Mar 2, 2020
In the latest ASCO in Action Podcast, American Society of Clinical Oncology (ASCO) CEO Dr. Clifford A. Hudis is joined by ASCO Chief Medical Officer Dr. Richard Schilsky to discuss the recently released 2020 Clinical Cancer Advances report, which named the refinement of surgical treatments for cancer as the Advance of the Year.
“A lot of the advances we’re seeing in surgical approaches now are driven by better systemic therapies for cancer. These systemic treatments have improved survival outcomes and quality of life for our patients, and have now begun to transform the role of surgery in cancer management by reducing the amount of surgery in some cases, eliminating the need for it in others, or, conversely, increasing the number of patients who could undergo surgery when it’s needed for treatment of their cancer,” says Dr. Schilsky.
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 this ASCO in Action podcast brought to you by the ASCO Podcast Network. This is a collection of nine programs covering a wide range of educational and scientific content and offering enriching insights into the world of cancer care. You can find all of ASCO's podcasts, including this one, at podcast.asco.org. The ASCO in Action podcast is ASCO's podcast series that explores 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 Clifford Hudis, and I'm the CEO of ASCO, as well as the host of this series, and I'm delighted today to have as my guest the Society's Chief Medical Officer and Executive Vice President, Dr. Richard Schilsky. He's also an executive editor for the recently released 2020 Clinical Cancer Advances Report. In this report, ASCO identifies the most important clinical research advances of the past year across the full trajectory of the disease, from prevention and screening, to treatment and survivorship. The report also announces ASCO's Advance of the Year and updates our list of research priorities that have great potential to accelerate progress against cancer. Rich, welcome, and thank you for joining me today.
Dr. Richard Schilsky: Thanks a lot, Cliff.
Dr. Clifford Hudis: Now, starting at the beginning, this year ASCO has recognized refinement of surgical treatment of cancer as the Advance of the Year, and this is an area of clinical cancer research that has demonstrated the most significant progress in a year's time. I have to say, before we get into that, it seems almost poetic to me that this has happened this year because, one, we lost a leading surgical investigator in our field, Bernie Fisher, this year, and two, as I think about it, it came as a little bit of a surprise to me only because the mid 19th century was really the beginning of the century of surgery, and surgery for cancer dates back to Roman and Greek times, actually. So, can you tell us, in light of all of that, what was it that brought this back to the fore this year?
Dr. Richard Schilsky: Over the years, we've seen a great deal of progress in developing the new systemic therapies for cancer, and this really, I think, illustrates the prescient work of Bernie Fisher in his seminal research on adjuvant therapy for breast cancer, because a lot of the advances that we're seeing in surgical approaches now are driven by better systemic therapies for cancer. These treatments have improved survival outcomes and quality of life for our patients, and they've now begun to transform the role of surgery in cancer management by reducing the amounts of surgery in some cases, and even eliminating the need for it in others. Or conversely, increasing the number of patients who can undergo surgery when, in fact, it is needed to help in the treatment of their cancer.
Dr. Clifford Hudis: That's great to hear, because I was wondering at first if it was simply the fact that we just had a president who was a surgeon, and it's clearly about much more than that. What are some are the specific advances that you actually would cite as supporting this call out of surgery this year?
Dr. Richard Schilsky: Yeah, I think there some really interesting reports that are summarized in this year's Clinical Cancer Advances that really speak to this issue. In melanoma, for example, there are two studies that examine the efficacy and safety of neoadjuvant treatments for patients with locally advanced disease. Australian researchers examined the combination of two molecularly targeted drugs, dabrafenib and trametinib, given before surgery in patients with stage 3c melanoma that has BRAF V600 mutation. Not only did 86% of patients on the trial respond by the time of resection, but almost half had a complete response, either obviating the need for or simplifying the surgical treatment.
In another study, patients with stage three melanoma that was still treatable with surgery received ipilimumab and nivolumab for two cycles prior to surgery, resulting in a pathologic response rate of 77%. These studies are already changing practice, helping patients with locally advanced melanoma avoid surgery in many cases, or making surgery possible in patients with locally advanced disease who might not otherwise have been candidates for surgical resection. So this really is the year, I think, where we're seeing highly effective systemic therapies making surgery more possible where surgery can contribute to achieving better cure rates, or obviating the need for surgery where surgery is actually no longer necessary given the effectiveness of systemic treatment.
