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.

 

Ms. Charité Ricker, MS, CGC and Dr. Nadine Tung, MD, FASCO share updates from the new ASCO guideline on selection of germline genetic testing panels in patients with cancer. They discuss highlights on family history collection, when and how multigene panel germline genetic testing should be used, which genes are generally recommended for testing, and how germline genetic testing interfaces with somatic genetic testing. Ms. Ricker and Dr. Tung also note the importance of the guideline and the impact of these new recommendations on clinicians and patients with cancer.

Read the full guideline, “Selection of Germline Genetic Testing Panels in Patients with Cancer: ASCO Guideline” at www.asco.org/molecular-testing-and-biomarkers-guidelines.

TRANSCRIPT

GDL 24E13

This guideline, clinical tools, and resources are available at www.asco.org/molecular-testing-and-biomarkers-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.24.00662 

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. Nadine Tung, a medical oncologist from Beth Israel Deaconess Medical Center in Boston, and Ms. Charité Ricker, a cancer genetic counselor with the Norris Comprehensive Cancer Center at the University of Southern California and Los Angeles General Medical Center, co-chairs on, “Selection of Germline Genetic Testing Panels in Patients with Cancer: ASCO Guideline.”

Thank you for being here, Ms. Ricker and Dr. Tung.

Dr. Nadine Tung: Pleasure. 

Ms. Charité Ricker: Thank you.

Brittany Harvey: Then, 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. Tung and Ms. Ricker, 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 start us off first, Dr. Tung, could you provide us a broad overview of both the purpose and scope of this guideline?

Dr. Nadine Tung: Sure. A main impetus for creating the guideline is that oncologists are increasingly being tasked with ordering genetic testing for hereditary cancer risk for their cancer patients. More and more now, they may find themselves sending the test and then seeking guidance from genetic experts to interpret the result. And these panels range from focused tests with just a few genes to comprehensive ones that include over 100 genes. So it can be very overwhelming for an oncologist to be able to understand ordering these tests and explaining them to their patients. So, we believe that it was important to offer some guidance and direction on the use of these multigene panels.

Brittany Harvey: Thank you for setting the stage for this guideline and the recommendations that come from it.  

So then, Ms. Ricker, this guideline addresses four overarching clinical questions. I'd like to review the recommendations based on each of those questions for our listeners. So starting with that first question, what is the importance of family history collection in the setting of germline multigene panel testing and which elements of family history are the most important?

Ms. Charité Ricker: Thanks. As a genetic counselor, this is probably one of my favorite questions. I love the opportunity we have to sit with families and really dig into family history. But family history collection can be overwhelming and a big lift sometimes in busy clinics where genetics is not the focus. So, what we tried to do was to break down the key elements of what components of family history are most relevant to informing which test to do, and also the interpretation of those test results. And I like to think about the key pieces of family history as being the who, what, and when of somebody's family cancer history. Who was diagnosed with cancer within their close relatives? And usually we're most focused on first and second degree relatives. So parents, siblings, grandparents, aunts, and uncles. But sometimes relevant history might go into third degree relatives like cousins or more distant. So the who being who has cancer on both sides of the family? And then the what: what kind of cancer was it? Or where did that cancer begin? And the when: how old was that individual at the time they were diagnosed? Often we ask patients maybe not to fixate on the exact age, but to give us a sense. So was this somebody who was diagnosed young, in their 20s or 30s or older, in their 60s or 70s? Because that at least gives us a ballpark around what might be relevant for understanding the genes that should be included on somebody's test. 

When we are thinking about the purpose of this history, as Dr. Tung said, often the range of multigene panels might be from a few very focused genes to a very broad panel. Family history can help us understand if we need to step beyond the very focused genes that might be relevant for the patient's history of cancer and include other genes that might be indicated based on that family history. So I think about the role that family history has at the time of identifying which test to do and then its role when interpreting what those results mean for the patient and their family. Again, Dr. Tung touched on the fact that we are often testing very large panels. However, we still don't know everything. And so a negative genetic test result does not mean that somebody does not have additional cancer risk. And family history becomes our kind of guiding star for understanding if there is still a need to change the cancer screening and prevention management for that individual and their family members.

Brittany Harvey: Absolutely. Those are key points to understanding the important role of family history for each individual patient. 

So then moving to the next clinical question, Dr. Tung, what does the panel recommend regarding when and how multigene panel germline testing should be used, when germline genetic testing is indicated?

Dr. Nadine Tung: Well, anytime multiple genes need to be tested, as Ms. Ricker said, because of the patient's own personal cancer history, or their family history of cancer and close relatives, it's appropriate to consider a multi-gene panel. And in truth, we rarely ever just order one gene these days. Perhaps we do if there's a known gene like a BRCA gene in the family, and a relative just wants to know if they have that. But it's not all that common. And to be clear, as Ms. Ricker is going to cover a bit later, we are recommending that the appropriate minimal panel at least include the genes relevant to the patient's own cancer and the cancers in their relatives. 

But it's worth thinking about what are some of the pros and cons of ordering genes beyond that, beyond the patient's own cancer or their relatives? Well, for pros, since a patient's awareness of their family history may be incomplete, testing for a larger number of cancer risk genes does ensure that significant pathogenic variants won't be overlooked. And sometimes, even if the family history is well known, pathogenic variants in important cancer risk genes can be found even when the family history would not have prompted testing for them. But it is important for clinicians to appreciate that bigger isn't necessarily better. Some larger panels may include genes for which management of pathogenic variants is not entirely clear and that can create anxiety or unnecessary screening. And if the clinician receiving the information is not well informed about the significance of the finding, that can lead to unnecessary treatment and sometimes even unnecessary surgeries.  

And I'd add one final point that clinicians must have a system for communicating reclassification of these variants, the ones with uncertain significance that we call VUS. Because as the number of genes tested increases, so does the likelihood of encountering these VUS. So I would say those are some of the main points about when to use the panel and when to think about larger or smaller panels.

Brittany Harvey: Yes, I appreciate you reviewing both the pros and cons of expanding the genes included in multi-gene panel testing and the importance of variants of uncertain significance.  

So then Dr. Tung just touched on this, but speaking of minimal panels and which genes should be included, Ms. Ricker, what are the recommendations on which genes are generally recommended for germline genetic testing?

Ms. Charité Ricker: I think this is one of the harder questions that our group took on as we were working on this guideline. I don't think there is a one size fits all and one easy answer to this question. However, we chose to approach it by selecting the more common solid tumors that oncologists see in their clinics and the ones where the role of genetic testing is most well defined, as well as some very rare tumors where they're kind of easy. So we know that all individuals with certain types of cancers, even though they are rare, should merit genetic testing regardless of age of diagnosis, family history. 

