FDA Approves Nivolumab/Ipilimumab Combination for Intermediate or Poor-Risk Advanced RCC

Approval is based on the results from CheckMate 214

On 16 April 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 randomised 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 (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 RCC with favourable-risk disease was not established.

The most common adverse reactions (reported in at least 20% of patients treated with the combination) were fatigue, rash, diarrhoea, 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.

Prescribing information for both nivolumab and ipilimumab have been updated with these results. Full prescribing information for nivolumab is available here and for ipilimumab here.

FDA granted these applications priority review and breakthrough therapy designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.