Initial Therapy for Advanced Renal Cell Carcinoma - Episode 8

How to Manage Borderline Intermediate-Risk RCC


Eric A. Jonasch, MD: What’s interesting about these various risk-stratifying algorithms is that we have 5 or 6 different features, and we then are bucketing people into good, intermediate, or poor risk. There’s obviously going to be a lot more granularity to it than that. For example, in the TKI [tyrosine kinase inhibitor] literature, there’s evidence that for intermediate-1 feature versus intermediate-2 feature, there’s a difference in outcome. And from favorable to intermediate risk there’s also perhaps a little bit of a fine line between those.

At this point in time, I look at whether the individual’s tumor biology is 1 that’s more than intermediate risk in terms of how it’s affecting them, how rapidly the disease is growing. It would be more a measure of disease erosivity that I would use as a measure of true “intermediate features” as opposed to good risk features. And that would help me make my decisions on how to treat.

Elizabeth R. Plimack, MD: IMDC [International Metastatic Renal-Cell Carcinoma Database Consortium] risk is pretty defined, and the factors that lead one to categorize as poor, intermediate, or favorable risk are really straightforward and easy to assess. With a clinical biomarker that effective, it doesn’t really behoove us to say, “It looks as if you’re poor risk, but really I think you’re favorable risk.” Or, “You’re intermediate risk, but you’re behaving like a good-risk patient.” Risk is risk, and I think you assign it and then you have to go from there.

That being said, I could imagine an intermediate-risk patient for whom we advise either observation or just a single-agent VEGF inhibitor because of other factors, because they don’t really want treatment. Length of life is not their goal. They want quality of life, they feel well, and they don’t want to interrupt that. That’s someone who might elect observation even if they’re in intermediate-risk category.

It’s really patient to patient, and 1 of the hardest things in meeting a new patient in a vulnerable situation where they’re just diagnosed with cancer is trying to get at what their values are and learn what’s important to them to really help guide them in decision making. It’s easy to say, “You’re intermediate risk, so you should go on axitinib-pembrolizumab, and we’re going to start next week.” Sometimes that’s the right thing. Often it’s the right thing. But until we get to know the patient and their values and where their priorities lie, we can’t really have a meaningful discussion about treatment.

Eric A. Jonasch, MD: In terms of practical considerations for treatment at this point, do I make a big distinction between favorable risk and intermediate risk? For a lot of the patients who I would be treating with favorable-risk features, I’d be giving an I/O [immuno-oncology]–TKI combination like axitinib plus pembrolizumab. I would be potentially doing that for a favorable intermediate-risk patient as well. It means that I don’t really treat those individuals very differently.

If the distinction would be between, for example, sunitinib and ipilimumab-nivolumab, there it becomes a little more important. Because if you look at the CheckMate 214 study in the favorable-risk-patient population, patients on sunitinib ended up having better progression-free survival and better objective response rate, albeit slightly lower complete response rate, compared with ipilimumab-nivolumab. As I said before, that distinction becomes less important when you’re thinking of an I/O-TKI combination versus a TKI.

Transcript Edited for Clarity