And so as we approached it, and I really appreciate ASCO’s support in helping us develop some tools and tables that hopefully will be important aids for clinicians who are trying to make these decisions, we took the approach of, as Dr. Tung mentioned, selecting kind of a minimal set of recommended genes where most individuals who are informed in this area would agree that if nothing else was done, these genes should be done, but then also acknowledged that there is an expanding understanding about the impact of certain genes on cancer risk, and so then also provided a kind of a next level if somebody wanted to be more expansive, what we would recommend less strongly, but would be reasonable to consider. Then I think the other last piece that the committee felt was important to acknowledge is that given how common, in comparison to some of these genetic conditions that we work with, pathogenic variants in BRCA1 and BRCA2 can be, and also the important clinical impact of those genes along with the genes associated with Lynch syndrome, we felt that those were important to think about in the setting of all cancer patients. So if you're approaching a panel and thinking about what genes to include, looking at that kind of minimally recommended based on the patient's personal and family history, maybe the next level, which might include some additional genes that we have included in kind of the less strongly recommended category for those tumor types. And then consideration of the BRCA1 and 2 genes and genes associated with lynch syndrome, if they weren't already encapsulated by your other personal and family history considerations.

Brittany Harvey: Definitely. This was a big lift for the panel to tackle, and the tools and tables that you mentioned are all available online with the publication in the Journal of Clinical Oncology. So listeners who are looking for more specifics on that can definitely refer to those tools and tables there. 

Dr. Tung, the last clinical question: which patient should be offered germline genetic testing, who will have or who have previously had somatic genetic testing?

Dr. Nadine Tung: Identifying which genes identified through the tumor testing should trigger germline testing is really important for assessing our patients’ future risk of cancer and their relatives. So during the development of our guidelines, the ASCO expert panel became aware that the ESMO Precision Medicine Working group had updated their recommendations for this topic, namely germline testing in response to tumor test findings. And these recommendations were based on the Memorial Sloan Kettering IMPACT registry, which consists of nearly 50,000 tumors and paired germline testing. Given the sheer volume of that data and the methods that ESMO used, our group decided to use that as a framework to develop our recommendations. The ASCO guideline provides a list of genes that, if found in the tumor, a pathogenic variant in those genes may prompt germline testing. 

And we offered or proposed two different approaches. The first approach, which is broad and perhaps simplest, involves doing germline testing if a pathogenic variant is found in any of the genes listed. But then we offer a conservative approach to test the germline for all highly actionable genes, like BRCA1 and 2, or lynch genes that are found in a tumor, but for less actionable genes, testing the germline only if the pathogenic variant is found in a tumor relevant to that gene. So, for example, ATM, if found in breast cancer or pancreatic cancer, would trigger germline testing with this approach, but not if found in lung cancer, whereas with the permissive first approach, you would simply test the germline if any pathogenic variant is found in any of the genes on the list. This latter, more conservative approach, while less sensitive for identifying every germline pathogenic variant, increases the likelihood that a pathogenic variant found in the tumor will actually be germline. That approach considers the limited resources available, such as genetic counselors, and respects trying not to overwhelm a system already stressed.

Brittany Harvey: Thank you for reviewing both of those approaches and to you both for discussing all of the recommendations included in this guideline.  

Finally, to wrap us up, in your view, Ms. Ricker, what is the importance of this guideline and how will it impact both clinicians and patients with cancer?

Ms. Charité Ricker: I hope that this guideline can open the door for more expansive and appropriate utilization of germline genetic testing. For me, I think about, from both the clinical and patient side, for example, all ovarian cancer patients have had a recommendation for germline genetic testing for many years. Nonetheless, data from multiple research studies has shown us that ovarian cancer patients still are not being tested universally, and this has important implications for their treatment plans and for their family members. And so even in the setting where genetic testing, if I can use the phrase, has been simple in that it didn't require family history, it didn't require even a specific age criteria, it was just broad, testing is not utilized as much as it should be, and then you step into the world of more complex decision making around genetic testing for other tumor types. And so we hope that this provides a framework to simplify that decision making process for providers to increase appropriate utilization.  

And then from the patient perspective, I also think about the lack of access of genetic testing in underrepresented communities and minoritized patient populations where there's many barriers that patients face in accessing genetic services. And so if we can help reduce the barriers for this piece of the genetic testing process, my hope is that that opens up better avenues for access to testing, not just for patients with certain tumor types, but for all patients from all communities and backgrounds.

Brittany Harvey: Yes, those are key points. We hope that this guideline helps all patients access the appropriate testing to better inform their cancer prevention and treatment. 

So I want to thank you both so much for your work on this comprehensive guideline on germline genetic testing and all of the work that you put into it. And thank you for your time today. Ms. Ricker and Dr. Tung, 

Dr. Nadine Tung: Thank you.

Ms. Charité Ricker: It was a pleasure to be here. 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/molecular-testing-and-biomarkers-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. Jyoti Patel discusses the latest update to the stage IV NSCLC with driver alterations living guideline, specifically for patients with EGFR or ROS1 alterations. She shares the latest recommendations based on recently published evidence, such as the FLAURA2, MARIPOSA-2, and TRIDENT-1 trials. Dr. Patel talks about how to choose between these new options and the impact for patients living with stage IV NSCLC, as well as novel drugs the panel is monitoring for future guideline updates.

Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.1” at www.asco.org/living-guidelines.

TRANSCRIPT

This guideline, clinical tools, and resources are available at 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.24.00762 

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. Jyoti Patel from Northwestern University, co-chair on, “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.1.” 

Thank you for being here today, Dr. Patel.

Dr. Jyoti Patel: Thanks so much.  

Brittany Harvey: Then, 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. Patel, 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 then to dive into the content of why we're here today, Dr. Patel, this living clinical practice guideline for systemic therapy for patients with stage four non-small cell lung cancer with driver alterations is being updated on a regular basis. So what prompted the update to the recommendations in this latest update? 

Dr. Jyoti Patel: This recent update, I think, absolutely reflects how quickly the science is changing. The landscape of treatment options for patients with advanced non-small cell lung cancer is evolving so rapidly, and guidelines from even six months ago don't address some of the newest approvals and newest data and the newest clinical scenarios that we're presented with when we see patients. I think it's harder because before there was usually a single answer, and now there are a number of scenarios, and we hope that the guideline addresses this.

Brittany Harvey: Absolutely. The panel's had a lot of data to review as you keep this guideline up to date. 

So then this latest update addresses updates to both EGFR and ROS1 alterations. So starting with EGFR, what are the updated recommendations for patients with stage four non-small cell lung cancer and an EGFR exon 19 deletion or exon 21 L858R substitution? 

Dr. Jyoti Patel: So for patients with classical driver mutations in EGFR, our recommendation remains that patients should be offered osimertinib. We now also have data to support intensification of therapy with osimertinib and chemotherapy. The FLAURA2 trial was a global randomized study in which patients with classical mutations were assigned to receive either osimertinib or osimertinib with doublet chemotherapy. The trial showed that progression free survival was longer with osimertinib plus chemotherapy with a hazard ratio that was pretty profound, 0.62. In patients who had CNS metastasis as well as patients with L858R mutations, this benefit remained and was perhaps even greater. Now the study remains immature in terms of OS. What we can say is that chemotherapy adds toxicity, so the inconvenience of 13 weekly infusions, expected toxicities from chemotherapy of myelosuppression and fatigue. I think this- we’ll continue to watch as the study matures to really see the OS benefit, but certainly intensification in the frontline setting is an option for patients. 

