New First-Line Combination Therapies in Advanced RCC - Episode 4

Favorable-Risk mRCC: Combination Regimens Vs Single-Agent Therapy

April 7, 2021
Sumanta Kumar Pal, MD, City of Hope

,
Robert Alter, MD, John Theurer Cancer Center

,
David F. McDermott, MD, Dana Farber Harvard Cancer Center

,
Tian Zhang, MD, Duke Cancer Center

,
Bradley McGregor, MD, Dana-Farber Cancer Institute

,
Thomas E. Hutson, DO, PharmD, Texas Oncology

Factors that oncologists need to consider when deciding whether to initiate single-agent therapy or a novel combination regimen as frontline treatment for patients with favorable-risk metastatic renal cell carcinoma.

Sumanta Kumar Pal, MD: Let me ask you about that patient who’s favorable risk who may not meet your criteria for combination therapy for ipilimumab-nivolumab. What are you going to give those patients?

David F. McDermott, MD: Our criteria is that we offer it to everyone and let them choose not to do it. The only patients who truly can’t get it are patients with active autoimmune disease. Everyone else can get it. Some patients may not want it after you tell them about the risks and the fact that the chance of severe toxicity is twice as great when you add the ipilimumab. But we offer it to every single person. The only people we offer VEGF- and PD-1–based combos to have active symptoms and are spinning downhill pretty quickly. Those are not good-risk patients, as we all know. In good-risk patients, we try to take a pretty aggressive approach, but we don’t push it on patients. As Tian was saying, it’s a discussion. We talk about the pluses and minuses. We talk about the potential, while small, of long-term benefit off-treatment, which for many patients is their goal if they can reach it. Most patients can’t, but we have that discussion.

Sumanta Kumar Pal, MD: I’ll keep pushing you a little harder if you don’t mind. For that favorable-risk patient, you have that conversation. They say, “Listen, Dr McDermott. I’m just not up to nivolumab-ipilimumab.” In this case, what are you going to give that patient?

David F. McDermott, MD: We’d most likely give them single-agent nivolumab or, nowadays, single-agent pembrolizumab. We would not give an asymptomatic patient a TKI [tyrosine kinase inhibitor] because you’d be trading improvement in scans for reduction in quality of life. Save that drug for when the cancer speeds up. The outcomes are pretty similar. The fact that overall survival is comparable in both arms of these studies suggests that sequence works just as well in these good-risk patients. So we try to keep it simple and make sure that if we start with I/O [immuno-oncology] therapy, we don’t fool ourselves in thinking that progression is pseudoprogression. We almost never see that in kidney cancer, so at the first sign of progression in a good risk patient, we switch them to a TKI.

Sumanta Kumar Pal, MD: Tom, what do you think about that? I’m going to paraphrase what Dave said. He said to offer everyone ipilimumab-nivolumab. If they say, “Doctor, I don’t know about the adverse effects,” then give single-agent nivolumab. What are your thoughts? Do you dismiss the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] criteria in the same way?

Thomas E. Hutson, DO, PharmD: Even though many of us would want to dismiss the IMDC criteria, our electronic medical records—or at least those who oversee us—make us check the box 1 way or the other. That may have an impact on physician compensation. What I agree with Dave on is that the data suggest that you could use single-agent therapy and, if you’re focused on quality of life for the patient, then that should be the way to go. Your quality of life is going to be better in single agent, but I would make the argument that your quality of life would be better with single-agent TKI than it would be in combination also. We haven’t shown, for instance, that axitinib-pembrolizumab, cabozantinib-nivolumab, avelumab-axitinib, or lenvatinib-pembrolizumab are going to do that much better themselves in the favorable-risk population than just sequential VEGF TKI followed by an I/O therapy. That is what Dave was saying too, but he was taking the other side, focused on that better quality of life with an I/O. I would argue that the VEGF is also like that, depending on which VEGF inhibitor you choose. We know a lot about them now, and we can use them well. We don’t have to give Sutent 4/6 [4 weeks on, 6 weeks off]. We can do 2/1 [2 weeks, on, 1 week off]. People do better with that. We’re going to have to show that there is absolutely a reason for combination therapy, especially as we start talking about triplet therapy—heaven forbid—in the favorable-risk patient.

TRANSCRIPT EDITED FOR CLARITY

x