Scientific Publications by FDA Staff

Clin Cancer Res 2017 Jul 15;23(14):3479-83

FDA approval of nivolumab for the first-line treatment of patients with BRAFV600 wild-type unresectable or metastatic melanoma.

Beaver JA, Theoret MR, Mushti S, He K, Libeg M, Goldberg K, Sridhara R, McKee AE, Keegan P, Pazdur R

On November 23, 2015, the U.S. Food and Drug Administration approved nivolumab (OPDIVO(R), Bristol Myers Squibb, Co.) as a single agent for the first-line treatment of patients with BRAFV600 wild-type, unresectable or metastatic melanoma. An international, double-blind, randomized (1:1) trial conducted outside of the U.S. allocated 418 patients to receive nivolumab 3mg/kg intravenously every 2 weeks (n=210) or dacarbazine 1000mg/m2 intravenously every 3 weeks (n=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 (OS) was statistically significantly improved in the nivolumab arm compared to the dacarbazine arm [HR 0.42; 95% confidence interval (CI): 0.30-0.60; p < 0.0001]. Progression-free survival was also statistically significantly improved in the nivolumab arm (HR 0.43: 95% CI, 0.34-0.56; P < 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 to dacarbazine supporting regular approval; however, it remains unclear whether treatment beyond disease progression contributes to the overall clinical benefit of nivolumab.