The Latest Data on IO/TKI Versus IO/IO in Frontline RCC

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 next segment of the roundtable series, Dr. McDermott advocates for immune therapy in frontline RCC care and discusses how he handles remission rate conversations with patients.

Watch the next segment in this series.

—

Dr. Rini: David, since ipilimumab/nivolumab was brought up, you’re our ipilimumab/nivolumab representative on this panel and always, so what do you think? Obviously, you’ve advocated ipilimumab/nivolumab as an approach for most patients including favorable risk. Anything about the updated data that was presented or any of the ASCO GU data that you found interesting or impacted your practice?

Dr. McDermott: Well, just to be clear, what I would like to be known as an advocate for immune therapy as early in the process as possible in the right patients, not as the ipilimumab/nivolumab rep, if possible. I often get asked to defend that, which is fine. Because I think building up pure IO therapies are one way toward durable benefit, as Betsy said. It’s also a way toward remission. Meaning there are some patients, they’re a minority of the patients, who get a deep response and then can come off treatment. Sometimes they come off because the response is impressive. A lot of times they come off because of toxicity, but the bottom line is they can stay in response, and I think that’s one of the things, probably the most impressive thing, about the ipilimumab/nivolumab curves over time is if you’re fortunate enough to be a responder, those responses can be very durable and patients can be alive, and as Betsy mentioned, in treatment-free survival, which is really our patient’s goal, is not just to live longer, but ideally they’re living in remission, potentially cured.

I think proving cure is a little hard because you need a lot of follow-up and the great news is we’re getting long-term outcomes. The bad news is our trials are not well-designed to collect long-term data. Beyond 5 years, our data becomes a little fuzzy on some of those issues, but it’s so worth looking at. One of the things that Betsy mentioned that actually has been looked at is treatment-free survival with the VEGF PD-1 combinations. The FDA actually combined all the 3 major trials into 1 dataset, several thousand patients. They presented it at ASCO last year. Unfortunately, it didn’t even make it as a poster, which is kind of rough grading on the committee’s part, but it’s going to be a publication.

Essentially, what the abstract showed was there was no significant improvement in treatment-free survival for those combos, which means you can still get durable benefit, but most of the patients getting that benefit were still on 1 of the drugs. The good news is long-term outcomes are possible. That should be our goal. If we can get beyond long-term outcomes to remission, that should also be something we push for. I think things that build on the immune response to the tumor are one way to get us there. Those are the kinds of things we learned at this meeting, which is nice.

Dr. Rini: I have a comment and a question for you. Comment is unfortunately, the way the IO/TKI regimens were designed, that treatment-free survival is going to be driven by the TKI, because we didn’t stop it. Most people weren’t really stopping for toxicity. They’re probably dose reducing and such. I think it complicates that interpretation. My question for you is a patient walks into your office, whatever characteristics you want, intermediate risk, sarcomatoid, whatever characteristics you want. You’re going to give them ipilimumab/nivolumab. When they say, hey doc, what’s my chance of being cured with this? You have to give them a number, I’m going to force you to give them a number. They’re not leaving your office. Give me an idea. Is it 2%, 10%, 25%? Is it 50%? Give me an idea of what are my chances of being alive, controlled disease, in 5 to 10 years from now?

Dr. McDermott: I personally don’t use the C word much in clinic. I know that’s what patients want to hear. The reason I don’t is experience. I’ve been doing this for 25 years, which is a ridiculously long time to be doing this. I have had patients who got, for example, got IL-2 18 years ago and then came out of remission. If you tell that person they were cured, it’s a little bit… You look like a buffoon.

Dr. Rini: Okay. Let’s put aside that word.

Dr. McDermott: Remission is the word, and I think the right word is somewhere between…

Dr. Rini: Fine. Remission. What are my chances of being in remission?

Dr. McDermott: I think it’s about 15% or 20% durable, somewhere in there. Some say maybe a little north of 20%. It’s somewhere around that range. It’s obviously the minority of patients, but it’s a real number.

Dr. Rini: You get that from, I think the latest PFS curve for ipilimumab/nivolumab, I think the number to the farthest right was about 25%, right? On the landmark PFS at I don’t know if that was 8 years. I’m trying to remember the curve, right?

Dr. McDermott: Yeah, that’s for intermediate and poor. It’s 17% for favorable. One of the things that I think we learned from this meeting again is we should ditch the whole subset thing and just look at intent to treat, but I think that’s about what you get.

Dr. Rini: I’m going to put that aside for a second, but that’s what you’re saying is that alive and progression free is about 20% if you look at the ITT?

Dr. McDermott: Correct.