FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAF Wild-Type Unresectable or Metastatic Melanoma.

On November 23, 2015, the FDA approved nivolumab (OPDIVO; Bristol-Myers Squibb) as a single agent for the first-line treatment of patients with BRAF wild-type, unresectable or metastatic melanoma. An international, double-blind, randomized (1:1) trial conducted outside of the United States allocated 418 patients to receive nivolumab 3 mg/kg intravenously every 2 weeks ( = 210) or dacarbazine 1,000 mg/m intravenously every 3 weeks ( = 208). Patients with disease progression who met protocol-specified criteria (∼25% of each trial arm) were permitted to continue with the assigned treatment in a blinded fashion until further disease progression is documented. Overall survival was statistically significantly improved in the nivolumab arm compared with the dacarbazine arm [hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.30-0.60; < 0.0001]. Progression-free survival was also statistically significantly improved in the nivolumab arm (HR, 0.43; 95% CI, 0.34-0.56; < 0.0001). The most common adverse reactions (≥20%) of nivolumab were fatigue, diarrhea, constipation, nausea, musculoskeletal pain, rash, and pruritus. Nivolumab demonstrated a favorable benefit-risk profile compared with dacarbazine, supporting regular approval; however, it remains unclear whether treatment beyond disease progression contributes to the overall clinical benefit of nivolumab. .