The other major update was for second and subsequent line therapy for these patients with EGFR mutations. Another important trial, a study called MARIPOSA-2, was published in the interim, and this was for patients who had received osimertinib in the frontline setting. Patients were randomized to one of three arms. The two arms that are most relevant for us to discuss are chemotherapy with amivantamab or chemotherapy alone. Chemotherapy with amivantamab was associated with an improvement in progression free survival with a hazard ratio of 0.48 as well as improvements in response rate with almost a doubling of response rate to the mid 60%. There was certainly an increase in AEs associated with amivantamab, primarily rash and lower extremity edema and importantly infusion reaction. Based on this data, though in the superior PFS and response rate, we've said that patients after osimertinib should be offered chemotherapy plus amivantamab. Patients may opt for chemotherapy alone because of the toxicity profile, but this recent update is reflective of that data.

Brittany Harvey: Excellent. Thank you for reviewing those updated recommendations and the supporting evidence behind those recommendations. I think that's important to the nuance and the toxicity associated with these new recommendations as well.  

So then, following those recommendations, what are the updated recommendations for patients with stage four non-small cell lung cancer and a ROS1 rearrangement?

Dr. Jyoti Patel: ROS1 fusions have been noted in a small but important subset of patients. We now reflect multiple new options for patients. Traditionally, crizotinib was the primary drug that was recommended, but we now have two very active drugs, repotrectinib, and entrectinib, that have both been FDA approved. Repotrectinib was approved based on a study called the TRIDENT-1 trial. In this study, patients who were treatment naive, who had not received a prior TKI, had a response rate of 79% and a long duration of response over 34 months. For patients who had received prior TKIs, so primarily crizotinib, the response rate was lower at 38%. But again, very clinically meaningful. Repotrectinib has known CNS activity, so it would be the favored drug over crizotinib, which doesn't have CNS penetration. The decision between entrectinib and repotrectinib is one, I think, based on toxicity. Repotrectinib can cause things like dizziness and hypotension. Entrectinib can cause weight gain, and also has CNS effects.

Brittany Harvey: Appreciate you reviewing those recommendations as well. 

So then you've already talked a little bit about this in terms of deciding between some of the options. But in your view, what should clinicians know as they implement these new recommendations, and how do these new recommendations fit into the previous recommendations?

Dr. Jyoti Patel: So there's an onslaught of new data, and certainly many of us want to remain at the front of our fields and prescribe the newest drug, our most effective drug, to all of our patients. But for the person living with cancer and in the practice of medicine, I think it's much more nuanced than that. For example, for a patient with an EGFR mutation exon deletion 19, the expectation is that osimertinib will have a deep and durable response. Certainly a patient will eventually have progression. I think the decision about intensification of therapy and chemotherapy on the onset really has to do with how much the patient is willing to deal with the inconvenience of ongoing chemotherapy, the uncertainty about what comes next after progression on chemotherapy. It may be, though, that a patient may very much fear progressive disease, and so that inconvenience is lessened because anxiety around feeling like they're doing everything for their cancer is diminished by intensification of therapy. Others who may have a large volume of disease or profoundly symptomatic, or who have L858R or brain metastasis it may make sense to give chemotherapy again, we're improving the time until progression significantly by combination therapy.

Brittany Harvey: Definitely those nuances are important as we think about which options that patients should receive, along with shared decision making as well. 

So then what do these new options mean for patients with EGFR or ROS1 alterations?

Dr. Jyoti Patel: It's fantastic for patients that there are multiple options. It's also really hard for patients that there are multiple options, because then again, we have to really clarify aims of therapy, identify what's really important in patient experience and the lived importance of treatment delivery and the burden of treatment delivery. Now more than ever, oncologists have to know what's new and exciting. But patients have to be willing to ask and participate in the shared decision making - understanding their cancer and understanding that their options are absolutely important. As patients start making their decisions, we have the data just in terms of trial outcomes. I think we're now trying to understand the burden of treatment for patients. And so that piece of communicating financial toxicity, long term cumulative lower grade toxicity is going to be more important than ever.

Brittany Harvey: Absolutely. It's great to have these new options, and those elements of communication are key to ensuring that patients meet their goals of care. 

So then finally, as this is a living guideline, what ongoing research is the panel monitoring for future updates to these recommendations for patients with stage four non-small cell lung cancer with driver alterations?

Dr. Jyoti Patel: It's certainly been an exciting time, and that's primarily because we've been able to build on years of foundational science and we have new drugs. Patients have been willing to volunteer to go on clinical trials and to think about what treatment options may be best. Now, the work really comes on seeing the longer term outcomes from these trials. So looking at these trials for overall survival, we want to also better identify which patients will benefit the most from these treatments and so that might be additional biomarker analysis. So it may be that we can identify patients that may need intensification of therapy based on tumor factors as well as patient factors as well in those patients in whom we can de-escalate treatment. I think there are a number of new compounds that are in the pipeline. So fourth generation EGFR TKIs are certainly interesting. They may be able to overcome resistance for a subset of patients who progress on osimertinib. We also think about novel drugs such as antibody drug conjugates and how they'll fit into our paradigm with osimertinib or after carboplatin-based doublets.

Brittany Harvey: Definitely. We'll look forward to both longer term readouts from the current trials and new trials in this field to look at additional options for patients. 

So I want to thank you so much for your time today, Dr. Patel, and thank you for all of your work to keep this living guideline up to date.

Dr. Jyoti Patel: Great. Thanks so much, Brittany. It really is an exciting time for people who treat lung cancer and for patients who have lung cancer. We certainly have a long way to go, but certainly the rapid uptake of these guidelines reflect the progress that's being made. 

Brittany Harvey: Absolutely. And just a final thank you to all of our listeners for tuning into 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, 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 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. Bradley Hunter, MD, MPH and Ms. Amy Evers, BSN, RN, OCN, MBA join us on the latest episode of the ASCO Guidelines Podcast to share key points and insights on the updated ASCO-ONS antineoplastic therapy administration safety standards for adult and pediatric oncology standards. They highlight key updates across the four standards domains: (1) creating a safe environment, (2) patient consent and patient education, (3) ordering, preparing, dispensing, and administering oral and parenteral antineoplastic therapies in a health care facility, organization, or in the home, and (4) monitoring during and after antineoplastic therapy is administered, including adherence, toxicity, and complications. They also comment on the importance of these standards to provide a framework for optimal safe and effective care for all patients.
Read the standards, “Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards” at www.asco.org/standards.

TRANSCRIPT

These standards, clinical tools, and resources are available at www.asco.org/standards. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the JCO Oncology Practice, https://ascopubs.org/doi/10.1200/OP.24.00216

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. Bradley Hunter from Intermountain Health and Amy Evers from the University of Pennsylvania, authors on “Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: American Society of Clinical Oncology – Oncology Nursing Society Standards.” Thank you both for being here.

