing these recommendations and evidence regarding the use of cannabis and/or cannabinoids regarding cancer-directed treatment.  

So then the last clinical question, Dr. Braun, what is recommended regarding use of cannabis and/or cannabinoids in managing cancer treatment-related toxicities and/or symptoms?

Dr. Ilana Braun: The first thing to make clear is that high-quality clinical evidence evaluating the utility of cannabis and cannabinoids for adults with cancer is limited as Eric has said. The evidence that does exist weakly supports a practice of using cannabis and cannabinoids to address refractory chemotherapy-induced nausea and vomiting when standard treatments have failed. For other potential oncologic indications, like management of cancer-related pain, there is weak, negative, conflicting, or no evidence. But that being said, a 2017 monograph published by the National Academies of Science, Engineering, and Medicine concluded that there is substantial evidence that cannabis is an effective treatment for chronic non-cancer pain, and I’m sad to say, that chronic non-cancer pain happens too in adults with cancer.

Brittany Harvey: Thank you for reviewing those recommendations as well. 

So you've both touched on this a little bit in that patients are often asking clinicians for recommendations regarding cannabis and/or cannabinoids, but in your view, what is the importance of this guideline, and what should clinicians know as they discuss these recommendations with their patients?

Dr. Eric Roeland: Probably one of the most important points is for clinicians to ask and to be open and to create a space where our patients are telling us about what they're using. I think we've all had patients that we’ve been surprised that have been using cannabis or cannabinoids in conjunction with other medications that may increase the risk of unwanted side effects or risks, including sedation or falls. I also find it challenging that many patients are receiving recommendations for the use of cannabis or cannabinoids directly from friends or family instead of through their medical providers. Therefore, I think one of the very first things is to just make sure that you’re asking about it and then inquiring what the goal of their use is. 

When we talk about the use of cannabis, we also need to recognize the difference between the available data that can guide us in evidence-based recommendations, as well as the enthusiasm and available access that patients have to cannabis that has really outpaced our ability to research it. So it's important to recognize these tensions that we're living with in clinic day-to-day.

Brittany Harvey: Absolutely. Those points are key for clinicians as they discuss this complex issue with their patients. 

Following that, how will these guideline recommendations affect adults with cancer?

Dr. Ilana Braun: One really important takeaway from these guidelines is that they clearly state that cannabis and cannabinoids are medicinal, and for a medical community to clearly articulate this point is notable. I suspect they will provide encouragement, legitimacy, confidence, and even a script to oncology clinicians who were previously reticent to inquire, document, and provide clinical recommendations around non-pharmaceutical cannabis and cannabinoids. It may have a similar effect even at the institutional level in terms of supporting these practices. At the same time, I suspect they will encourage those who are recommending oncologic use of cannabinoids and cannabis for myriad cancer-related indications to adopt a more circumscribed approach. The reason I say this is that the cancer-related indications for which there is actionable clinical evidence at this time are quite narrow. So all this to say, I believe these guidelines will lead to greater transparency around cannabis decision-making in the clinic, as Eric mentions, but also lead to a possible narrowing of indications for which cannabis is clinically recommended. 

Dr. Eric Roeland: Another major role of the use of these guidelines in clinical care is informing clinicians and patients about cannabis. Cannabis has been used by humans as a plant for thousands of years, and although it's a very complex plant with hundreds of parts, the two parts that researchers have studied most are delta nine-tetrahydrocannabinol, or THC, and cannabidiol, or CBD. In rough terms, THC can cause a high feeling, while CBD typically does not. And there are multiple types of products that have different ratios of THC and CBD. So it's critical for people to understand what those ratios are, how many milligrams of those things there are, as well as what are the programs within your region to measure or quantify what's actually in the products you're consuming.

