FDA has 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.
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 intermediate or poor-risk patients (n=847). The trial demonstrated statistically significant improvements in overall survival and objective response rate 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% 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 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.
Prescribing information for both nivolumab and ipilimumab have been updated with these results. Full prescribing information is available online: Nivolumab PI and Ipilimumab PI.
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