Study findings demonstrate the long-term benefits of combining nivolumab therapy plus ipilimumab in treatment-naïve patients with advanced renal cell carcinoma (RCC) across all risk categories (Lancet Oncol. 2019 Aug 16. Epub ahead of print).

“In the ongoing phase 3 CheckMate 214 trial, nivolumab plus ipilimumab showed superior efficacy over sunitinib in patients with previously untreated intermediate-risk or poor-risk advanced renal cell carcinoma, with a manageable safety profile,” explained Robert J. Motzer, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, and colleagues, who sought to evaluate the long-term clinical benefit of nivolumab plus ipilimumab versus sunitinib in this population.

A total of 1096 patients with previously untreated, advanced, or metastatic RCC were enrolled in the phase 3, controlled study and randomized to receive nivolumab plus ipilimumab or sunitinib (550 vs 546 in the intention-to-treat population; 425 vs 422 intermediate-risk or poor-risk patients; and 125 vs 124 favorable-risk patients, respectively).

The primary end points were overall survival (OS), progression-free survival (PFS) per independent radiology review committee (IRRC), and objective responses per IRRC in intermediate- or poor-risk patients, and secondary end points were OS, PFS per IRRC, and objective responses per IRRC in the intention-to-treat population, and adverse events in all treated patients.

Among intermediate- or poor-risk patients, and with extended follow-up (median, 32.4 months), nivolumab plus ipilimumab maintained superiority over sunitinib with regard to OS (median, not reached vs 26.6 months, respectively; hazard ratio [HR], 0.66; 95% CI, 0.54-0.80; P <.0001), PFS (median, 8.2 months vs 8.3 months, respectively; HR, 0.77; 95% CI, 0.65-0.90; P = .0014), and the proportion of patients achieving an objective response (178 [42%] of 425 vs 124 [29%] of 422, respectively; P = .0001).

Nivolumab plus ipilimumab also showed improved efficacy compared with sunitinib in intention-to-treat patients in terms of OS (median, not reached vs 37.9 months, respectively; HR, 0.71; 95% CI, 0.59-0.86; P = .0003), PFS (median, 9.7 months vs 9.7 months, respectively; HR, 0.85; 95% CI, 0.73-0.98; P = .027), and the proportion of patients achieving an objective response (227 [41%] of 550 vs 186 [34%] of 546, respectively; P = .015).

The most common grade 3-4 treatment-related adverse events with nivolumab and ipilimumab were increased lipase, increased amylase, and increased alanine aminotransferase, whereas in the sunitinib arm they were hypertension, fatigue, and palmar-plantar erythrodysesthesia. There were 8 and 4 treatment-related deaths reported in each therapy arm, respectively.

“The results suggest that the superior efficacy of nivolumab plus ipilimumab over sunitinib was maintained in intermediate-risk or poor-risk and intention-to-treat patients with extended follow-up, and show the long-term benefits of nivolumab plus ipilimumab in patients with previously untreated advanced renal cell carcinoma across all risk categories,” Dr Motzer and colleagues concluded.—Hina Porcelli