New First-Line Combination Therapies in Advanced RCC - Episode 5
Oncologists discuss how they select an appropriate novel combination strategy as first-line therapy for patients with favorable-risk metastatic renal cell carcinoma.
Sumanta Kumar Pal, MD: Brad, I’ll turn to you. In regard to the EAU [European Association of Urology] Guidelines and NCCN [National Comprehensive Cancer Network], David is saying, “Put them by the wayside.”
David F. McDermott, MD: You can say that. I said I put them by the wayside. You guys can follow the book if you want.
Sumanta Kumar Pal, MD: He’s right down the street from you, Brad. What’s going on at your shop over there? What are you guys doing for favorable-risk metastatic renal cell carcinoma?
Bradley A. McGregor, MD: I agree with Dave. It comes down to discussion with your patients. nivolumab-ipilimumab certainly has a role in favorable-risk patients. The benefit of nivolumab-ipilimumab tends to be its durability and long-term response. Of all the combinations, PD [progressive disease] as the best response is probably the highest. With a favorable-risk patient, you have the luxury to be wrong because you can always rescue with the next line of therapy. If you want to shoot for the stars and go for potential durable remission, nivolumab-ipilimumab offers the best chance. I will offer them nivolumab-ipilimumab. I have been a little leery of the TKI [tyrosine kinase inhibitors]–I/O [immuno-oncology] combinations in the favorable-risk population because of the synergistic toxicity. Although the PROs [patient-reported outcomes] with cabozantinib-nivolumab suggest that cabozantinib-nivolumab is well tolerated and maybe superior to sunitinib in some of those outcomes. It comes down to a discussion with your patients. We’re looking at novel approaches. We have a trial open in which we’re giving cabozantinib in combination with a HIF2 inhibitor in patients who are previously untreated. It’s a great option to give these patients a novel treatment if they’re looking to do something different. We try to explore novel approaches in that situation as well.
Sumanta Kumar Pal, MD: Your answer is somewhere between what Tom Hutson and David proposed for favorable-risk [patients]. Bob, what are you guys doing in New Jersey for favorable-risk disease?
Robert S. Alter, MD: We try to follow NCCN Guidelines, but I agree with Dave. Sometimes you have to not follow NCCN Guidelines. We’ve always had this conversation about cure. We go back to the high-dose IL-2 days. We haven’t talked about that. Nurses ask me why we haven’t used it in 3 or 4 years. It’s because we don’t think we need to. That was the same approach. We do have a small population of patients whom we should shoot for the stars for. I do believe immunotherapy has a role. There’s always that approach. You can always discontinue an immunotherapy drug, but it’s always difficult to discontinue a targeted VEGF inhibitor. When it comes down to it, if the patients are doing quite well, with a good PR [partial response], and you can actually give them a break, you feel very comfortable giving them immunotherapy with the possibility of rechallenging them. Sequencing is very good.
In the community, we have issues with cost. A lot of these patients have to pay out of pocket for oral therapies. Infused therapies in the cancer centers are covered. Sometimes, we think an oral TKI may be quite good for patients who are favorable risk, but we’re stuck with them being unable to afford it. Intravenous therapy may be the default because of finances rather than efficacy.
TRANSCRIPT EDITED FOR CLARITY