Dr. Bradley Hunter: Yeah, thanks. Good to be with you.

Amy Evers: Thank you.

Brittany Harvey: Now, before we discuss these standards, I'd like to note that ASCO takes great care in the development of its guidance products and ensuring that the ASCO Conflict of Interest Policy is followed for all standards. The disclosures of potential conflicts of interest for the expert panel are available online with the publication of the standards in the JCO Oncology Practice, which is linked in the show notes. 

So then to start us off, Dr. Hunter, what prompted an update to the ASCO-ONS standards? And what is the scope of this update?

Dr. Bradley Hunter: The last guidelines were published in 2016. And just thinking about in the world of oncology, so much has changed since that time. There are a lot of therapies that have become commonplace now that were really not used too much before, including oral genomically determined targeted therapies, immunomodulatory agents, CAR T cell therapy, bispecific antibodies, etc. So there's really been a need to just talk about how do we navigate those therapies and how do we create systems of care in which they are delivered safely. Additionally, the sites of care have changed. I think all of us, eight years ago, wouldn’t have imagined a global pandemic, and how that would have changed the way that we needed to deliver oncology care. So there's been a huge influx of telehealth, including tele-oncology centers, where the oncologist and the patient may never even meet face to face, but just by video. And so it relies on a team approach for that sort of an outreach setting. Intermountain Health spans seven states, there are so many sites like this that we have and I know that we are not unique. This is an issue and a global thing now. Additionally, patients are even getting chemo in their own homes, so that has changed and we need to figure out how to address that so that everyone could be able to have that site of care so they can get there and they can get their therapy in a safe manner. 

So, these varied care settings present a challenge to us as oncology providers to ensure that a standard of quality of care is maintained, and that the therapies can be given to patients no matter where they live and that we maximize benefit while minimizing risk to the patient. So I mean, just thinking where we are now, I can't imagine where we're going to be eight years from now or the next time these guidelines are updated.

Brittany Harvey: Absolutely. Thank you for setting the stage and the impetus for this update. It sounds like a lot has changed in the last few years to impact these standards. 

So then I'd like to review the key points of the standards and the key updates for our listeners. There are four domains of standards. Starting with domain one, Amy, what are the key points of the standards for creating a safe environment for all routes of antineoplastic therapy?

Amy Evers: So domain one is all about who can write chemotherapy orders, who can prepare chemotherapy and then who can administer that chemotherapy and then what their competencies are both initial and then ongoing. So looking at the existing standards, we did end up making a few updates mainly on how providers discuss and document pregnancy status and fertility preservation with patients. And I think this is really timely given that we're seeing a big uptick in younger patients that are being diagnosed with cancers that were typically considered “old person diseases”. And I think we can and we should do better in ensuring that patients who want to preserve their ability to have a family one day can do so before they start treatment. 

The update also included the addition of an assessment for social determinants of health, calling out financial and logistical constraints that patients may face as part of their cancer journey, which I think is extremely important making sure that we have equitable access to care regardless of a patient's background, their financial status, everybody's receiving the highest quality of care they can in their community. 

And the last change that we made was to highlight an accurate measurement of height and weight using metric units, which is important when we're calculating the doses of drugs for some of these very high risk medications. 

Brittany Harvey: Excellent. Thank you for reviewing those important points for our listeners. 

So following those standards, for domain two, Dr. Hunter, what are the key standards for patient consent and patient education?

Dr. Bradley Hunter: In domain two, we’re really seeking to figure out what policies around treatment planning, patient consent and patient's education are shown to result in fewer medical errors and reduce preventable harm? But one of the big things we've found is having a really detailed understanding of exactly what a patient is taking in terms of medications, including over the counters and supplements and herbal remedies, really helps reduce medical errors. You know, some of the research and literature we came across suggest that upwards of 80% of the time when you see a patient's medication there are discrepancies between what's on that list and what patients are actually taking. So being able to sit down as part of a consent discussion and ongoing care and talk about everything that a patient's taking is really important. 

My background, I am a bone marrow transplant, stem cell transplant and cellular therapist. Just this last weekend I was on the inpatient service and a patient had brought in food from home which we completely are supportive of. The patient brought in a bunch of superfood shakes that she had bought at Costco and then some CBD tea and she asked us if it was okay if she could take those. And as we reviewed them and what was in all of those shakes and then what was in the CBD tea, there were major interactions between those supplements or those herbal remedies, and then what was in the medications we were giving in the hospital, so it was important. And she told us - it wasn't like I sat down and and was the shining example here, but it was helpful that we were able to take her global picture of what she was taking from a medication standpoint and be able to make sure that we were treating her in a safe manner and making sure that we weren't inadvertently causing harm. 

So, those are some of the things that we talked about. So, at every patient visit, and especially the first time you meet a patient you’re going to start therapy to be able to go over all of the different substances that patients are taking to make sure that they're safe. 

Brittany Harvey: Thank you so much for reviewing those key standards and key updates and that example of how important it is to review all of medications and herbal supplements that patients are taking to ensure safe care for our patients. 

So then following that, Amy, for domain three, what are the key points regarding ordering, preparing, dispensing and administering oral and parenteral antineoplastic therapy in a healthcare facility organization or in the home?

Amy Evers: So, domain three, actually, it was the domain that had probably the biggest discussion and fruitful debate between the panel members, but I think that we had some really great discussions and I think we had brought some really good changes and updates to the standards here. So domain three is where all of the verification standards live. So this is for practices who would either have been through the QOPI certification process or have been QOPI certified. This is where the surveyor actually will observe in real time how the clinical orders are reviewed by staff, how the drugs are prepared by pharmacy, and then how the drugs are checked one final time at the chair side or bedside immediately prior to administration. 

So as I mentioned earlier, antineoplastic therapies are being given more frequently in the home or in settings where there may not be two clinical staff members present. In this post-COVID world, we're finding patients can be treated safely in the home, but the standards didn't really reflect kind of these changes in where patients are receiving treatment. And often, more and more practices are relying on technology to supplement the verification process both either in the pharmacy setting where there may be a centralized pharmacist verifying the drug mixing process for multiple sites, or in the actual home setting where a nurse can connect virtually with another clinician to verify a drug immediately or administration. So the standards were updated to include these workflows. And I think it's becoming more and more commonplace, but how do we do this in a safe and effective way where we're ensuring that all of these same safe handling processes are completed, regardless of where the patient may be seeking treatment? 

So previous versions of the standards had three verifications. The first was before the actual preparation of the drug that someone other than the provider who wrote the order is verifying the order for all of the correct elements. The second verification is what usually happens in the pharmacy, upon preparation, what's being checked by the pharmacist or pharmacy technician who's preparing the drug. And then a third verification is done at, generally, the chair side where they're doing one final check of the orders to the drug to the patient. 

