In RCC, What Is the Optimal Treatment for Intermediate/Poor-Risk Disease?

A roundtable discussion, moderated by Monty Pal, MD, of the City of Hope, focused on updates in renal cell carcinoma (RCC), including treatment in both the frontline and adjuvant settings. Dr. Pal was joined by a panel that included Daniel George, MD; Brad McGregor, MD; and Cristina Suárez Rodríguez, MD.

In the next segment of the roundtable series, the panel discusses considerations for treatment choice in patients with poor- and intermediate-risk disease.

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Dr. Pal: We talked about good-risk disease. Let’s talk about intermediate- and poor-risk disease. I’ll start with you, Cristina, this go around. This debate rages on perhaps even more intensely. Do you go with nivolumab/ipilimumab? Do you go with a tyrosine kinase inhibitor (TKI)/immuno-oncology (IO)-based regimen in that setting? We’ll dive into the nature of which TKI/IO in a bit, but in general, what do you find yourself looking toward for intermediate- and poor-risk disease?

Dr. Suarez: This is a really hard question. It’s difficult to answer. The only thing I have more or less is patients with rapidly progressive disease and usually use an IO/TKI because they have 5% of progressive disease in 2 trials, and the other is 10%. Some of those patients, you have just 1 shot, and you don’t want them to progress. In these patients, I would use IO/TKI. In patients with sarcomatoid features, I will use IO/IO because the results with nivolumab/ipilimumab are really very, very good. But the vast majority of patients that are not sarcomatoid and not rapidly progressive, it’s difficult to say something is better.

Dr. Pal: Yeah, absolutely. How do you weigh that decision making for intermediate- and poor-risk, Brad?

Dr. McGregor: I’m exactly the same way. I think that progressive disease (PD) has a best response of 20% with nivolumab/ipilimumab. Can I afford to be wrong? If you have a situation where they’re in that 20%, and you’re not going to get to that second-line therapy then you really have to think about it. I talk to my patient like, “Listen, we have 2 different things. Do we need to focus on now or do we have that luxury we can take a risk in the short-term?” Some patients, they looked at that idea of a treatment-free interval, that potential to be off therapy for a long period of time. I think nivolumab/ipilimumab does provide that in some patients.

If I have a situation where they’re not rapidly progressive disease and immediate/poor-risk situation, I definitely like nivolumab/ipilimumab. But I think similar to Cristina, if I have a patient where they have rapidly progressive disease, liver metastases, symptomatic lung metastases, symptomatic bones metastases, those are the patients that if you’re wrong and they’re that 20% PD as best response, they’re not going to be able to get to that second-line therapy. I’m really looking into that TKI/IO, as you said, that PD as best response is 5% or 6%, I think is certainly very appealing.

Dr. Pal: What I think I’m hearing from both views is that if you’ve got rapidly progressive disease, symptomatic, etc., in that intermediate/poor-risk category, you’re definitely leaning on TKI plus IO. I think in the patients who don’t fit into that bucket, there’s probably more of a conflict. Dan, where do you find yourself leading between those 2choices, specifically in that patient population?

Dr. George: The one thing I’ll say is I think it’s a little bit tricky sometimes with the pace of disease. I’m seeing this patient, they’re usually newly diagnosed presenting with metastatic disease, I don’t really know how fast is that disease going. Now, by symptoms sometimes I can tell: They’ve lost a bunch of weight in the last 3 months, or they’ve got a new pain they didn’t have 2 months, or what have you. But a lot of times, I’m a little bit lost at that, so I kind of go by symptom sites and burden of disease. Because if they’ve got a big burden of disease, chances are that that’s a disease that now I can’t allow that to get 30% bigger or 20% bigger, especially if it’s symptomatic and burdensome. That’s a disease that even a little bit of growth is going to be even more symptomatic and complications can happen—fractures, effusions, blood clots, all kinds of stuff. These are the patients I need a treatment effect. I need that tumor volume reduction, and I need it quickly.

What I love about these IO/TKIs is the ability to shrink cancer quickly. It gets back to what Brad said when I was saying earlier, like around the patients that can afford to go a few months. It’s hard to know with the pace of disease if I don’t have prior scans. But I can tell sometimes by those symptoms, and if the burden is not that high, then I can feel like even if these lung metastases increase, I’m going to be okay. They’re going to be okay. We can try this. If we can, I like the ipilimumab/nivolumab combination. It seems to be most effective in these intermediate/high-risk patients, even some of these high-burden patients. I don’t want to just automatically give up on that. It’s just that it has to be in a population I feel particularly comfortable with. That, to me, is the nuance. It’s hard to put it in a very specific quantitative setting. I have a sense of it based on experience in working with these patients.

Dr. Pal: I’m inferring from what you’re saying that probably the majority of folks in that bucket of patients, again, not rapidly progressing disease, but in patients where you can’t necessarily predict kinetics, you’re maybe leaning a little bit more still toward TKI/IO, and that tends to be my practice as well.

Dr. George: I think so. Sometimes people will say, well, the poor risk versus intermediate risk, I kind of see the poor and intermediate as 1 category. They all benefited from these therapies, and most of the clinical trial benefits that we saw in these trials were driven by this group of patients. I kind of lump them together. It gets back to these other factors that really differentiate between intermediate and poor populations who I choose 1 therapy in or another.

Dr. Pal: This debate just gets tougher and tougher and tougher here.

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Continue on to watch the next roundtable segment.