Dr Voss on the Evaluation of Nivolumab/Ipilimumab in Intermediate/Poor-Risk RCC

Martin H. Voss, MD, genitourinary medical oncologist, clinical director, Genitourinary Medical Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the evaluation of nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)-classified intermediate/poor-risk renal cell carcinoma (RCC) in the phase 3 CheckMate 214 trial (NCT02231749).

The combination of ipilimumab and nivolumab has long been endorsed by the National Comprehensive Cancer Network (NCCN) as a preferred regimen for patients with intermediate- and poor-risk RCC based on the findings from the CheckMate 214 trial, Voss begins. This trial was primarily designed to assess the efficacy of ipilimumab plusnivolumab vs sunitinib (Sutent) in patients with IMDC intermediate- or poor-risk disease. CheckMate 214 met all its coprimary end points, demonstrating benefits in overall response rate (ORR) and progression-free survival (PFS), he emphasizes. Although the trial allowed the enrollment of favorable-risk patients, they were not included in the primary efficacy analysis, Voss reports. A secondary analysis of this subgroup showed that in the short term, patients with favorable-risk disease had better outcomes with sunitinib monotherapy, as reflected by higher ORRs, better PFS signals, and comparable overall survival (OS) outcomes, he adds.

Due to these findings, the NCCN endorsement and the FDA label for this combination in RCC initially focused solely on patients with intermediate- and poor-risk disease, he continues. However, since the original analysis, the data from CheckMate 214, including results from the favorable-risk subset, have undergone multiple re-analyses with extended follow-up periods, Voss explains. The most recent analysis, findings from which were presented at various meetings, now includes a median follow-up of approximately 8 years, he states. This extended dataset has provided insights into several long-term outcomes, including duration of response, long-term PFS, and OS. Notably, a new investigational end point, treatment-free survival, has emerged as a key measure of benefit in the context of immunotherapy for kidney cancer, highlighting the potential of nivolumab plus ipilimumab to generate durable responses without ongoing treatment, Voss concludes.