So with this update, we actually broke out that third verification into a fourth verification. So the third verification is that check with the drug in the order by the administering and then a second verifier. And then the fourth verification is actually the one where the patient’s involved in the verification. So there are two clinicians making that final double check with the patient immediately upon preparation, which I think is important and is reflective of this change that we're seeing more drugs being administered in the home setting. The chair side or bedside final verification was also expanded to include a visual inspection of the administration tubing, this is sometimes referred to as tracing the lines, which ensures that the drug is being accurately infused, that there aren't any loose connections, that the clamps are open etc. And I think this is something that most nurses do in their normal clinical practice, but I think adding this as an actual check in the verification process, is really important. And I know personally, I was really happy to see this added in as a formal check.

Dr. Bradley Hunter: Yes, thanks, Amy. One other new standard within domain three is regarding immunomodulatory or immune effector cell therapies that have the risk of cytokine release syndrome and how we build a framework to try to mitigate those toxicities. We really wanted to try to make a set of standards that would apply whether or not you’re at a coronary care center, like Penn or whether you were at a center, like within Intermountain Health, it's a small rural outreach center that you're trying to be able to get patients to care. So really, the main thing within dealing with therapies that have the risk of cytokine release syndrome is really just building a framework that there's a management policy that's present from the institution, and that it's up to date, it's following what we know will work for these therapies in order to mitigate their toxicity, and then also making sure that adequate antidote therapy, whether for example, for cytokine release syndrome, it could be tocilizumab or anakinra or other therapies, and that order sets are present to be able to follow along with the policy guidelines to guide clinicians wherever they are practicing to help mitigate cytokine release syndrome, neurologic toxicity, ICANS, or other sorts of therapies that are associated with these novel agents. 

Brittany Harvey: So for or the last domain, domain four, what are the key points for monitoring during and after antineoplastic therapy is administered, including adherence, toxicity, and complications?

Amy Evers: So domain four is pretty straightforward. It discusses the importance of assessing adherence and toxicities related to antineoplastic treatments. There wasn’t a whole lot of updates here. We did include having emerging treatment plans or equipment in the home and the healthcare setting. But what I really think is important and we need to underscore both with patients and clinicians, particularly as we've seen this rise in oral chemotherapy agents, is that a lot of times patients forget that this is the same chemotherapy that they're getting in the infusion suite. They're just taking it in a pill form. And I think patients forget that their adherence is just as important in taking that pill regularly and as prescribed. Financial toxicity is a real problem for most of our patients. Some of these drugs cost hundreds if not thousands of dollars for one treatment plan. As clinicians we've all heard stories of these patients who try to extend their prescription so they'll take a pill every other day instead of daily as prescribed, which really doesn't let the drug do what it's supposed to do. So I think when we talk about adherence, it's not just asking a patient whether they've taken their drug, it's about whether or not oral therapy is even appropriate for that particular patient. Do they have memory problems? Do they have metastatic disease to the brain where they may not be able to follow a complicated oral regimen? Do they have arthritis where opening a pill container is difficult? So having these conversations before a drug is even prescribed and making sure that it's the right route of administration for a patient is just as important as ensuring that they're maintaining their adherence to that drug. 

And oftentimes, the toxicities of these oral drugs are worse than what's actually being administered in some of the infusion clinics, and so making sure that we're checking in on these patients regularly to ensure that they're not having any toxicities that aren't being managed appropriately. Or if there may be toxicities that would require a dose reduction, or perhaps switching to a different drug entirely. So, even though it's a pretty simple and straightforward domain, I think it's really important that we're educating our clinicians and our patients about the importance of adherence. 

Dr. Bradley Hunter: I completely agree with what Amy said. She said it so well. I just want to echo back a couple of things that she said. Historically, we use the word non-compliant, which I think kind of sounds terrible to describe the patient's adherence to medication. I think part of this domain is recognizing that there is an entire environment that has to do with the patient that influences the way they're able to take their medication whether that's financial toxicity; we were talking to two people in our clinic who are professional financial toxicologists, and their entire job description is to help people get drugs for less so that they can actually take the side effects. If a patient feels terrible at that time, they’re not going to take it. So, understanding these barriers and really understanding the patient's entire picture, when you're figuring out how is the treatment plan going to match up with their reality, I think is super important. 

When it comes to site of care, we just want to make sure also that whether you're getting chemo at home or you’re getting chemo in the clinic down the street, or in a coronary care center, that there is a policy in place to respond to an emergency, but also the equipment available in all of those sites of care that you can respond. And that's another aspect that we wanted to make sure we hit in the domain as there's been so many changes in how patients get care in the last eight years.

Brittany Harvey: Absolutely. Recognizing the barriers and factors that impact the ability of an individual to receive the right therapy is crucial. And I want to thank you both for reviewing all of the standards and updates through all four domains. 

So then following that, in your view, how will these updated standards impact clinicians?

Dr. Bradley Hunter: It's our hope that these standards will guide the development of treatment infrastructure and help clinicians avoid error prone environments. We hope they're going to guide training efforts and that they will help clinicians ensure that they have relevant and accurate information about their patients and are able to respond appropriately when emergencies or even urgencies arise. Because of COVID, there's been such high staff turnover. And in the midst of all of this change, it's difficult to maintain a culture of safety when you've lost a lot of institutional knowledge of how to deal with that. And so, really trying to help bring people together again to have an infrastructure in place that makes training as seamless as possible and deal with the historical high staff turnover we’ve had. 

So we're again, hopeful that we're helping to create a framework that cancer centers, treatment centers can use, whether they are a coronary care center in a large academic space, or whether they're in a rural tele-oncology space to be able to use the standards to create a space and a place and experience for cancer patients in which they’re kept safe and we’re maximizing the benefit of their chemotherapy, their antineoplastic agents, and also minimizing the risk just to optimize benefits for the patient. 

Brittany Harvey: Definitely. Those are key points to provide a framework for clinicians. 

So then along those same lines, finally, what does this update mean for patients receiving antineoplastic therapy? 

Amy Evers: So while these standards are not necessarily patient facing, what I hope that this update will do, or actually not do, is that a patient shouldn't recognize any change in how they are cared for, regardless of what setting that they're receiving treatment. So whether it's at home, whether it's an ambulatory infusion center or in the hospital, they're still going to receive that same level of high quality care while they're receiving treatment. And I think that that's the most important thing that they should take away from this.

Brittany Harvey: Absolutely. 

So I want to thank you both so much for all of your work on these standards to ensure patients receive optimal safe and effective care. And I want to thank you both so much for your time today. 

Amy Evers: Thank you so much.  

Dr. Bradley Hunter: Yeah, thank you. It’s really great to talk about this stuff. 

Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the complete standards go to www.asco.org/standards. 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. Rachel Freedman and Dr. Sharon Giordano share the latest rapid guideline update from ASCO on the adjuvant use of the CDK4/6 inhibitors abemaciclib and ribociclib in patients with stage II and III breast cancer. They share details on the impetus for the update, supporting evidence, and considerations of benefits and harms for individuals. Additionally, Drs. Freedman and Giordano discuss what these options mean for clinicians and patients, and outstanding questions regarding optimal adjuvant chemotherapy and targeted therapy for patients with early breast cancer.
Read the full rapid update, “Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer – CDK4/6 Inhibitors: 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.24.00886 

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. Rachel Freedman from Dana Farber Cancer Institute and Dr. Sharon Giordano from MD Anderson Cancer Center, co-chairs on “Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer – CDK 4/6 Inhibitors: ASCO Rapid Guideline Update.” Thank you for being here, Dr. Freedman and Dr. Giordano.

