ASCO GU Data Updates in Frontline Kidney Cancer: Was Anything Practice Changing?

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 first segment of the roundtable series, Dr. Plimack shared her approach to frontline clear cell kidney cancer treatment selection and commented on long-term follow-up data presented at ASCO GU.

Watch the next segment in this series.

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Dr. Rini: Why don’t we start with frontline clear cell kidney cancer. There were a few updates at ASCO GU. There was, I believe, an 8-year ipilimumab/nivolumab update, impressively long data. There was approximately, 4- or 5-year update of the cabozantinib/nivolumab data and then some subset data from lenvatinib/pembrolizumab that was presented. Betsy, I’ll call on you first if you don’t mind. We’ve talked a lot in this and many other settings about frontline kidney cancer and IO/TKI versus IO/IO, but maybe if you could just think about if the recent data impacted you, how it impacted you, and where are you in early 2024 in that debate and in your practice?

Dr. Plimack: I still find it a fascinating topic, frontline. I know we’ve seen now the data multiple times and we’re just watching long-term follow-up, but that is so critical to see how patients do long-term, because we designed these studies thinking that all patients would ultimately progress and pass away on these studies and they’re not yet. With ipilimumab/nivolumab at 8 years, we’re still seeing folks surviving, some not even progressed yet, and it looks like the other TKI/IO combos are going to follow suit based on where we are now at the 4- and 5-year follow-ups for these studies.

I’m excited about the data. I think every time a fresh cut comes out, I try to challenge my assumptions and my practice to see if anything changes. I will say so far, no changes to the way I approach, which is lenvatinib/pembrolizumab for poor and intermediate risk and axitinib/pembrolizumab for good risk. Again, looking for that early response rate so patients can be durable responders. I do want to see in the future, and this is a shout-out to David because he’s done this analysis for ipilimumab/nivolumab, but treatment-free survival for the TKI/IO combos, because the one drawback that we hear from clinicians about those combos is that we can never stop therapy. I’m not sure that’s true, but we have to ask the question.

Dr. Rini: Just maybe to summarize, so updates are good, right? We always want to see long-term data and patients want to know, “Doc, what’s going to happen to me over time?” They don’t just want 1-year data, they want multi-year data, appropriately. Nothing necessarily in the data presented at ASCO GU it sounds like that impacted your practice, is that correct?

Dr. Plimack: Correct, yeah.

Dr. Rini: I guess maybe the question is what kind of data would impact that practice for you? It doesn’t seem like the ipilimumab/nivolumab data is going to change. It’s been remarkably consistent I guess now for 8 years, so probably year 9 and 10 won’t bring us a whole lot of changes, but is there something for future data where you’d say, boy, now I’m going to do something different?

Dr. Plimack: Yeah. I think what I’d like to see in future data, what would change my practice, is really patients who we are curing, meaning they die of something other than kidney cancer. We never thought we’d have the opportunity to explore this. We have assumed that deaths on any clinical trial are deaths from the cancer that we’re studying, but I think that might not be true for ipilimumab/nivolumab. While we have these overall survival curves, the question is, some patients out 8-plus years will pass away. If that’s happening and they’re dying of other causes, that’s a win, not a loss.

If we could look at that and really see that that’s happening, that could change my practice. I would also need to know that that’s not true for the TKI/IO combos. That would need to be shown also, and those studies are quite a bit further behind in doing that because we do sacrifice that upfront response rate with ipilimumab/nivolumab over a TKI/IO. I think there are opportunities for very long-term data cuts if we look at the right things to actually inform and change how we practice now.

Dr. Rini: I don’t think, you all can correct me if I’m wrong, I don’t think we’ve seen such data about, I don’t know, non-renal cancer deaths in any sort of granular form. I think I’ve seen some disease-specific survival curve somewhere, I can’t quite remember, but I’m not sure we’ve seen that sort of granular data, correct?

Dr. Plimack: Not yet. We should keep asking for it.