Evolving Treatment Landscape of RCC: Future Directions in Care


Closing out their program on renal cell carcinoma management, key opinion leaders share closing thoughts on emerging therapies and how the field is evolving.


Brian I. Rini, MD, FASCO: We just have a few minutes left. I’m going to ask each of you to comment on what [you are] most excited about in advanced kidney cancer, say, over the next 2, 3, 5 years? What do you think [is] going to have the biggest impact? It can be a mechanism or an approach; it can be a regimen. It can be triplets in general. All of these...[are] very broad based. But...in in 30 seconds, what do you think, if anything, is really going to...change the fundamental approach and improve outcomes for patients? Tough question, so Bob, I’ll start with you.

Robert J. Motzer, MD: Well, we’re actually [in] a little bit of a pause with regard to therapeutics in terms of a step moving forward. So...I was a little bit disappointed by the COSMIC-313 data. We’ll have to see what the survival benefit is, if there is one, and also the Merck triplet data. But other than that...it’s really...looking at novel approaches, cellular therapy, [and] seeing if we can define new mechanisms. And...there should be a large emphasis on better understanding of the underlying biology so we can...accomplish those.

Brian I. Rini, MD, FASCO:Betsy, what do you think?

Elizabeth R. Plimack, MD, MS: Yeah, I agree with that.... Looking at these data…[I think it] is important to step back and reflect on how much progress we have made in a relatively short period of time that an overall survival that was less than 2 years when we started this journey with immunotherapy is now much longer for a lot of our patients. So that’s great. I would say we didn’t touch upon belzutifan in this session. I’m excited about that drug and more than in combination, I’m excited to see how it extends survival and benefit as a sequential single agent. And when we look to the future, in addition to, of course, looking for new therapies, which we desperately need in this population...we should also look to how to wisely sequence things. It’s a very hard question to answer. I’m not sure it can be answered in a randomized trial, although PDIGREE [NCT03793166] is trying that. But...in some ways it’s a marathon, not a sprint now, and sequencing and being smarter about that could be a useful place to look.

Brian I. Rini, MD, FASCO: Thank you. Moshe, what do you think?

Moshe C. Ornstein, MD, MA: I’m excited about the novel agents that are being investigated as opposed to...another TKI [tyrosine kinase inhibitor] or another IO [immuno-oncology] or another combination of an IO TKI. And...what we saw at KCRS [Kidney Cancer Research Summit], for instance, is the LITESPARK-024 [trial (NCT05468697)], which was looking at belzutifan vs belzutifan plus a CDK4/6 inhibitor. Seeing what role...that might play in advanced kidney cancer, especially in the refractory setting based on some investigations in [William G. Kaelin Jr] Kaelin, [MD]’s lab. And then...although we’re not maybe overly enthusiastic about some of the other novel mechanisms, whether it is CAR-T [chimeric antigen receptor T-cell therapy] or whether it’s antibody-drug conjugates of anti-CD70...investigating the CD70 pathway, whether it’s with the CAR T cells, whether it’s antibody-drug conjugates—gives us another potential target. And also, potential novel mechanisms might not work for everyone. [It] might be finding the right subset, might be finding the right sequence or combination. But it’s nice to see these novel therapeutics [and] novel targets being investigated.

Brian I. Rini, MD, FASCO: And I might just add...ctDNA [circulating tumor DNA] , which is being investigated in a lot of other diseases, bladder, which we all see, hopefully gets developed in RCC [renal cell carcinoma], maybe some novel imaging...like PSMA [prostate-specific membrane antigen]/PET in prostate cancer, which has revolutionized that disease. So...not even new drugs, which I totally agree are important in mechanisms, but new tools to better take care of patients, to better find oligometastases that can undergo SBRT [stereotactic body radiotherapy], etc. So hopefully, all of that continues to develop over the years. I’d like to thank all of you—Drs Ornstein, Plimack, and Motzer—for a great discussion and review of recent data from some major kidney cancer conferences and ASCO [American Society of Clinical Oncology]. Thanks to the audience for joining us today. Hopefully you found it insightful and helpful in taking care of patients. And as we close, let’s take a quick look at some additional insights and perspectives about these data updates from experts in the field that they’re sharing on [X, formerly known as Twitter]. Thank you.

Transcript is AI-generated and edited for clarity and readability.

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