If a person with cancer medicates with cannabis, most oncologists would prefer that they use it by mouth, such as an edible, rather than inhaling or smoking cannabis given concerns about potential impact on lung function. One challenge when consuming cannabis by mouth is that it can take up to two hours to have its full effect. So patients should be very careful not to take too much or to stack their doses, which can cause sedation, confusion, and even increase the risk of falls. Whereas when patients are consuming cannabis by breathing in a smoke or vapor, they typically feel the effects almost right away, which is why patients sometimes prefer smoking or vaping as their preferred route of administration.

Brittany Harvey: Understood. Definitely. We hope these guidelines provide key information and clarity for both adults with cancer and their clinicians. 

So then, finally, you've both mentioned that there is limited evidence regarding cannabis and cannabinoid use in adults with cancer. So what are some of the outstanding questions regarding cannabis and cannabinoids in cancer care?

Dr. Eric Roeland: Thanks, Brittany. I think the questions also align with priorities for future research, and we need to recognize that the lack of evidence aligns with some of the challenges of funding research in this space. However, ongoing future research priorities include what is the nature of healthcare disparities pertaining to medical cannabis use by adults with cancer, and what are effective means to address these disparities? We also wonder, what are the optimal strategies to maximize communication in the oncology clinic regarding medical cannabis and/or cannabinoid use? And when we're thinking about cannabis and/or cannabinoids for cancer treatment specifically, we still need to know do cannabis and/or cannabinoids possess clinically meaningful anticancer activity in humans. We also need to understand what are the drug-drug interactions with our standard-of-care cancer treatments, including cytotoxic chemotherapy, targeted therapy, immunotherapy, radiation, and combinations of all the above. We also are wondering what the effect of cannabis and/or cannabinoids on outcomes in adults with cancer receiving some of our newer therapies, including antibody-drug conjugates and some of our newer vaccine therapies. 

Dr. Ilana Braun: I might add that collating the existing research as the guideline did is a very good first step and should serve to highlight where the gaps in knowledge lie. This guideline discusses some of the unique challenges to conducting cannabis and cannabinoid research, including limitations in funding source and study drug, red tape procedures, and issues around legalization. I believe it will take a group of highly determined and creative researchers to move the needle forward in this area, but we must.

Brittany Harvey: Definitely. Thank you both so much for all of your work developing this guideline and creating these evidence-based recommendations. And thank you for taking the time to come on the podcast today and teach us all a little bit more about cannabis and cannabinoids in cancer care. And thank you for your time, Dr. Braun and Dr. Roeland.  

Dr. Ilana Braun: Thanks so much, Brittany.

Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

The purpose of this podcast is to educate and 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. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

 

Dr. Angela DeMichele, Dr. Lynn Henry, and Dr. Harold Burstein present the latest breast cancer rapid recommendation update impacting two ASCO guidelines. This update focuses on the new option, capivasertib plus fulvestrant, for patients with hormone receptor-positive, HER2-negative metastatic breast cancer with activating PIK3CA or AKT1 mutations or inactivating alterations in PTEN based on data from the recent CAPItello-291 trial. They discuss the updated recommendations on lines of endocrine treatment and selecting between the options for patients with activating PIK3CA mutations. Additionally, we discuss implications for clinicians and patients, and what ongoing research is occurring in the field.

Read the latest update, “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer – Capivasertib-Fulvestrant: ASCO Rapid Guideline Update“ at www.asco.org/breast-cancer-guidelines.

TRANSCRIPT

This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00248

Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.  

My name is Brittany Harvey, and today I am interviewing Dr. Harold Burstein from Dana-Farber Cancer Institute, Dr. Angela DeMichele from the University of Pennsylvania, and Dr. Lynn Henry from the University of Michigan, co-chairs on “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Capivasertib–Fulvestrant: ASCO Rapid Guideline Update.” Thank you for being here, Dr. Burstein, Dr. DeMichele, and Dr. Henry.

Dr. Harold Burstein: We're happy to be here. 

Brittany Harvey: And before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including our guests on this episode today, are available online with the publication of the guideline update in the Journal of Clinical Oncology, which is linked in the show notes. 