Dr. Rachel Freedman: Hi. It's great to be here, thank you.

Dr. Sharon Giordano: Yeah, thank you for having us.

Brittany Harvey: Great. Then, 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. Freedman and Dr. Giordano, 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. Freedman, what prompted this update to the “Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer Guideline”, which was previously updated in 2021?

Dr. Rachel Freedman: Yeah, at that time, we published guidelines which were part of an amendment to the previously published 2020 early breast cancer guidelines to include consideration of adjuvant CDK4/6 inhibitor use, because the first data for adjuvant abemaciclib became available from the monarchE trial, and because the FDA had acted to grant approval for the use of abemaciclib in those with node positive disease and a Ki-67 score of at least 20%. Our recommendation at that time was to apply abemaciclib in the greater context of the intention-to-treat population included on the monarchE study.

But since that time, the FDA in 2023 expanded its approval for adjuvant abemaciclib for a broader population, removing that Ki-67 requirement that was a part of their initial approval. With this change, the recently published longer term data from the monarchE study and the recently published data from the NATALEE trial and adjuvant ribociclib study, we felt that it was time to update our guidelines to be more relevant to the most current data available.

Brittany Harvey: I appreciate you providing that background information on the impetus for this latest update.

So then, Dr. Giordano, based on this new data, what are the updated recommendations in the latest version of this guideline?

Dr. Sharon Giordano: So we really have two updated recommendations and then two qualifying statements that go with the new recommendations. So the first recommendation focuses on the use of adjuvant abemaciclib, which, as Rachel noted, was included in our previous guideline. So this recommendation is that abemaciclib for two years plus endocrine therapy for five or more years may be offered to patients who meet the criteria of the intent-to-treat analysis in the monarchE study. These are patients with resected, hormone receptor-positive, HER2-negative, node-positive breast cancer at high risk of recurrence. The way the study defined the high risk of recurrence was having either four or more lymph nodes involved, axillary lymph nodes involved, or having one to three lymph nodes, plus other high risk features, which included having a grade three tumor the size of 5 cm or greater, or having a Ki-67 of more than 20%. And so, although the FDA has dropped the requirement for the Ki-67 testing, and the language is quite broad now, the panel recommends the use of abemaciclib, really in that subgroup of patients that would have been eligible for the original monarchE study. That's the first recommendation, kind of a long one, but that was the update.

The second recommendation focuses on the use of adjuvant ribociclib, and this is based on the data from the phase three NATALEE trial that was recently published. This recommendation is that ribociclib for three years plus endocrine therapy, may be offered to patients with stage two or three breast cancer who would have met criteria for study entry and have a high risk of recurrence. I would note with this one, I think it's important to remember that the ribociclib that's used in the adjuvant setting is a different dosing. So it's 400 milligrams daily, three weeks on, one week off, as compared to the 600 milligrams we're using in the metastatic setting. That was the second new recommendation.

As I previously mentioned, however, there were two qualifying statements. The first qualifying statement was really the panel wanted to make, because they felt that CDK4/6 therapy in the adjuvant setting may not provide meaningful clinical benefit to every single patient who would have been eligible for these two trials. The concern was especially around lower risk patients. So the early stage two breast cancer patients who were included in the NATALEE trial, and in that situation, the panel felt for some patients, the risks may outweigh the benefits. The challenge here really was that there was not a great way to pick a very specific subgroup of patient that would benefit or wouldn't benefit. So based on that, the panel really recommended taking a broad approach and considering the benefits of therapy, the risks, the costs, and of course, patient preference when making the decision about whether or not to offer these drugs in the adjuvant setting.

Then the second qualifying statement was really around how to pick between the two drugs. What the panel stated was that for patients that met the criteria for both studies, they could have been in either monarchE or NATALEE, for those patients, that abemaciclib has longer follow up, has a deepening benefit over time, it's more convenient because it's two years versus three years, and it has FDA approval. So for patients, again, that would have met criteria for either study, the panel favored using abemaciclib, except if patients had some contraindication or intolerance. That is the update, both the recommendations and the qualifying statements in this updated guideline.

Brittany Harvey: Understood. Thank you for reviewing both of those recommendations and the nuances between choosing between some of those options as detailed in the qualifying statements.

So then, Dr. Freedman, I think Dr. Giordano has talked about this already a little bit, but what should clinicians know as they implement these new recommendations into practice?

Dr. Rachel Freedman: Yeah, in the guidelines, as Sharon said, we've really tried to offer recommendations that balance the available efficacy data along with the toxicity data and even some mention of cost consideration, although we purposely can't address that in the guideline. And we just feel that all of these need to be considered in combination for the individual patient. And just like you heard, our panel felt that for those meeting criteria for both the monarchE and NATALEE trials, given all the reasons that Sharon explained, that abemaciclib may be the preferred agent for now, but we all look forward to the evolving data in this space. It's great to have another evidence-based option with ribociclib at this time, but we really acknowledge that longer term follow up will evolve these recommendations further.

Brittany Harvey: Absolutely. As you mentioned, it's great to have another option in this space.

So then, in your view, Dr. Giordano, how will these recommendations impact patients with early breast cancer?

Dr. Sharon Giordano: I think that, overall, this is really good news for patients who are at high risk because there's now two new available therapies that they can use to help prevent recurrence. I will note, as we mentioned before, though, they do come with a price, both the cost of the drug and the additional side effects of having two or three years of an additional drug that they're taking. But having said that, I think it's always good to have new options for therapy, and we can discuss these options with the individual patients, weigh the risks and the benefits, and ultimately, we hope with longer follow up, it would be great to see if these drugs would actually improve overall survival, which is ultimately our biggest goal.

Brittany Harvey: Definitely, those are key for shared decision making between patients and their clinicians.

Then finally, looking forward, Dr. Freedman, what are the outstanding questions regarding the optimal adjuvant chemotherapy and targeted therapy for early breast cancer?

Dr. Rachel Freedman: Well, there are a lot of outstanding questions with regard to chemotherapy. We have a lot of questions. We still have insufficient data to specify which subgroups, who may have a higher degree of nodal involvement, or what we call anatomical risk, but perhaps a favorable biology or genomics. And we don't know which subgroups still need chemotherapy. And I think this is a group many of us are struggling with in the clinic, is what to do when you have high anatomical risk, but a well behaving cancer, so to speak. And I think that's a burning question for many of us.

I still think we have room to improve our adjuvant regimens and figuring out who needs more and who needs less therapy when we are going to move forward with chemotherapy. And we also, with regard to CDK4/6 inhibition, have a lot of ongoing questions. There are a lot of patients who may not benefit from CDK4/6 inhibition as much as others, and the broader population on the NATALEE trial allows us to explore this a little bit, but we're cautious about interpretation of subgroups. But the lowest risk patients on the NATALEE trial may be a group of patients that it's really important to think about when it comes to balancing that toxicity and efficacy risk, as opposed to that higher risk patient where you're sure you want to move ahead.

