The FDA has granted approvals to nivolumab and ipilimumab (Opdivo and Yervoy, Bristol-Myers Squibb) 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 three weeks for four doses followed by nivolumab monotherapy (3 mg/kg) every two weeks, or sunitinib (Sutent, Pfizer) 50 mg daily for four weeks followed by two weeks off every cycle.
Efficacy was evaluated in intermediate- or poor-risk patients (N = 847). The trial demonstrated statistically significant improvements in overall survival (OS) and objective response rate (ORR) for patients receiving the combination (n = 425) compared with those receiving sunitinib (n = 422). Estimated median OS was not estimable in the combination arm compared with 25.9 months in the sunitinib arm (hazard ratio, 0.63; 95% confidence interval [CI], 0.44–0.89; P < 0.0001). The ORR was 41.6% (95% CI, 36.9–46.5) for the combination versus 26.5% (95% CI, 22.4–31) in the sunitinib arm (P < 0.0001). The efficacy of the combination in patients with previously untreated renal cell carcinoma 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 three weeks for four doses, then nivolumab, 240 mg, every two weeks or 480 mg every four weeks.
Source: FDA; April 16, 2018.