So then, to kick us off, Dr. Burstein, could you first describe what prompted this rapid update, which provides updated recommendations for two ASCO guidelines: the biomarkers for systemic therapy in metastatic breast cancer guideline, and the endocrine treatment and targeted therapy for hormone receptor-positive, HER2-negative metastatic breast cancer guideline?

Dr. Harold Burstein: Thanks, Brittany. Well, this team has been working, as you mentioned, actually, on two guidelines, which are clearly evolving in parallel and kind of converging, actually, when you look at data, as we'll be talking about in the next few minutes. The particular catalyst here was a large randomized clinical trial which looked at a new targeted therapy in the space of estrogen receptor-positive, HER2-negative breast cancer. That drug is capivasertib. And the trial was the so-called CAPItello study. In that trial, patients who were receiving second-line therapy with fulvestrant were randomized to that treatment alone, or that plus capivasertib. So the data from that study were the first strong signal that we needed to update the guideline because they were important clinical data.  

The other strong signal was that the drug was tested in a cohort of patients who had a specific set of mutations in their cancers. And that included PIK3CA mutations, a class of mutations for which we already had a targeted drug. But it also included some new potential targets, including mutations in the AKT gene itself, capivasertib is an AKT inhibitor, as well as loss of PTEN protein functionality, which potentially sensitizes tumors to the targeted action of this drug as well. So while we had a couple of guidelines catching up on the endocrine therapy space, which is increasingly looking like a targeted therapy space, it was clear that this major study, which had clinical and diagnostic implications, would sort of push them together and served as the impetus for updating both guidelines at the same time.

Brittany Harvey: Understood. I appreciate that background information.  

So then, Dr. DeMichele, based on this updated data that Dr. Burstein just described, what is the updated recommendation from the guideline panel regarding lines of endocrine treatment?

Dr. Angela DeMichele: Well, I think this is where the biomarker evolution that Dr. Burstein just referred to really comes in because now we have the opportunity to perform genomic testing in patients who have ER-positive, HER2-negative metastatic breast cancer, on either the tumor or commonly from the blood. And we can now start to tailor treatment to the specific genomic abnormalities that that patient's tumor contains. So now our guideline really marries both the genomic abnormality with the therapeutic option. First-line treatment remains endocrine therapy plus a CDK 4/6 inhibitor. But things then really start to diverge once we enter second and third-line therapy because at that point, we now have the option to test for several genomic markers: ESR1 mutations, PIK3CA mutations, AKT1 mutations, and PTEN inactivation. And based on whether the tumor has one or any of those mutations, we can then select the therapy based on that. 

So in the case of capivasertib, as you just heard, that is a therapy for patients whose tumors have PIK3CA mutations or activating mutations in AKT1 or loss of PTEN. But other patients who don't have one of those mutations may, in the second line, go on to another drug. For example, if they have an ESR1 mutation, they then may be eligible to take elacestrant. Patients who have no targetable mutations still have a targeted option in that they can use everolimus. And in all of these settings, the endocrine therapy partner for this line of therapy is typically fulvestrant. So now we're really starting to tailor therapy in the second- and third-line based on genomic changes.

Brittany Harvey: Excellent. That information is helpful for choosing optimal therapy tailored to the individual patients, as you just described. 

So then, Dr. Henry, what guidance does the expert panel provide regarding choosing a PIK3CA targeted option?

Dr. Lynn Henry: Thank you. So for patients whose tumors are found to have an activating mutation in PIK3CA, we now have two drug options: either alpelisib or capivasertib in combination with fulvestrant. And the problem is, these drugs have not been compared head-to-head. We can't say that one is clearly better than the other, either in terms of efficacy or in terms of side effect profile. What we do have is information from two separate trials in which they were each tested against placebo. The efficacy appears to be fairly similar based on the data that we have. It does appear that the side effect profiles may be slightly different. And so, when you have a patient sitting in front of you and you're trying to decide how best to treat her, you really have to think about, what symptoms does my patient already have? What is she more or less likely to tolerate? So what we do know is that it appears that the rates of grade 3 diarrhea and rash were slightly higher with capivasertib. It looks like hyperglycemia was higher with alpelisib, as was treatment discontinuation. So really you have to make an individualized decision when you have a patient sitting in front of you about which drug you'd like to try. Of course, if someone doesn't tolerate one drug, you can always switch to the other one. 

