The panel explores unmet needs in aRCC treatment and shares expectations for changes and advances in the landscape in the near future.
Dr. Robert Motzer: I think we certainly have made really significant gains in treatment for advanced RCC and it's all really an entire different story than years back now with the TKI-IO combinations and IO-IO and so forth. But I think people are asking what's next? And Betsy, what do you see as in terms of a vision moving forward for advanced RCC in terms of both unmet need and that you'd like to see addressed? As well as is there any particular treatments or what have you that are on your radar screen to keep an eye on for the next five to 10 years?
Dr. Elizabeth Plimack: Sure. So I'll put a plug in just for a space that I think we need to be active in. So we are used to writing clinical trials that limit to one, two, three prior therapies, that's irrelevant to the health of the patient and their fitness to try a novel agent. And so I'm really hoping to see more end-line trials. Our patients are living longer and better. We sometimes are trying multiple TKIs, that's not really multiple lines of therapy, it's one type of treatment, but it's excluding a lot of our patients from the trials the way they're written that are jockeying for like frontline, second line, or third line. So that's where I want to see it. I think if there's activity of a novel agent in that space, we're going to see it. And the drug I'm most excited about is the one where we tested it that way, which is belzutifan, which was tested in an endline trial, showed really cool results in a lot of our patients. Those long-term have born out and now it's the randomized trial data. We're awaiting it, hoping for FDA approval and clear-cell renal cell. But having given it on clinical trials here to many, many patients, I usually seek a letter of medical necessity to try to get it for folks once they've exhausted IO, TKI, and everolimus, wherever you fit that in.
Dr. Brian Rini: Just to say a few things, I think we're going to develop better patient classification. I think IMDC is great, but we've painted ourselves into a corner with those clinical features. And I hope we have therapy based on biology, not just clinical features. I'd love to see development of more sensitive imaging tools like they've done in prostate with PSMA PET, which is totally revolutionized, that disease space. And if we had that in kidney cancer, we could do more metastasis directed therapy. Also development of ctDNA to measure, which could maybe help us limit duration of therapy if patients turn ctDNA negative or functional imaging cold or something like that. We don't have much of that in our CC. I think we just need new categories of drugs. We have enough PD-1 inhibitors and TKIs frankly, like we need therapy against the myeloid compartment and metabolomics, whatever your thing is, we just need novel mechanisms. Belzutifan I'd put in there, but it's cousin of TKI, so it's novel but it's not. And we need upfront immune-based regimens that shrink tumors better. The knock on Ipi-Nivo is not just toxicity, but that primary PD rate we talked about, the limited response rate. And we need other novel checkpoints or novel immune mechanism drugs to develop perhaps doublets and triplets. I'd love to see TKI-free regimens developed. I love TKI as much as anybody, but I'd love to see them go away entirely where we just don't need them. We control disease via other means, or we limit their duration or we replace them with HIF inhibitors, whatever the permutation is. I'm hoping, I guess, that we develop those drugs moving forward.
Dr. Robert Motzer: Well, this has been an extremely informative discussion. And I'd like to thank both Betsy Plimack and Brian Rini for this insightful discussion. And thank you to our audience for watching this targeted oncology discussion. We hope you found this discussion to be informative and valuable to the treatment of your patients with advanced renal cell carcinoma.