Selecting Treatment for Advanced RCC in Second Line and Beyond


Panelists identify second-line treatment options they would consider in advanced clear cell RCC if a patient progresses following first-line therapy.


Brian Rini, MD: I’ve got 2 other big topics to tack on in our last 5 or so minutes. Let’s say you have a patient who got adjuvant pembrolizumab and progresses. And I’m starting to see these patients in my clinic, as I’m sure you are. How are you approaching those patients? And let’s take right now the patient who would walk in the door. I saw a patient who got 6 months of adjuvant pembrolizumab, got the scan for routine restaging, and had progression. So patients are progressing on therapy. I’ve had patients progress years later, which wouldn’t be possible now. Let’s put that aside. But a patient progresses on pembrolizumab and tolerated it. Let’s say they received 6 months of treatment, for the sake of argument, and then they walk in and say, “Hey doctor, what should I do now?” Hans, why don’t you start.

Hans Hammers, MD, PhD: That’s complicated. I think it depends on the tumor burden at the time, how it progresses. If it’s just 1 or 2 nodules, it’s a different scenario than somebody who was not—

Brian Rini, MD: It’s moderate. It’s not addressable by local treatment. Let’s say that.

Hans Hammers, MD, PhD: But if it’s smaller…I understand we talked about how ipilimumab works best, I agree with you, early on. But, for example, we had both trials open, and I had a patient progress in the atezolizumab adjuvant trial who was exposed to atezolizumab. I treated them with nivolumab-ipilimumab, and he had, essentially, a very deep response. It’s now been going on for years. So it’s not that it cannot work. I think it depends on in which patient is a 10%, 15% response rate reasonable to consider up front, or not. It will not be many patients, I totally agree with you. A TKI [tyrosine kinase inhibitor] will be important. We’re now learning how important it is, or not, to continue on immune checkpoint inhibition. Some of the CONTACT-03 studies, TiNivo-2, etc., will be important to inform us in that regard. And then for some patients where you want to kind of give both, control the lesions, and then maybe alter CTLA-4 without too much risk, you can then consider triple therapy. So it really depends on that scenario.

Brian Rini, MD: Let’s save the triplet discussion.

Sumanta Pal, MD, FASCO: Brian, we should have started with these questions. This is good.

Brian Rini, MD: I hear you saying there may be a role for salvage ipilimumab. Let’s call it salvage ipilimumab-nivolumab. In those patients [INAUDIBLE], but they certainly haven’t been exposed to ipilimumab, so that’s reasonable. But would you agree that probably single-agent TKI is the standard in those patients? It’s a very unsatisfying standard, I’ll give you that.

Hans Hammers, MD, PhD: Are you asking me?

Brian Rini, MD: Yes.

Hans Hammers, MD, PhD: I agree. It’s unsatisfying. On the other hand, I don’t routinely continue an immune checkpoint if somebody progresses on it. So if somebody progresses on nivolumab-ipilimumab, I don’t continue on nivolumab, I don’t continue pembrolizumab. It makes no sense. So those patients will be in the same group, unfortunately.

Brian Rini, MD: Monty, what do you think? How are you treating these adjuvant pembrolizumab failures?

Sumanta Pal, MD, FASCO: It’s such a tough question, Brian. But I do think there’s sort of a red zone and a green zone for further immunotherapy. That red zone for me is kind of like the scenario that you’re stating, where that patient is on adjuvant I/O [immuno-oncology] and they progress during that span of time. Hans, I may be looking at this way overly simplistically, but I view that as being a patient that has sort of exhausted their benefit from I/O. Despite examples like the one you’ve given, if your patient is on adjuvant atezolizumab followed by nivolumab-ipilimumab, I’d probably go with that sort of unsatisfying strategy that Brian suggested of using a TKI alone. I’d probably follow it with TKI monotherapy. The green zone for me, on the other hand, where I’d want to rechallenge that patient, that you kind of alluded to, Brian, where they finish up adjuvant I/O, then a year or 2 passes, then go ahead and start on double. The gray zone is everything in between. I have no idea what we should be doing there.

Hans Hammers, MD, PhD: Totally.

Brian Rini, MD: I was saying to a patient the other day that it’s a totally data-free zone right now, and nobody really knows what to do. I’ve been pretty much recommending single agent TKI, but I also do talk about ipilimumab-nivolumab. I think if I had a younger, healthier patient, I might lean toward that, but we’ll see. I think some of the ongoing trials like TiNivo-3 do allow patients who simply failed adjuvant pembrolizumab. Is that right, Monty?

Sumanta Pal, MD, FASCO: Yes.

Brian Rini, MD: So, we’ll start to see trials and data that actually inform this decision, but it’s clearly going to be an emerging patient population.

Transcript edited for clarity.

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