Risk Stratification in Metastatic Renal Cell Carcinoma


Sumanta Kumar Pal, MD: Hello, and thank you for joining this OncLive Peer Exchange® discussion, “Practical Strategies for Treatment of Clear-Cell Renal Cell Carcinoma.” Research in the field of genitourinary oncology continues to provide us with paradigm-changing data in terms of how we treat our patients with systemic therapy. Recently I was joined by my colleagues Dr Neeraj Agarwal, Dr Bradley McGregor, and Dr Tian Zhang in a Twitter chat, during which we discussed some of the practical questions that plague the community oncologist when treating patients with metastatic renal cell carcinoma. It was really an engaging discussion in which we were also joined by several other experts in the field. In today’s OncLive Peer Exchange® discussion, we’re going to explore those questions further, as we share the insightful comments that we gathered from both kidney cancer experts and community-based oncologists on Twitter.

I’m Dr Sumanta Kumar Pal, an associate clinical professor in the Department of Medical Oncology & Therapeutics Research, and co-director of the Kidney Cancer Program at City of Hope in Duarte, California. I’m also a practicing medical oncologist. Joining me today is Dr Neeraj Agarwal, who’s a professor of medicine, a presidential endowed chair, and the director of the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah in Salt Lake City. I’m also joined by Dr Bradley McGregor, who’s an instructor of medicine and the clinical director for the Lank Center for Genitourinary Oncology and a GU [genitourinary] network liaison and the CSO cabinet director at Harvard Medical School at the Dana-Farber Cancer Institute in Boston, Massachusetts. Finally, I’m joined by Tian Zhang, an assistant professor of medicine in the Division of Medical Oncology in the Department of Medicine at the Duke Cancer Institute in Durham, North Carolina.

We have a lot of exciting things to cover today. Let’s get started on our first topic—the treatment of newly diagnosed disease—and some of the questions that we addressed on Twitter. Now, Tian, the first question that we actually touched on was risk stratification. We thought about it a lot and the past generation of treatments we had. How are you using risk stratification nowadays?

Tian Zhang, MD: I think it really panned out after we saw the CheckMate 214 data, which showed such a benefit with ipilimumab and nivolumab in the intermediate- or poor-risk patients but not so much in the favorable-risk patients. And so based on that, our NCCN [National Comprehensive Cancer Network] Guidelines really changed to reflect the importance of risk stratification. And so in our clinics we use IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk criteria to risk stratify our patients and get a sense of who has favorable-risk disease versus intermediate- or poor-risk disease with more guarded prognoses. And in turn, we figure out who should be treated with what types of treatments up front. And it’s so critical now, as we’re looking at more phase III data, to think about these clinical factors as we’re selecting treatments.

So we know the IMDC criteria are a list of clinical criteria that we teach our fellows all the time, and there are criteria of less than a year from nephrectomy to treatment, Karnofsky Performance Status, and then laboratory values that really reflect the inflammation of the disease process. So neutrophilia, anemia, and thrombocytosis are all through inflammatory markers. And then the hypercalcemia can sometimes be a marker of bone metastasis, which we know is a poor prognostic marker.

Sumanta Kumar Pal, MD: Interesting. That’s a great summary of the Heng criteria. Now, Brad, let me ask you, I’ve talked to a lot of community-based oncologists who say, “Look, those are impressive criteria, but I’m just going to look at the patient. And if they’re in a wheelchair, they’re poor risk. If they’re not, they’re good risk.” Tell us about that.

Bradley McGregor, MD: I think with the advent of the new data, it’s become more important to look at their risk criteria in more detail. Before it was something used to offer prognosis, and people might have said, “Well, I can offer just as good prognosis if I look at a patient.” But now data actually suggest which treatment you choose depends on the risk classification. And when you start thinking about that, I think it’s important that you can’t really eyeball risk stratification. Be willing to look at all the factors that come into play, and that should be 1 of the factors you use to determine what the best treatment is going to be for your patient.

Sumanta Kumar Pal, MD: I tend to agree with you. What’s interesting is that on Twitter we had a pretty healthy dialogue around good-risk disease, and Tian, you alluded to the NCCN criteria and how they play a role now in selecting therapy. Neeraj, 1 of the hotly debated items in our Twitter chat was what to do for good-risk disease. Is there a clear answer there? What’s your practice?

Neeraj Agarwal, MD: First of all, building upon what Tian said, a few years ago we were just using these criteria for prognostication, telling the patients how much time they had, statistically speaking. But then, the CheckMate 214 trial showed us that this was the first, in my view, validation of those criteria and how biologically relevant they were from our practice perspective. In the good-risk patient, the VEGF-TKI [tyrosine kinase inhibitor] approach was clearly superior to the combination checkpoint inhibitors as far as overall survival, progression-free survival, and response rates are concerned. Even though overall survival tends to be superior in both arms, response rates were so drastically improved with sunitinib compared with the ipilimumab/nivolumab combination. Even the progression-free survival. So I think in my view this is a different disease category, or different disease subtype, within the clear-cell type.

Tian Zhang, MD: Right. On the Twitter chat we talked a lot about how those favorable-risk patients may, because of this data, be more dependent on the angiogenesis mechanism and blood vessel formation and how that’s very critical. These patients really respond more to the VEGF-targeting TKIs more than they do to the immunotherapies. And so on the Twitter chat, we showed the breakout of the responses based on favorable risk versus an intermediate or poor risk, and I think you’re absolutely right, Neeraj. We see this really great improvement in response rates for sunitinib in the favorable-risk patients. And so in those favorable-risk patients, up until CheckMate 214, we were still using single-agent VEGF-TKI therapies.

Transcript Edited for Clarity

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