Dr. Clifford Hudis: From your point of view, as you look at both our Clinical Cancer Advances for this year and also the totality of public health data, what role would you ascribe to federal funding in generating these advances?
Dr. Richard Schilsky: Well, I think it's pretty clear that essentially every cancer advance begins in the basic science laboratory. It begins with new discovery, new understanding of biology, new description of mechanism of cancer progression, and the identification of novel cancer targets, and all of that basic research that's funded by NCI and NIH more broadly is the foundation for all the progress that we've made in development of new therapies, as well as prevention strategies and early detection strategies and so on. So, the federal funding is critical.
This year's Clinical Cancer Advances Report highlights 10 studies that were supported, directly or in part, by funding from the NIH, so that highlights another important role for the federal funding. Not only is there the discovery work, but there is also the work through NCI-funded cooperative group studies and other clinical trials that actually is helping to translate those basic science discoveries into clinical trials, and more importantly, helping to design clinical trials that are not likely to be pursued by commercial interests, but that answer important clinical questions that directly impact the way patients are treated by their physicians.
Dr. Clifford Hudis: This is the second year that ASCO has included with its Clinical Cancer Advances Report a specific set of research priorities. Can you tell us a little bit about the motivation for creating this so-called research agenda for the country, and then the criteria that are used to select these specific priorities?
Dr. Richard Schilsky: Well, as you said, as much progress as we're making, there still is substantial unmet need, and so we need to continue to accelerate progress in many areas and focus our resources, so we launched ASCO's list of research priorities to accelerate progress against cancer by sparking momentum in those areas of research where the opportunity is really ripe to spur new advances. The goal in doing this is to provide the cancer community with direction, or at least insight as to where to focus their investments and resources. The research priorities represent areas that have the potential to significantly improve the knowledge base for clinical decision-making and help us address vital needs in cancer care that remain unfulfilled.
Dr. Clifford Hudis: Now, these priorities are nominated by ASCO volunteers and clinical experts who've worked on the Clinical Cancer Advances Report and have identified not only what the big advances are for the year, but what the unmet needs are, where the opportunities still lie to continue to accelerate our research momentum. So, they were then discussed and distilled and evaluated by various groups of ASCO experts, and what's now in the report represents our best current thinking about where we have opportunities to really have a big impact.
And I think, if I'm not mistaken, one of the hopes for results of this is to recognize that there are areas that get a lot of research. We know there are literally more than 100 I-O drugs theoretically in development right now around the world. Our goal here, I think, is to highlight some of the areas that may not be supported directly by industry necessarily, but in fact, may be dismissed as people think about high-impact targets. There are some places where we need to make progress in order to offer the most patients the greatest benefit.
Dr. Richard Schilsky: I think the research priorities are not necessarily what might be thought of as underrepresented areas of research, but they are areas where ASCO feels that there is opportunity to have a big impact, because there's already sort of a glimmer of progress being made in these areas, and we believe that with further investment and prioritization, we can really much more rapidly accelerate progress in these areas. And the research priorities are by intention fairly broadly stated, because we're talking in the research priorities not necessarily about a specific disease or a specific target, but really a specific approach or an area where we believe we can have broad impact by focusing on a specific population or a way in which we can use therapy more effectively or with less toxicity.
Dr. Clifford Hudis: So as an example, and just making it up, but a difficult to treat disease where there is not, again, meaningful scientific advance actually wouldn't make the list because there's not really an opportunity right now in our minds, right?
Dr. Richard Schilsky: Absolutely. And in fact, when you look at the list, you'll see that there are no specific cancers that are called out in the list. The list is really about specific populations, specific approaches, ways in which we can better utilize available therapies or limit the toxicities of available therapies so that overall, the impact of treatment is greater for the particular patient population.
So then why don't we just dive right in and talk about what are some of the research priorities that made the list this year.
There are eight priorities this year. They really fall into three major thematic areas. The first of those is getting treatments to the patients who can benefit from them the most and sparing the toxicities and costs of treatment for the patients who would benefit the least. So, two priorities in that area are identifying strategies that predict response and resistance to immunotherapies.
