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Rationale Behind Discontinuing IO Therapy in Clear Cell RCC
Focused discussion on the rationale behind discontinuing (or continuing) immunotherapy for patients with advanced clear cell renal cell carcinoma.
Transcript:
Brian I. Rini, MD:We’re going to move on to the second-line therapy discussion. We’re going to talk about the CONTACT-03 trial [NCT04338269]. I think we’ll stick with the case since we have it in front of us. So I treated this patient with axitinib/pembrolizumab, had a nice PR [partial response] on the initial scans, maintained maybe some axitinib dose adjustments, etc. Actually got to the 2-year mark as [approximately 25%] of patients in KEYNOTE-426 [trial] did. I discontinued the pembrolizumab, which I do because that’s the way KEYNOTE-426 did it. Does anybody not discontinue IO [immuno-oncology] at 2 years? All the trials that have showed a survival benefit have discontinued at 2 years.
Eric Jonasch, MD: I tend to continue it.
Brian I. Rini, MD:I continue.
Bruno R. Bastos, MD: I tend to continue it too. I’ve seen many cases in boards of patients recurring after the discontinuation.
Brian I. Rini, MD:They’ve continued TKI [tyrosine kinase inhibitor] and progressed?
Bruno R. Bastos, MD:: Progressed, yes.
Brian I. Rini, MD:OK. Is that why you do it?
Eric Jonasch, MD: I do it because there’s no mechanistic rationale for discontinuing it…. Part of the reason why we’re perhaps seeing a collapse in the curves in the IO/TKI PFS [progression-free survival] is because of the fact that you’re discontinuing therapy. So it’s an unprovable statement, but generally speaking, I will continue it unless, of course, there’s toxicity. A lot of times there are patients who develop toxicity, and that will define what you give for how long.
Brian I. Rini, MD:I’ll disagree with you a little bit. I don’t think there’s been collapse of the overall survival curves. If you look at that [more complete] analysis, it’s not that patients are progressing and dying. That’s not what’s driving those curves coming together. It’s the [patients taking sunitinib] being rescued. So that was my first thought: “Oh boy, we had better not stop pembrolizumab at 2 years.” Again, the data are not perfect, and we haven’t looked into it completely. I don’t know the clear part of this, but I don’t think that it’s stopping pembrolizumab. I would argue mechanistically, that’s what immune therapy is supposed to do, right? You’re supposed to give it up front, generate an immune response, and then stop.
Bruno R. Bastos, MD: If you have a complete response perhaps it makes more sense to me….. In this case it’s just pembrolizumab or PD-1. I would not stop.
Stephanie A. Berg, DO: I’ll agree with you. I’ll say that ipilimumab is immune therapy that you stop after 4 cycles. We’re trusting that that is causing all these long-term benefits even though it stopped years ago. So I think the idea that you can stop IO does make mechanistic sense, at least in my mind. I will say I have some really lovely treatment-free survival scenarios with IO/TKI, where I’ve stopped both and they’re getting scans and they’re doing well. So most people have those stories related to their [patients taking] ipilimumab/nivolumab. But perhaps because I practice, I have a nice collection of those [instances].
Bruno R. Bastos, MD: If the patient had a complete response, it would make sense to consider discontinuing, but if the patient still has disease on scans, like this patient who had a partial response not a CR [complete response], I will not stop it.
Brian I. Rini, MD:…. We’re not going to resolve this in this session, but it sounds as though there’s uncertainty…. I think there’s real uncertainty about continuing, and it’s just the way it was done in the trial.
Stephanie A. Berg, DO: I mean, all trials nowadays are stopping. Is there a trial that’s actually in kidney cancer that’s making…
Brian I. Rini, MD:Actually, avelumab did not stop.
Stephanie A. Berg, DO: Nivolumab did not. None of the nivolumab studies stopped. I don’t know about the…
Brian I. Rini, MD:And cabozantinib [plus] nivolumab did.
Stephanie A. Berg, DO: Cabozantinib/nivolumab stopped for the IO combination, the combination studies.
Brian I. Rini, MD:It’s a mixed bag. I didn’t want to go too far down that rabbit hole.
Transcript edited for clarity.