Brittany Harvey: I appreciate that analysis and to provide guidance without a head-to-head trial and to specifically provide options based on an individual patient's profile.  

So then, Dr. DeMichele, what should clinicians know as they implement these new recommendations? 

Dr. Angela DeMichele: Well, first of all, I think most clinicians now are becoming more familiar with the procedures required for doing genomic testing. But this is something that now has become the standard of care. And so, it is incumbent upon all of us who treat these patients to understand what the options for genomic testing are for that patient, which companies offer this testing, how to send a sample, and how to interpret the report that comes back. So, I think this has really added a level of complexity to the therapy for patients. I also think that one can’t simply apply an algorithm to a patient. We have to really treat the whole patient and we have to take into consideration, as Dr. Henry said, the toxicities of these agents and the cost which is also a major issue. So I think that while it is more complex, really that doctor-patient relationship is so important in communicating what these genomic tests mean for a patient and for their options, and also important for the clinician to really understand what the different therapeutic agents might mean for a patient, and really try to pick the agent that’s best for that patient. Using genomic testing is just one of several different features that they’ll consider.

Brittany Harvey: Absolutely. It’s key to obtain the data needed to select appropriate patients and to recognize the complexity.  

So then, Dr. Henry, in your view, how will this update impact patients with metastatic breast cancer?

Dr. Lynn Henry: Yes, so as we’ve discussed, I think this is really exciting. Over the last few years, we have had quite a number of new medications that have become available for patients and have been FDA-approved. And so this is yet the latest in a series. For those patients whose tumors have a PIK3CA mutation, as we discussed, there are now two options. So you have a choice depending on which one is better covered by insurance, by which one you may tolerate better. But I think the other thing is now, although it’s a smaller subset of patients, there are patients out there whose tumors have mutations in AKT1 or alterations in PTEN, and so there’s an entirely new endocrine therapy-based option available for them that wasn’t available before. So I think that thinking about the new data that are out there, the new drugs that are out there, really is exciting because there are new options available and hopefully there are more to come as well.   

Brittany Harvey: Absolutely. It's great to have these new options. 

So, finally, Dr. Burstein, Dr. Henry just mentioned what's to come. Could you touch on what some of the outstanding questions are regarding endocrine therapy for patients with metastatic breast cancer? 

Dr. Harold Burstein: A couple of things to say. First, ER-positive metastatic breast cancer is the most common kind of metastatic breast cancer, roughly three quarters of metastatic cases of breast cancer will be hormone receptor-positive cancers. So this is a very big public health issue around the world, actually, breast cancer being the number one most commonly diagnosed cancer of women around the world. So minor or major improvements in treatment for advanced ER-positive breast cancer really have a tremendous impact. 

The second thing is it’s been remarkable to see the progress in the past decade. We’ve gone from simply targeting the hormonal access itself with medicines like tamoxifen or aromatase inhibitors or an injectable selective estrogen receptor degrader like fulvestrant to incorporating targeted therapies at the same time. And this whole class of drugs called CDK4/6 inhibitors has emerged which we use in either first- or in second-line therapy. Those drugs have transformed our standard of care, improved survival for patients with advanced ER-positive disease, now with median survival nearly 50% longer than what we had seen in the past.  And if you’ve heard, we have a wealth of opportunities. We can target PIK3CA, we can target ESR1 mutations. Other drugs emerging in the space include PROTACs which is another way of degrading the estrogen receptor. And so there’s going to be more progress in the years to come.  

So one of the biggest challenges has been to try and understand, is there really an optimal way to use these drugs, or can we be smarter about the particular sequence of all these particular things that are happening.  So one example of this was a recent study that is on a drug, not as yet FDA-approved, called inavolisib, which is a PIK3CA targeted drug used in first line in combination with a CDK4/6 inhibitor and endocrine therapy. And that study, for a high-risk group of women with ER-positive metastatic disease, actually showed a dramatic improvement in overall survival, asking the question if combining some of these targeted therapies together might yet further improve outcomes. 

