Nivolumab/Ipilimumab Combo Approved for Advanced RCC

The US Food and Drug Administration (FDA) has approved the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for treatment of intermediate- or poor-risk, previously untreated advanced renal cell carcinoma (RCC).

The approvals are based on the results of Checkmate-14, a randomized open-label phase III trial that used dosing optimized for the setting of advanced RCC. A total of 847 patients with previously untreated advanced RCC received nivolumab at 3 mg plus ipilimumab at 1 mg every 3 weeks for 4 doses, followed by nivolumab monotherapy at 3 mg every 2 weeks, or sunitinib, the current standard of care, at 50 mg daily for 4 weeks followed by 2 weeks off every cycle.

“Our goal is to provide cancer patients with medicines that have the potential to extend their lives. As the first treatment option to increase overall survival for subgroups of patients with advanced RCC compared to sunitinib, the [nivolumab] plus low-dose [ipilimumab] combination helps deliver on that promise,” Johanna Mercier, head, US Commercial, Bristol-Myers Squibb, said in a press release.

The trial showed significant improvements in the overall survival (OS) and objective response rate (ORR) for the 425 patients who received the nivolumab/ipilimumab combination, compared with the 422 patients who received sunitinib.

Median OS was not yet reached estimable in the combination arm (95% CI, 28.2 to not estimable), and was 25.9 months in the sunitinib arm (hazard ratio [HR], 0.63; 95% CI, 0.44–0.89; P < .0001). ORR was 41.6% (95% CI, 36.9­–46.5) for the combination, and 26.5% (95% CI, 22.4–31) in the sunitinib arm (P < .0001). A greater number of complete responses were also seen in patients who received the combination (9.4% vs 1.2% with sunitinib). Results of treatment with the combination in patients with previously untreated favorable-risk RCC were not established.

Common adverse reactions included fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite.

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