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Feb 21, 2020

Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll. The Genitourinary Cancer Symposium hosted by ASCO in San Francisco revealed some significant clinical developments, and here to discuss key takeaways from the meeting is Dr. Karen Knudsen, program chair of the symposium. Dr. Knudsen is the enterprise director of the NCI-designated Sidney Kimmel Cancer Center at Jefferson at Thomas Jefferson University and Executive Vice President of oncology services at Jefferson Health. Dr. Knudsen, welcome to the Daily News Podcast.

Dr. Knudsen: Thank you so much for having me. It's really a pleasure to get a chance to discuss all of the things that were revealed at the 2020 ASCO GU.

ASCO Daily News: Dr. Knudsen, do you have any conflicts of interest that you'd like to disclose, which are relevant to our conversation?

Dr. Knudsen: If I do have conflicts of interest, I don't think they're relevant for the conversation. But I like to disclose them anyway. As the cancer center director, it's something all of us are trying to pay more attention to. So I do have advisory and consultant positions with CellCentric and Genentech. I've had ad hoc advisory board positions in the last two years with Sanofi, Janssen, Novartis, and Celgene, and research support from CellCentric and Celgene.

ASCO Daily News: All right, thanks Dr. Knudsen. Well, the Genitourinary Cancer Symposium showcased a lot of interesting presentations and insights on topics across GU malignancies. So what are your key takeaways from the meeting?

Dr. Knudsen: So this was really an exciting meeting for us, and the way that we put together the program was aligned to our theme, which is, in pursuit of patient-centered care. And the program committee and steering committee really worked together to try to decide how the 2020 program should come about. And it was to take all of the things that were and are fantastic about ASCO to you and take it even further in a couple of different directions.

Dr. Knudsen: One is to incorporate really the latest science, the latest evidence for some of the new agents and new interventions that we're seeing develop for GU malignancies, and also look to the future of things that are coming. The second was an emphasis on multidisciplinary teams, so effective integration of urology, medical oncology, and radiation oncology as related to GU cancers, but also the translational science behind the new findings and seeing those come together.

Dr. Knudsen:  And then the last was a focus on quality of life. As we've had all these new interagents and new interventions introduced over the last few years in the GU malignancy field, we felt it was really important for us to ensure that we're addressing impact on quality of life, including but not limited to financial toxicity throughout the meeting. And I think those elements were really achieved by dissection of the program, but also, we've heard just tremendously positive feedback from attendees about that additional incorporation and thoughtfulness within the meeting.

Dr. Knudsen: So you know, kind of keeping that in mind, I think that some of the key takeaways are that the pace of our field is really moving quickly with regard to innovative imaging, combinations, especially novel combinations using immunotherapy as a backbone. We heard about new endpoints, PSS2, new biomarkers, and incorporation of targeted agents. So across all of the GU malignancies, there was this feeling that the pace has really accelerated for new opportunities for detection and intervention.

Dr. Knudsen:  In order to also really address what some of those new possibilities are, we had something quite different this year. We had the FDA with us in a, quote unquote, meet the regulators session to talk about some of these new technologies, new endpoints. And they actually walked us through a previous example of something that had come to light in the last few years in the GU field, which is incorporating the MSF or metastasis-free survival endpoint into GU malignancy trials. And that was a really important one.

Dr. Knudsen: We also had some great reminders about how to ensure that our science and our clinical trials are tending to both statistical and clinical relevance. Fantastic statistical talk from Dr. Sides, who walked us through some of the ways that we can sharpen our focus on ensuring that we're drawing the right conclusions from the trials and the preclinical studies that we cover.

Dr. Knudsen: And attendant to the theme of the meeting, we had a really fantastic keynote lecture from Dr. Dave Penson at Vanderbilt on financial toxicity and the impact on quality of life, as well as other endpoints, including patient-related outcomes and the overall outcomes from new interventions. He educated us about coping behaviors that patients engage in that may shift their compliance for cancer care and certainly, as may be related to other adverse events, and really shared with us some striking data about the number of patients that may be depleting their total net worth after a cancer diagnosis. So that part was really a call to arms to have all of us help attend to educating the patient as much as possible about financial ramifications, as well as other ramifications of therapies as they're introduced. So really, fantastic science, moving very quickly, and now we're ready to address some of the other ramifications of the newer interventions that we're introducing.