And as you’ve heard from the diagnostic space, one of the other interesting things is that tumors evolve over time. And so acquisition of the estrogen receptor mutations, ESR1 mutations, which are typically not found early in the course of advanced breast cancer but otherwise later, now have targeted treatments. So there’s a whole bunch of stuff going on all at the same time, including multiple ways of targeting things, serial testing to look for acquisition of ESR1 mutations and new pathways to explore. It’s an embarrassment of riches in some respects because it has meant it’s actually really hard to write a guideline as you’ve heard, which says, “Do this first, do this second, and do this third.” I suppose that’s a good problem to have under the circumstances, but it’s going to require really thoughtful clinical trials and careful analysis to help guide specific lines of treatment recommendations like that. 

Brittany Harvey: Excellent. We’ll look forward to these exciting, continuing developments for patients with metastatic breast cancer. And I want to thank you all so much for your work to develop this rapid recommendation update for these two guidelines. And thank you for taking the time on this podcast today.

Dr. Harold Burstein: Thanks.

Dr. Lynn Henry: Thank you so much. 

Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

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, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

 

 

 

Dr. Natash Leighl and Dr. Jyoti Patel are back on the podcast to discuss the update to the living guideline on stage IV NSCLC with driver alterations. This guideline includes recommendations for first-, second-, and subsequent-line therapy for patients with driver alterations including: EGFR, ALK, ROS1, BRAFV600E, MET exon skipping mutation, RET rearrangement, NTRK rearrangement, HER2, and KRAS G12C. They highlight the key changes to the recommendations, addition of recent trials, the importance of biomarker testing, and the impact of this guideline for clinicians and patients living with advanced NSCLC. Stay tuned for future updates to this continuously updated guideline.

Read the full update, “Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3” at www.asco.org/living-guidelines.

TRANSCRIPT

This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.02744.   

Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   

My name is Brittany Harvey, and today I am interviewing Dr. Jyoti Patel and Dr. Natasha Leighl, co-chairs on “Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3.” Thank you for being here, Dr. Patel and Dr. Leighl. 

And before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Patel and Dr. Leighl, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.

So, to start us off on this living clinical practice guideline, Dr. Leighl, this guideline for systemic therapy for patients with stage four non-small cell lung cancer with driver alterations is being routinely updated. What new data was reviewed in this full update to the living guideline?

Dr. Natasha Leighl: Thanks so much, Brittany. So, we looked through the literature for publications between February and the end of October 2023, and also any novel agents that were approved, in particular by the United States FDA, to really incorporate this update in the current guidelines. In particular, we had updates in EGFR-driven tumors, BRAF and RET-driven tumors. And we also worked very hard to make this more digestible. In particular, it was turning into a bit of a laundry list of all of the things that we had ever recommended. So we really wanted to shorten things, pare them down, and really make them helpful and very, very current for the treatment of people with lung cancer in 2023 and 2024.

Brittany Harvey: Excellent. Thank you for providing that overview of the evidence reviewed and the key updates that we will address in this guideline. So then I would like to talk about some of those key updated recommendations from the expert panel. You mentioned both EGFR, BRAF, and RET. So starting with patients with stage IV non-small cell lung cancer with EGFR alterations, Dr. Leighl, what are the key changes to those recommendations?

Dr. Natasha Leighl: So, as I said, we really started to get quite a long list of things we recommended, including drugs that, to be honest, we no longer think are what we should lead with first-line. So we updated the recommendation to recommend first-line osimertinib in patients with sensitizing mutations. We were also able to capture in this update for patients with EGFR exon 20 insertion mutant lung cancer, the data from the randomized PAPILLON trial, recommending amivantamab plus chemotherapy for progression-free survival benefit. Not yet an overall survival benefit, but we will see how these data mature. 

