On April 16, 2018, the US Food and Drug Administration (FDA) granted approvals to nivolumab and ipilimumab (Opdivo and Yervoy, Bristol-Myers Squibb Co) in combination for the treatment of intermediate- or poor-risk, previously untreated advanced renal cell carcinoma (RCC).

The approvals were based on CheckMate 214 (NCT02231749), a randomized open-label trial. Patients with previously untreated advanced RCC received nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks for 4 doses followed by nivolumab monotherapy (3 mg/kg) every 2 weeks, or sunitinib 50 mg daily for 4 weeks followed by 2 weeks off every cycle.

Efficacy was evaluated in 847 patients with intermediate- or poor-risk disease. The trial demonstrated statistically significant improvements in overall survival (OS) and objective response rate (ORR) for 425 patients receiving the combination compared with 422 of those receiving sunitinib.

Estimated median OS was not estimable in the combination arm compared with 25.9 months in the sunitinib arm (HR, 0.63, 95% CI: 0.44, 0.89; p<0.0001). The ORR was 41.6% (95% CI: 36.9, 46.5) for the combination vs 26.5% (95% CI: 22.4, 31) in the sunitinib arm (p<0.0001).

The efficacy of the combination in patients with previously untreated RCC with favorable-risk disease was not established.

The most common adverse reactions (reported in at least 20% of patients treated with the combination) were fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite.

The recommended schedule and dose for this combination is nivolumab, 3 mg/kg, followed by ipilimumab, 1 mg/kg, on the same day every 3 weeks for 4 doses; then, nivolumab, 240 mg, every 2 weeks or 480 mg every 4 weeks.