Panel Discusses the Value of Immunotherapy in Frontline RCC

A roundtable discussion, moderated by Brian Rini, MD, addressed considerations for clear versus nonclear cell kidney cancer, as well as recent data from ESMO 2023. Dr. Rini was joined by Tian Zhang, MD; David McDermott, MD; and Hans Hammers, MD.

In the next segment of the roundtable series, the panel addresses the place for immune monotherapy, as well as takeaways from trials like PDIGREE, PROBE, COSMIC-313, and more.

Watch the next segment in this series.

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Dr. Rini: Let me ask 1 final question about frontline regimens. We haven’t seen the results of [CheckMate] 8Y8, which is ipilimumab/nivolumab versus nivolumab. Maybe a 2-sided question: Is there anybody that you use immune monotherapy in, and do you really believe ipilimumab is adding anything?

Dr. Zhang: Oh, that’s interesting. I don’t give PD-1 monotherapy. I heard David does, so I’d be curious to hear about that. To be honest, I do think trials are important. We’d be remiss in the frontline setting not to talk about PDIGREE and PROBE. There are cooperative group trials still ongoing now where adaptive design, like Hans’ approach, ipilimumab/nivolumab first, then followed by an early edition of cabozantinib/nivolumab for PDIGREE. PROBE is the question of consolidated nephrectomy 3 months into immunotherapy. I think that there’s still reasonable options. If I use CTLA-4 blockade, to your initial question, I try to use it early. We’ve seen from multiple trials that using salvage ipilimumab is not effective. But I’d be curious to hear about PD-1 monotherapy.

Dr. McDermott: You asked 2 questions.

Dr. Rini: I did.

Dr. McDermott: I’m going to wait to answer Tian’s question, which I don’t know, that’s separate, I think.

Dr. Rini: Yeah, they’re separate. Do you use immune monotherapy in any patients?

Dr. McDermott: Yes. I have a discussion with them about risk, and as Hans was just saying it’s double the risk of severe toxicity. If they go like this, then we give them PD-1 alone. There’s a percentage of patients, they tend to be older, tend to be sicker, less motivated. The data with single agent PD-1, admittedly, at very selected centers is pretty good. Both in KEYNOTE-427 and the HCRN trial is ridiculously good data. There’s that. It’s obviously not phase 3 data, and it’s certainly more tolerable. Now whether [CheckMate] 8Y8 is going to be positive or not is a totally different question. We’ve been waiting, it seems like, a decade for that trial to read out. To me, The trial is underpowered, it’s small, it may not have the right endpoint. We’ll see. Will it be practice-changing or not in the United States or Europe? It’s possible. But either way, to me it’s about building on IO [immunotherapy] backbones. Even if we use less CTLA-4 in the future, I’m hoping to build on PD-1 plus the next exciting targeted immune therapy. That’s what I’m hoping for and hoping those are the controls. To me, the best controls for future studies are ones that have IO in the control arm.

Dr. Rini: Yeah, I agree. Hans, last word on this.

Dr. Hammers: Totally agree with David that [CheckMate] 8Y8 I don’t think is going to be a defining study to tell us where ipilimumab stands. I think we need to look at the aggregate of data. It’s an underpowered trial, and I think that we all know that ipilimumab has single-agent activity, 10%, 15%, and that’s what you see across all these different trials. It started, for example, with PD-1 and then did some salvage with PD-1 CTLA-4. I think the trial to watch quite frankly is the control arm on COSMIC-313. I think that’s the biggest contribution to the field from that study. I don’t think the triplet should be approved, but I think the control arm will actually show modern-day use of PD-1  CTLA-4, and the curves look pretty good. We have to see what the long-term follow-up is. I think there’s going to be a real value to the community.

Dr. Rini: There may be some better follow up and less censoring on that trial.

Dr. Hammers: …Better follow up, less censoring.

Dr. Rini: To David’s point about patients…

Dr. Hammers: More modern use of TKI [tyrosine kinase inhibitors] switching over to TKIs if needed be. That’s going to be actually a really good data set.