The other thing that we did was we moved all of the- I don't want to call them "legacy agents" because, in many countries, these are still very important. But older agents such as gefitinib, approaches such as gefitinib plus chemotherapy, and drugs like dacomitinib and other agents where we truly believe as an international panel that we would prefer a third-generation kinase inhibitor like osimertinib. We moved all of those to our discussion, just to recognize that, around the world, not everybody may have access. And we also specified that things are different in different countries. So, for example, in China, there are other third-generation kinase inhibitors with randomized data to support their use. And those are approved and used in China. And also, for example, in Korea, there are other agents that are used. So, we have really tried to be both inclusive and yet keep things simple at the same time. And hopefully, we have succeeded. 

One of the challenges was that, with all of the updates that we made, we did not have all of the publications out yet at the end of October to make recommendations about moving beyond osimertinib in the first-line setting. So, please stay tuned for the next guideline update, where we’re going to tackle whether we should give osimertinib alone or combination therapy.

Brittany Harvey: Excellent. Thank you for providing those updates and clarifications for those patients with non-small cell lung cancer and an EGFR alteration. And we will look forward to the guideline panel's review of that evidence and future updates as well.

So then, Dr. Leighl, you had previously mentioned that additional recommendations were updated, such as those for patients with BRAF alterations and RET alterations. So, Dr. Patel, what are the other key updated recommendations from the expert panel?

Dr. Jyoti Patel: Thanks so much, Brittany. So certainly, I think we have seen many of these trials mature over time, which has been fantastic. I think one remarkable achievement was the reporting of a phase III selpercatinib trial. This was a trial in the front-line setting, in which patients who were RET-positive were randomized to selpercatinib versus carboplatin-based chemotherapy. And the selpercatinib significantly outperformed platinum-based chemotherapy, and I think really demonstrated a significant improvement in progression-free survival. So, based on that phase III trial, the recommendation for selpercatinib was elevated. Many of these agents that are used in clinical practice are approved initially on smaller phase I or phase II trials. And so, seeing the maturity of these phase III trials gives clinicians and patients greater certainty that these agents are really effective. And so, the evidence was increased for that, and that's now a preferred agent over another TKI, pralsetinib, in which there is only phase II data. So, certainly, those kinds of real things that we can explain to patients are important in these guidelines. 

Another thing that we were able to update was another doublet for BRAF ^V600E non-small cell lung cancer. So, the combination of the two TKIs, encorafenib and binimetinib, was also included in the guidelines. 

One thing that we tried to help was really identifying the best therapy post-progression on these first-generation TKIs. And again, there is a paucity of data, but often we went back to carboplatin-based doublets, and there is some data regarding whether or not patients with driver alterations should get immunotherapy in the second-line setting. And so, certainly, I think we have a number of randomized studies for patients with classical EGFR mutations, and our recommendation is generally avoidance of immunotherapy for these patients and treating many of these patients with carboplatin and pemetrexed when appropriate. I do not think we have the data for a lot of other subsets of patients. So, again, stay tuned as these data evolve.

Brittany Harvey: Thank you for reviewing those updated recommendations and the supporting evidence. I think it's helpful for our listeners to understand the level of evidence behind these recommendations as well. 

So then, Dr. Leighl, what should clinicians know as they implement these new and updated recommendations?

Dr. Natasha Leighl: It's really important, first of all, to make sure that you have the information that you need to get your patients to these great new treatments as part of the shared decision-making process. So your patients need biomarker testing. You need to get that as quickly as you can. As Dr. Patel has highlighted, you really want to get that before they start their first-line therapy, if at all possible. We also really tried to bring out in this guideline that when things are delayed, I mean, this is the real world that we live in, just to be very cautious of immunotherapy with chemotherapy for that first cycle. That obviously, again, is a discussion with your patient, but this concept that the approach of a cycle of chemotherapy while you wait for the next-generation sequencing testing. And then if the patient does not have a driver alteration, adding any other therapy as appropriate is okay. It's something that people do. We believe it's important as we talk about the balance between benefits and harms. And so I think that's in there for clinicians, and I hope that they and patients can really benefit from that to avoid toxicity and also to really improve the ability to get molecular testing results first line. 