So these are therapies that we already know can have an enduring impact on a small proportion of patients across a variety of different diseases, and the real question is, who are the patients who are likely to receive that long-term benefit, and who are the patients who are unlikely to benefit and understand why, but also if the patients are not going to benefit from those therapies to then turn to alternative treatments with fewer toxicities. Another priority in this area that sort of echoes of the advance of the year is to further understand how to limit the expensive surgery by optimizing systemic therapy, and this really gets back to the whole concept of adjuvant therapy in many ways, where we know that many patients who receive adjuvant therapy either don't need it or don't benefit from it. And what we want to be able to do is to tailor adjuvant therapy in such a way that it has the greatest impact on the population that needs it the most.
Now, the priorities are also focusing on improving treatment and care of special populations, emphasizing the importance of improving representation of these populations with clinical trials so that we actually have reliable data to better inform treatment approaches. A few priorities in this thematic area include increasing precision medicine research and treatment approaches in pediatric and other rare cancers, optimizing care for older adults with cancer, increasing equitable access to cancer clinical trials so that more patients can benefit from those studies, and importantly, reducing the adverse consequences of cancer treatment, particularly in long-term survivors who, in a sense, have to live with the consequences of their cancer and its treatment for the rest of their lives.
Finally, but not least, the research priorities focus on reducing the risk of cancer and on detecting it early. So, there is a priority on reducing obesity's impact on cancer incidence and outcomes, I know that's been of particular interest of yours for many years, and then on better identifying premalignant lesions and predicting when treatment is needed. We know from the natural history of many premalignant cancers that they never will evolve to invasive cancer, and so there's a risk of over-treating people based on a diagnosis of a pretty invasive cancer. We want to better understand the biology and natural history of those circumstances so that the patients who need treatment will get it and the patients who can safely forgo it can skip it.
Dr. Clifford Hudis: Yeah, and one can imagine in the years ahead that that will actually, if you will, leap into even low-grade, but invasive cancers and start to help us know who actually needs therapy and you can just have a cancer--
Dr. Richard Schilsky: Yeah, I'm sure you could do many hours of podcasting about DCIS and the controversy surrounding that type of cancer. Of course, the same is true in prostate cancer and other cancers that have a diverse natural history. There are clearly circumstances where patients who have early stage, but biologically indolent cancer may not need treatment or may not need aggressive treatment. We just have to be able to identify who those patients are.
Dr. Clifford Hudis: Right. So, for people who are intrigued by this, and I hope you are, I encourage you to take a look at the full and detailed list of the research agenda by visiting asco.org/cca. That's asco.org/cca, and there, you can take a deeper dive into all of these items. Now, Rich, if we were to succeed and direct the right resources to these priority areas, how would you see this actually transforming patient care in the next few years?
Dr. Richard Schilsky: Well, at a high level, I think it's-- we hope it'll dramatically change the care of cancer patients and allow more patients to get the right treatment at the right time, and of course, enabling them to live longer, fuller, better lives. It's really all about understanding the biology of each person's cancer, its likely natural history, its vulnerabilities, and then developing a treatment plan that is optimized for the care of that particular individual.
Dr. Clifford Hudis: Now, we recognize-- and we touched on this already-- that we can't do all of this within ASCO, and we don't have the ability to specifically direct research programs. So, what is it that would satisfy us that the cancer community is responding to this goading, if you will, and is trying to make progress? What would be the indicators that you would find?
Dr. Richard Schilsky: Well, as you said earlier, I mean, we continue to vigorously advocate for increasing federal funding for cancer research, which is the foundation of all the basic science breakthroughs that enable everything that flows from that in terms of development of new molecular diagnostics and treatments, so we want to continue to be aggressive in advocating for that improved funding. We clearly still need better prevention and screening approaches. We saw very little in the way-- other than vaccination, as we discussed earlier, and a few drugs, like some of the drugs that are approved to treat or reduce the risk of breast cancer in high-risk individuals, we saw very few effective prevention strategies. We need a lot more research on how to identify what those strategies might be and how to bring them to fruition.
We have a lot of opportunity that can really only be supported through federal funding to do what's often referred to as comparative effectiveness research. The pharmaceutical company's job is to bring new drugs to market, not to necessarily show which drug among many is the best drug for an individual person. And yet, we know that patients and doctors are confronted with these decisions all the time, particularly when there are several approved drugs in a given indication. Which is the best one to use, which is the least toxic, which is the one that's likely to produce the best outcomes for my particular patient? Those are questions that can be answered through comparative effectiveness studies that can be funded by federal funds.