And I think we really await the survival data from both NATALEE and monarchE, neither of which have shown a statistically significant survival advantage to date. We really need ongoing follow up of these studies, and we look forward to learning more in the years to come.

Dr. Sharon Giordano: Yeah, I completely agree. It's very well said. I mean, I think one of the biggest challenges, as Rachel said, it's really hard to figure out which subset of patients are truly going to benefit and have the benefit of the drug outweigh the side effects. I hope as we get longer follow up on the studies and additional data come out, we're able to get more information so that we can really give the best therapies to the patients that need it, but also spare patients who don't need it from the additional side effects.

Brittany Harvey: Absolutely. We'll await the longer term follow up of these trials and then future updates to these guidelines.

So I want to thank you so much for your work to rapidly update this breast cancer guideline. And thank you so much for your time today, Dr. Giordano and Dr. Freedman.

Dr. Rachel Freedman: Thanks so much.

Dr. Sharon Giordano: Yeah, thank you very much, our pleasure.

Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full rapid recommendation update, 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'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. Karen Mustian joins us to share the latest update to the management of fatigue in adult survivors of cancer guideline from the American Society of Clinical Oncology and the Society for Integrative Oncology. Dr. Mustian highlights the recommendations across the continuum of care, including recommendations for patients with cancer-related fatigue during active treatment, after treatment, and for patients with advanced cancer or at the end of life. She also discusses interventions that are not recommended for treating cancer-related fatigue. The episode wraps up discussing the importance of this guideline for clinicians and patients, and a call for more research both on interventions and on dissemination and implementation to improve symptom management for cancer-related fatigue.
Read the full guideline update, “Management of Fatigue in Adult Survivors of Cancer: ASCO-SIO Guideline Update” at www.asco.org/survivorship-guidelines.

TRANSCRIPT

This guideline, clinical tools, and resources are available at www.asco.org/survivorship-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.24.00541 

 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. Karen Mustian from the University of Rochester School of Medicine and Wilmot Cancer Institute in New York, co-chair on “Management of Fatigue in Adult Survivors of Cancer: American Society of Clinical Oncology –Society for Integrative Oncology Guideline.” Thank you for being here, Dr. Mustian.

Dr. Karen Mustian: Thank you for having me, Brittany.

Brittany Harvey: Then, 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. Mustian, 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 then, to dive into the content of this episode, Dr. Mustian, what is the purpose and scope of this updated guideline on fatigue in adult survivors of cancer?

Dr. Karen Mustian: Cancer-related fatigue is one of the most common and debilitating consequences that patients experience when they go through treatment, and it can actually interfere with their ability to complete treatment and their recovery along the way. And it's not the same as a typical fatigue that you might experience from physical activity, let's say, where you can come back in and rest for a little while or take a nap or sleep, and you wake up refreshed and not feeling fatigued anymore. This type of fatigue actually needs special attention and needs to be treated with therapies.  

So, this particular guideline is developed in a manner to help clinicians when patients present with fatigue, especially moderate to severe fatigue, that can be very debilitating, help patients decide what kinds of treatments they can use to reduce this fatigue. It's really important that this fatigue be reduced for a number of reasons. But some of the reasons we think of as being really critical are so that they can actually get their full treatment as prescribed, and then when finished with treatment, so they can actually resume their normal daily activities. They can keep working, they can keep engaging with their families, they can resume all those wonderful normal life activities that we hope for and that their prognosis will be a good one.

Brittany Harvey: Absolutely. It's critical to address cancer-related fatigue for all adults with cancer. 

Then, this guideline covers three distinct patient populations and provides recommendations for each. Starting with the first section, what are the key recommendations for patients with cancer-related fatigue during active treatment?

Dr. Karen Mustian: Well, one of the things I want to mention about this guideline before I answer that question is this guideline encompasses the entire cancer trajectory. In previous guidelines for treating fatigue, we really focused on how to work with patients once they had completed their primary treatments for their cancer. This time, we're able, because the research and the literature have advanced more, to really now address what we should be doing to help patients with their fatigue while they're receiving active treatment. This can be primary treatment and/or maintenance therapies, but then also once they're done with treatment and they are in the recovery stage. And then also the third area is how should we help patients with advanced cancers with their fatigue that they are experiencing? 

And I believe that you just asked me how we should be working with patients really during active treatment. This guideline, when we reviewed the literature, there's really good evidence to suggest that for people undergoing cancer treatment, clinicians should recommend exercise, cognitive-behavioral therapy, mindfulness-based programs, and Tai Chi or Qigong as first-line therapy to reduce the severity of fatigue that patients can experience during treatment. We also found that the literature suggests that psychoeducation and American ginseng may also be recommended in adults undergoing cancer treatment.

Brittany Harvey: Understood. Thank you for providing those key recommendations for patients with cancer-related fatigue during active treatment. 

Then, following those recommendations, at the next point in the cancer trajectory, what does the expert panel recommend for patients with cancer-related fatigue after treatment?

Dr. Karen Mustian: Well, for survivors after treatment, the literature is also strong in that clinicians should be recommending also exercise, again, cognitive-behavioral therapy, and mindfulness-based interventions and programs. There's also a good amount of data to suggest that we should be recommending yoga, acupressure, and moxibustion for cancer-related fatigue after completion of treatment.

Brittany Harvey: I appreciate you reviewing those recommendations as well. 

Then that final third population that you previously mentioned, what are the key points for the management of cancer-related fatigue for patients with advanced cancer or at the end of life?

Dr. Karen Mustian: For patients at the end of life, we should be offering those individuals cognitive-behavioral therapy and corticosteroids.

Brittany Harvey: Thank you for reviewing all of those recommendations for patients with cancer-related fatigue during active treatment, after their treatment, and for patients with advanced cancer. 

Are there additional recommendations that were made by the expert panel that we should know about treating cancer-related fatigue? Recommendations for things that we should not be doing to treat cancer-related fatigue?

Dr. Karen Mustian: One of the things that's also characteristically different about this particular guideline update for ASCO is that this time we actually have research to suggest that there are some interventions that historically may have been used, but the research is actually suggesting that they should not be recommended at this time. The guidelines now state that clinicians should not recommend L-carnitine or antidepressants, wakefulness agents, or routinely recommend psychostimulants to manage symptoms of cancer-related fatigue. One of the things that this really highlights is the recommendation to pull back on the use of pharmaceutical products as a first-line therapy for treating fatigue and to really look at behavioral interventions which are showing the strongest evidence in the research in terms of effectiveness, both during treatment, after treatment, and for our patients with advanced cancer, and to really promote these behavioral interventions for patients rather than just reaching right for that pharmaceutical product. 

