What’s on the Horizon for RCC Treatment and Care?

A roundtable discussion, moderated by Brian Rini, MD, discussed the latest data from the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024 in clear and non-clear cell RCC. Dr. Rini was joined by David McDermott, MD; Elizabeth Plimack, MD; and Martin Voss, MD.

In the final segment of the roundtable series, the panel shares their outlook on the near future for renal cell carcinoma research, treatment, and care.

Hear more from this series.

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Dr. Rini: Any other exciting data at ASCO [GU], subcutaneous nivolumab, any of the rapid orals that caught your attention in kidney cancer? Martin, we’ll start with you. Or if nothing, then maybe what’s the biggest either dataset or concept that you’re thinking about moving forward in the next 6 to 12 months that you think might impact clinical care?

Dr. Voss: Yeah. I do think we saw updated data on LITESPARK-005, so the quality of life data, I think is in keeping with what’s been reported before. It’s nice to see more details and reaffirm that that’s a very tolerable regimen. I think that makes me excited about the various belzutifan-based combinations coming out both in pretreated patients, there’s a phase 3 that’s fully accrued with a combination compared to single agent cabozantinib and then upfront, the LITESPARK-012 study, which is also fully accrued. We’ll read out at some point, that looks into triplet therapy now with a more tolerable oral agent than what we saw on COSMIC. I think that’s what I’m most excited about in terms of big things coming.

Dr. Rini: Sounds good. Betsy, what do you think?

Dr. Plimack: Yeah. I think I love the long-term follow-up. I think the devil is in the details and we should continue to seek those. I would love to see, as mentioned, treatment-free survival data for the TKI/IO combos, but first we have to have the courage to stop the TKI, either within the study or outside, and I’m not sure enough people do for us to really get at that answer. I also remain excited about belzutifan. I think the phase 3, while positive, we thought the delta would be a little bit better compared to everolimus. There are reasons for that we don’t have to go into. But yeah, where is that best positioned? It’s so well-tolerated. It can lead to durable long-term responses. Who are those patients and what sorts of combinations do we need to prove that? Then let’s learn going forward from what we didn’t do in the older studies, which is let’s have the courage to stop treatment in deep responders and see and measure what happens.

Dr. Rini: Great. David, final word on this.

Dr. McDermott: I agree with my colleagues. I’m all for more treatment-free survival research that Betsy wants us to do because it measures both the good and the durable bad of IO toxicity, which certainly is real. I think building on what they said about HIF inhibition, it is easier to take than many of our old therapies. I think if you had compared quality of life of belzutifan versus a VEGF TKI, you would’ve seen even bigger differences. As Betsy said, those differences with everolimus were real but not awesome.

I think it would be a bigger difference if you were comparing it to some of the TKIs we use. But that just says we should try to move HIF inhibition up more as a single agent, which Martin mentioned some of those trials which are interesting in combination and could change standard of care. But it doesn’t mean we shouldn’t try to treat some patients with single-agent HIF earlier in their course as opposed to third and fourth line. Maybe we can do that with selection; maybe we can do that with these other HIF inhibitors that are in clinical testing that we should be able to see more data on in the next year or 2.

Dr. Rini: Yeah. I would just add I agree with all of that. What we really want to see, and I don’t know that I saw much at ASCO GU, is just novel mechanisms, right? It’s HIF/VEGF and it’s IO, which is great and we talked about it for 45 minutes, but truly novel, different mechanisms, metabolic pathways, whatever that might be. In walking around the posters, I didn’t see a lot of that unless I missed something. I think there’s definitely a subset of patients who are not responding to either and blows through either. We really need to understand that biology and have druggable targets, and I’m not sure we’re quite there.

Dr. McDermott: Right. As we move all these therapies up, you get to the end of the line of therapies sooner, so we need novel therapies. That’s for sure.

Dr. Rini: Agreed. Just want to thank Drs. Plimack, McDermott, and Voss. It was a great conversation, lots more to talk about, and appreciate everyone joining us for this ASCO [GU] Virtual Roundtable.