ASCO Daily News: Speaking of new interventions, were there advances reported that would likely support new standards of care moving forward?

Dr. Knudsen: There were. I think there-- you know, there were a number of advances that we're going to want to really track carefully over this next year. So advances in imaging were prominently discussed at the meeting-- when to use next generation imaging and taking into account disease state and clinical scenarios. Advances in standard of care are likely to also include-- we heard a lot about this at the meeting-- an increased incorporation of genetics, including both somatic and germline alteration.

Dr. Knudsen: Dr. Castro gave us a really fantastic talk about the importance of profiling both somatic and germline alterations in patients, especially patients with advanced disease or who are at risk for aggressive disease, and showed us some compelling data about the limitations and ramifications of only looking at one, either somatic or germline. And that's probably not serving the patient as well as we could-- and gave us some very strong examples, especially with regard to DNA repair mutations, about how to incorporate this and to tailor therapy.

Dr. Knudsen: I think that we'll see some changes coming in the future with regard to gene signatures and biomarkers. For example, even just in the prostate space, we heard about a 22 gene signature from Dr. Feng, which may predict who is going to need more aggressive care, as well as from Dr. Klotz with regard to non-coding RNAs and their ability to predict prostate cancer behavior.

Dr. Knudsen: So this is actually a really interesting session, because we got into the dynamics of how we actually bring this to a change to [INAUDIBLE] where one of these signatures become standard of care, given the long-term follow-up that's really required to understand how these signatures inform prostate cancer behavior. So there was actually quite some healthy debate on that within the ASCO GU meeting.

Dr. Knudsen: More forward thinking to later on was with some discussions with Dr. Beltran on epigenetics and how that may additionally influence our ability to predict behavior. But I think what I would say is probably the third and really interesting advance that we heard about at this meeting was our ability to use liquid biopsy and to have cell-free DNA or circulating tumor DNA inform the mechanisms of resistance that may be emerging in a particular tumor, and how we may treat that patient by anticipating and forwarding resistance. So a lot of really fantastic talks incorporated ctDNA into their discussions. Dr. Wyatt really stands out there in one of his discussions about the limitations of using circulating tumor DNA, but how promising this is with regard to giving concordance with what tumor lesions actually look like. So these are some technologies that are not quite ready yet to be incorporated as standard of care, but it's coming quickly.

Dr. Knudsen: The future is really near, and so those are, I'd say, were some of the forward-thinking things that we really discussed, which, of course, complemented the exciting trial data that we saw, things that have been reported out and are likely to give new approvals and new interventions for GU malignancies in the near term.

ASCO Daily News: You spoke about the prostate space a few moments ago. So I'm wondering, did any GU fields stand out more than others at this meeting?

Dr. Knudsen: You know, I think each of the fields have had significant progress, as evidenced by some of the clinical trials that we heard about. So for example, in the clear cell renal carcinoma space, there was a lot of excitement over Dr. Choueiri's talk looking at a new target. So there was a Phase 1/2 trial for a first in class agent that's targeting a protein called HIF-2 alpha. And utilization of this oral HIF-2 alpha inhibitor and advanced clear cell renal carcinoma.

Dr. Knudsen: So in this particular study, this new agent and the idea of targeting HIF-2 alpha actually emanated from what was the basis of the Nobel Prize in this last year with regard to understanding the factors that drive hypoxia and that are so important in this disease. And what was really remarkable about that Phase 1/2 trial is that there were objective responses seen in all of the different risk categories. So of course, the favorable category, but also the intermediate and poor risk category patients benefited from this agent.