There are still instances where pharmaceuticals may be really important for patients, such as if someone tries behavioral therapies and they fail, for example, or if someone has fatigue that is just absolutely so severe that they cannot even give a good effort or attempt to trying something like exercise or cognitive-behavioral therapy or mindfulness-based programs. You know, even considering that most of the cognitive-behavioral therapy and mindfulness-based programs don't require physical activity, they're very low intensity types of behavior change. And that's really a big area where these guidelines also differ in the update from previous guidelines. 

Brittany Harvey: Absolutely. I appreciate you reviewing those so that we know what strategies and treatments also should not be used and how we need to tailor our interventions to specific patients and their needs. 

So then, in your view, Dr. Mustian, what is the importance of this guideline and how will it impact both clinicians and patients with cancer-related fatigue?

Dr. Karen Mustian: I've seen a lot of ASCO guidelines and helped with a lot of ASCO guidelines, and one of the things that I think is really great about this particular guideline for cancer-related fatigue is, I'll reiterate, this is one of the most prevalent, debilitating toxicities experienced by virtually all cancer patients at some point during their time being treated or in recovery. And I'm really pleased to see that the research has come far enough that we now actually have interventions that we can recommend strongly, and then we also have other interventions that we recommend that the evidence is still growing for. 

What's also nice about this, and what's really going to be impactful for patients, as I just said, is that the recommendations are not focused on pharmaceuticals. Patients already take a lot of pharmaceutical products, we have to worry about polypharmacy and all the side effects associated with that, especially in our elderly populations. This guideline gives clinicians and patients not just one or two, but several behavioral interventions that they can use that, if used in the correct way, as stated in the guidelines, stand an excellent chance of reducing the amount of fatigue that they experience. So, it really is going to change the landscape of care for patients. It's also going to change the landscape of what clinicians have to offer in their toolkit for treating patients.

And I know that oftentimes we think it's easy for a physician to recommend a pharmaceutical product. But I also know that a lot of oncologists love being able to recommend lifestyle interventions to really help their patients with side effects and toxicities. And that's exactly what this guideline is offering. And I think it's just going to provide a wonderful place for a clinician and patients to come together to have conversations about what the guidelines say is effective, and to allow them to have a conversation surrounding choice. Which one seems to be the best fit? Which one would a patient actually like to try? Which of these lifestyle interventions does the patient think they have the best chance of succeeding with both in terms of accessing it in their community, adhering to it, being able to do it so that they can actually derive the benefits that we expect to see. That's really one of the key components of the efficacy of these interventions as well, is what really is going to determine, ultimately, how well these interventions work is working together to pick the one that the patient feels that they can actually do and accomplish in order to receive the benefits. It really is going to change the landscape of how we work with symptom management surrounding fatigue.

Brittany Harvey: Yes. As you mentioned, it's great to have these multiple evidence-based recommendations to have a real impact for patients. You also just noted that evidence is still growing in some areas. So what future research is needed regarding the management of cancer-related fatigue in adult survivors of cancer? 

Dr. Karen Mustian: I think oftentimes when we see a guideline come out, many times people say, “Well, we have the answers now, so we don't need to fund any more research in that area.” Or maybe it becomes less of a priority. For all that we do have these treatments to recommend now, we're still really very in the early stages of being able to identify, characterize and accurately provide therapies and treatments for cancer-related fatigue. When I look back at the history of nausea and vomiting and where we've come in the decades of research that has ensued since the first initial findings on that. I think fatigue is still very much in its early years.  

Some of the things that we still don't necessarily know when it comes to these kinds of interventions, and I can tell you we struggled with in the guideline committee, is what is the actual dose of some of these behavioral interventions? I think when we prescribe a medicine, we think, “Oh, you need this particular dosage of this particular agent. You take it this many times a day, this many times a week for x number of weeks, and there you go.” With behavioral interventions, it's a little more complex. And so really getting down to the nitty-gritty of defining exactly what type of exercise, the intensity of that exercise, exactly how many minutes a day, exactly how many minutes a week do you have to do? We weren't really able to get our recommendations refined to that degree, and I think future research that really wants to be in service of clinicians and patients should work towards defining specific prescriptions of these interventions.  

Exercise, I just gave that example, but it's the similar kind of approach for cognitive-behavioral therapy. What are the specific components that need to be included? What does the ratio of focus on those different components need to look like? Also, the same with Tai Chi, Qigong moxibustion, acupressure that we mentioned - really refining those specific prescriptions, I think, is something that we need research on, and that will take us to the next step, where we have patients doing enough that they get the effect that they want, but not wasting their time, effort, energy, and finances doing too much that they don't need to do in order to achieve the benefit that we hope for.  

For some of the recommendations that are not strong, we still need large, definitive, randomized clinical trials on those interventions. So, for example, we talk about that we may recommend psychoeducation and American Ginseng for patients undergoing cancer treatment. We need more research in that area in order to be able to really say whether or not we should be offering that for patients undergoing treatment. And specifically, those large, definitive, phase III randomized clinical trials, talking about trials that also could be done across multiple centers where we can have more generalizable populations, different kinds of communities where those interventions are being delivered, rural dwelling communities, for example. And then, of course, there's always the need for newer and better interventions. Some of these interventions have very decent effect sizes in terms of their outcome, but it would be wonderful to actually find an intervention that completely mitigated cancer-related fatigue, and it was completely gone, never to return. I think we're still in some ways waiting for that intervention to be developed. And I also would say, even though we're not recommending pharmaceuticals quite a lot in this guideline, they're not our first-line therapy, there's still always the opportunity to identify molecular targets that really could help with remediating cancer-related fatigue. So there's still a plethora of research to be done out there and things that we don't know.  

And then lastly, and very much importantly, we need to do research and dissemination and implementation. Behavioral interventions are really challenging to deliver. So unlike a doctor recommending a pharmaceutical product where they can write a prescription, and then the patient gets the prescription from the pharmacy and they have what they need, supposedly understanding how to prescribe these interventions for patients, or even understanding how to refer them to places in communities where they can actually get a credible practitioner that is using an evidence-based approach that is known for being one of the types of yoga or exercise, or mindfulness-based stress reduction or CBT, that will actually have a positive influence on fatigue is also challenging. And so we need that dissemination and implementation research  - that I do believe is going to be also really key in the next decade at changing the landscape of what this toxicity looks like in the patient experience of cancer.

Brittany Harvey: Definitely, these all will be key to understanding the best options for all patients, and we'll look forward to continued research in these areas to fuel future guideline updates and improve management of cancer-related fatigue in all adults with cancer. 

So, I want to thank you so much for your work developing this guideline, and thank you for your time today, Dr. Mustian.

Dr. Karen Mustian: Oh, it's such a pleasure. I did not develop this guideline alone. I definitely want to say thank you to all my colleagues who worked very diligently and very hard on digesting the research and making these recommendations. They are representative from institutions all across the United States. A very wonderful expert panel. Thank all of them very much and give them the credit that they are due for all their hard work. And thank ASCO for supporting these efforts for clinicians and patients. And Brittany, thank you very much for having me.

Brittany Harvey: Absolutely. A big thank you to the whole panel.  

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