Nivolumab Approved for Third Indication: Advanced Renal Cell Carcinoma

Two months after being granted a Breakthrough Therapy designation by the FDA for metastatic renal cell carcinoma (mRCC), nivolumab was today approved by regulators for treating mRCC patients who have failed a certain type of prior therapy.

The approval was based on the results of a phase 3 trial published earlier this month in the New England Journal of Medicine, which compared nivolumab with everolimus in 821 patients with advanced clear-cell renal-cell carcinoma who had received prior treatment with 1 or 2 antiangiogenic agents. The randomized trial assigned patients to receive either an intravenous infusion of nivolumab (3mg/kg) every 2 weeks or oral everolimus (10 mg tablet, once daily). The secondary endpoints were objective response rate and safety, and the primary trial endpoint was overall survival. The study design allowed dose modification for everolimus but not for nivolumab.

This international study, dubbed Checkmate-025, recruited patients at 146 sites across 24 countries in 5 continents (North and South America, Australia, Asia, and Europe). Only 803 of the 821 patients were treated, with 406 in the nivolumab group and 397 in the everolimus group. By data cutoff in June 2015, 17% (67) of patients in the nivolumab group and 7% (28) in the everolimus group continued to receive treatment. Minimum follow-up period was 14 months and disease progression as the primary reason for discontinuation of treatment (observed in 70% of nivolumab-treated patients and 69% of everolimus-treated patients).

Patients in the nivolumab group had significantly better overall survival (25 months; 95% confidence interval (CI), 21.8 to not estimable) compared with those treated with everolimus (19.6 months; 95% CI, 17.6 to 23.1). Nearly 45% of patients (183 of 410) in the nivolumab cohort died, as opposed to 52% (215 of 411) in the everolimus group. The hazard ratio for all-cause death was 0.73 (98.5% CI, 0.57 to 0.93; P = .002) for nivolumab versus everolimus.

In the press release announcing the drug’s approval, Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said, “Opdivo [nivolumab] provides an important therapy option for patients with renal cell carcinoma. It is one of few therapies that have demonstrated the ability to extend patients’ survival in treating this disease. Additionally, Opdivo’s extended indication, from melanoma and non-small cell lung cancer to renal cell cancer, demonstrates how immune therapies can benefit patients across a wide range of tumors.”