And then finally. Breakthroughs on rare cancers. Rare cancers are not necessarily a focus for commercial drug development because they represent small markets. Now, we are beginning to see with the FDA approval of some histology agnostic drug approvals that even drugs that target very rare molecular alterations can potentially be attractive to the pharmaceutical industry. Because in the histology agnostic approval, it opens up a much broader market. But rare cancers otherwise are likely to not get the attention of commercial developers, and we need federal funding to support research in those areas, to be sure.
Dr. Clifford Hudis: So really, our hope with these priorities is that we stimulate the entirety of the research and treatment ecosystem to think about these studies, to support them, design them, and enroll patients on them given the opportunity, right?
Dr. Richard Schilsky: Well, that's exactly right. And the whole ecosystem has a role to play in bringing drugs from the discovery phase, through development, through ultimate commercialization, and then the effectiveness research then follows on after the commercialization so we really actually understand how the drugs perform in real-world populations, many of whom never get the opportunity to participate in the pivotal clinical trials.
So fundamentally, this can all be understood as advocacy. And in that regard, I guess it's reasonable, or at least our listeners may wonder what steps they and ASCO members in general can take to urge Congress to support these policies and support the critical cancer research that we're highlighting.
The easiest thing for ASCO members is to contact their members of Congress through ASCO's ACT, A-C-T, Network, which they can access at asco.org/actnetwork, and there, they can easily generate a letter advocating for federal support for cancer research to their congressmen and their senators. And I can't stress enough how important it is that all members get involved in this advocacy work. There are also opportunities for people to come to Washington to participate in ASCO's Hill days and to get involved in ASCO's other activities through the Government Relations Committee and other work that their society is doing on their behalf.
Dr. Clifford Hudis: Well, this is great. In just about a half an hour here, we've covered a large amount of material and a lot of progress. Maybe at the risk of some redundancy, what do you think, in summary, is the takeaway that you hope that listeners and everyone reading the Clinical Cancer Advances Report takes away?
Dr. Richard Schilsky: It's a bit hard for me to sort of grapple with this from time to time, but I've now been an oncologist for 40 years, and over the 40 years of my career, when you look at it through that broad span of time, I really feel like I've seen remarkable progress that we have made together in understanding cancer biology, developing far more effective and less toxic therapies, developing much better supportive care strategies, and we're now really beginning to see that at the population level with this substantial fall in cancer mortality rates that you alluded to earlier that's been occurring now year over year over year for at least the last two decades. And this year, as you suggested, it's being attributed, at least in part, to far more effective treatments for cancer than we've ever had in the past, particularly for lung cancer, which is still the nation's biggest cancer killer, but for which we have far better therapies than we've ever had before. All of this comes only from a sustained commitment to research, from having an ecosystem, as you suggested earlier, that's committed to making progress in every cancer type for every cancer patient. And I am remarkably optimistic as we now head into a new decade that the pace of progress is going to continue to accelerate in a very unprecedented way.
Dr. Clifford Hudis: Yeah, I agree. I mean, it's been interesting to watch the advances I think one of the places where we have to acknowledge frustration on the part of our members and community and the patients we serve is that the advances are often very pointed because of scientific breakthroughs, and they are profound, and meaningful, and they transform disease, but the totality of the burden of cancer remains substantial. For some reasons outside the scope of this discussion, it will even continue to grow on a global level. So, we have a challenge here to celebrate real advances while respecting the fact that we have a lot of progress ahead, right?
Dr. Richard Schilsky: Our work's not done, but it's gotten a lot easier, and in many ways, a lot more fulfilling.
Dr. Clifford Hudis: Well, Rich, I want to thank you again, both for leading the production of this report, and for joining me today on this ASCO in Action podcast to talk about it. I encourage our listeners, again, to read the full report by visiting asco.org/cca.
Dr. Richard Schilsky: Thanks, Cliff. This is really a fun project for me to work on every year with wonderful ASCO volunteers, and I hope our members will enjoy reviewing all the advances summarized in the report this year.
Dr. Clifford Hudis: For those of you listening, if you enjoyed what you heard today, please don't forget to give us a rating or a review on Apple Podcast 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.
Disclosure: Dr. Schilsky reports serving on the board of directors for the Reagan-Udall Foundation for FDA and research grants to ASCO in support of a clinical trial from the following companies: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Meyers Squibb. Genentech, Lilly, Merck, and Pfizer.