Also, I think it's really important that when people read the wording of the guidelines, that this really follows GRADE, which is a type of system that we use to develop our recommendations. And so things like "may" do not mean that you shouldn't do it. So sometimes we'll hear back from clinicians and say, "Well, you said that they may use alectinib or lorlatinib, for example, with ALK, and I can only get coverage for one or the other." And so I think it's really important that clinicians and patients recognize that all of the things that we do recommend, even if we do use the word "may" or the recommendation is more conditional, we do think that these agents should be available for patients and clinicians, and that they go through this shared decision-making process together. 

And so I think that's something that clinicians, we hope, can help take forward as they advocate for their patients to get access to these different and new and emerging treatments that have clearly shown benefit. Even when we say patients and clinicians may use this or that, there may be excellent reasons for using something newer, that’s emerged, perhaps for toxicity benefits or benefits in terms of efficacy, even though we can't compare directly. And so we really want clinicians and patients to be empowered to access these new compounds and these new exciting agents that are in our guidelines.

Brittany Harvey: Absolutely. Thank you for reviewing those key points. And, yes, that's a great comment that the level of obligation in the recommendations may be based on the evidence quality, but that doesn't mean that clinicians and patients shouldn't have access to all of the recommended treatment options to offer patients based off their individual patient and clinical characteristics. 

So then, Dr. Patel, in your view, how will these changes affect patients with non-small cell lung cancer, with driver alterations? 

Dr. Jyoti Patel: A lot of this echoes the points made by Dr. Leighl. I think there are opportunities for patients to assess toxicity or what it means for intensification of therapy. So, particularly for EGFR patients, for example, we have data that chemotherapy with osimertinib can improve progression-free survival, or the incorporation of a bispecific antibody, amivantamab, can improve progression-free survival over the TKI alone. It certainly comes with increased toxicity. And so how we weigh this in the absence of a known survival benefit at this juncture is one that, again, really gives patients the opportunity to prioritize what's important for them. And so I think this guideline affects patients and that we have multiple options, we help with the weight of the evidence so they may be able to better discern what treatment makes sense for them.

Brittany Harvey: Understood. Yes, this guideline provides lots of options for different patients based off their driver alterations. So it's helpful to have that information for shared decision-making with their clinicians. 

So then finally, to wrap us up, Dr. Leighl, what current research is the living guideline expert panel monitoring for updates to the guideline recommendations?

Dr. Natasha Leighl: This process of the living guidelines has really been to help us stay on top of the amazing and incredibly rapid progress that we're making in lung cancer and other cancers. And even with this process, where we're trying to stay up-to-the-minute, there have already been some changes in the literature between the start of November and now. And so we're already working on some additional commentary and options for the first-line treatment of patients with EGFR-mutant lung cancer. Also, the subsequent treatment of patients with EGFR-mutant lung cancer, depending on what they've had before. Also, a great new study in patients with ROS1 fusion-driven lung cancer. And so these are some of the things that we're looking at.  

Also, a bit more discussion about the importance of molecular testing. In our companion article, the Journal of Oncology Practice, along with Dr. Patel, we're going to be talking a bit more about new ways to genotype, for example, using both liquid biopsy and tumor tissue at the same time, and some of the support for that and how it gets us with our patients to the answers that they need faster. 

Brittany Harvey: Absolutely. The pace of research in non-small cell lung cancer has moved quite quickly. So we definitely appreciate the panel's efforts to review all of this evidence on a continuous basis and take the time to develop these guideline recommendations for both clinicians and patients with non-small cell lung cancer. 

So I want to thank you so much for your work to update these guidelines, and thank you for your time today, Dr. Patel and Dr. Leighl.

Dr. Natasha Leighl: Thanks so much. It's a real pleasure to be here.

Dr. Jyoti Patel: Thank you. 

Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. 

The purpose of this podcast is to educate and 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. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.