Dr. Knudsen: And so this is really, I think, one to watch. There's a large Phase 3 trial, as we understand it, on the way for this agent. So you know, clear cell-- that was just one of the things that we talked about. In the bladder cancer space, there was the NEOBLADE study, which is a neoadjuvant chemotherapy study, which was really interesting and was the basis of a lot of discussion as well, because the primary endpoint may not have actually achieved the benefit, which is a path CR. But there was improved PSS and overall survival as well in those patients. So that's also something really for us to watch and gives us new thoughts about what neoadjuvant chemotherapy might look like in bladder cancer.

Dr. Knudsen: Another trial I think that was really interesting was the STOMP trial from Dr. Ost. So the primary endpoint for this study was something we don't always think about, which is androgen deprivation therapy free survival. That was really what was being tracked. And this is an interesting trial design. It wasn't designed to actually change practice, but to lay the foundation for a large Phase 3. And really, the question there for which the evidence looks quite interesting is, does metastasis direct to therapy improve this endpoint? Does ADT free survival? So I think that's one that was very forward-thinking type of strategy.

Dr. Knudsen: And then not to underserve radiation oncology, because it was also featured very prominently at the meeting, and there were a lot of exciting results in a number of different formats. But the chip trial reported this long-term follow-up of a Phase 3 study looking at conventional versus hyperfractionated high dose radiation therapy in prostate cancer. And this was really a really good news outcome in that type of fractionation strategy appears to continue to be effective in these patients that require long-term follow-up. And certainly, prostate cancer at this stage is that category. So large number of trials that are on the cusp of being practice changing, and I just got a chance to mention a few. But in my view, all of the GU malignancies had these kinds of breakthroughs throughout the meeting that were reported.

ASCO Daily News: That sounds very promising. And just finally, are there any other new agents in development or treatment approaches that really caught your attention and looked promising for the future?

Dr. Knudsen: Yeah, I think there are. So in the prostate cancer space, there was significant discussion-- And this, I'm sure, will continue into GU ASCO 2021-- about the treatment of oligometastases and that oligometastases are really not the same as low volume disease. And that is going to be increasingly important for us as a field to understand the biology of oligomets. This may cause us to really redefine, as we can now image oligometastases much better with PSMA, attached agents just to redefine the M0 state and reexamine our thoughts about the trials that have happened in the past, or, perhaps, these patients actually were not at the MDR stage.

Dr. Knudsen:  So that's one part of the oligometastases story. The other is, what is the impact of treating oligometastases? This is really where I think the field is moving. It's grappling with understanding that, and getting those trials to start to report out, I think, is going to be a really important thing for us to watch. In the muscle invasive bladder space, we talked and heard about the BLASST-1 trial from Dr. Gupta, which I think was also pretty exciting, exciting results with neoadjuvant, nivolumab, which [INAUDIBLE], and there was a report of the PCR in almost half of those patients. Think it was just under half of those patients-- really exciting.

Dr. Knudsen: SGFR3 got a lot of discussion as a new target for bladder cancer, and there's a preview of what a Phase 3 trial might look like. But then there are also some studies that were really back to basics. They were incredibly important. So Dr. Plimack from Fox Chase Cancer Center here in Philadelphia gave a spectacular talk on side effect management. And this was for frontline treatment of renal cell carcinoma.

Dr. Knudsen: And what she reminded us of is something incredibly important-- that strong side effects management, effective side effects management keeps patients on therapy and keeps them responding longer, and that we should not really undervalue this. It's something that's an important aspect of managing patients with advanced GU malignancies. And so as much as breakthroughs of new targets, new combinations, new ways to treat, new ways to image, but also, back to the patient centricity. Managing-- in this case, managing their side effects is a great way to get a better outcome. So important things to remember.

ASCO Daily News: Absolutely. Well, I want to thank you, Dr. Knudsen, for sharing these interesting highlights from the GU Cancer Symposium.

Dr. Knudsen: My pleasure.

ASCO Daily News: And to our listeners, thank you for tuning in to the ASCO Daily News Podcast. If you're enjoying the content, please rate and review us on Apple Podcasts.

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.