Dr. McDermott on Single-Agent Versus Combination Immunotherapy in RCC

David F. McDermott, MD, director of the Biologic Therapy Program at Beth Israel Deaconess Medical Center, discusses single-agent versus combination immunotherapy in the treatment of patients with renal cell carcinoma (RCC).

At the 2019 Genitourinary Cancers Symposium, there was a lot of interest in the studies looking at immunotherapy plus VEGF TKI combinations, but McDermott says the benefit of those combinations is mostly driven by PD-1 inhibition. Generally, single-agent checkpoint inhibition is a better-tolerated therapy for patients, so a question moving forward is whether researchers can identify a patient subset that will derive benefit from this approach versus others. However, the field is still a long way from that.

Combinations such as pembrolizumab (Keytruda) plus axitinib (Inlyta), which was evaluated in the KEYNOTE-426 trial, are also fairly well tolerated, but they add complexity, specifically in dealing with chronic adverse events associated with anti-VEGF therapy. CheckMate-214 introduced nivolumab (Opdivo) plus ipilimumab (Yervoy) as a very encouraging frontline option for patients with metastatic RCC, showing impressive response rates and opportunity for patients to go into remission. However, McDermott says it is crucial for providers to understand the unique toxicities of combining PD-1 and CTLA-4 inhibitors.