title: FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600Wild-Type Unresectable or Metastatic Melanoma.
abstract: On November 23, 2015, the FDA approved nivolumab (OPDIVO; Bristol-Myers Squibb) as a single agent for the first-line treatment of patients with BRAFV600wild-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 (n= 210) or dacarbazine 1,000 mg/m2intravenously 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 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;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 with dacarbazine, supporting regular approval; however, it remains unclear whether treatment beyond disease progression contributes to the overall clinical benefit of nivolumab.Clin Cancer Res; 23(14); 3479-83. ©2017 AACR.
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland. Julia.Beaver@fda.hhs.gov.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Beaver
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Theoret
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Sirisha
authors.initials: S
authors.lastname: Mushti
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Meredith
authors.initials: M
authors.lastname: Libeg
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Goldberg
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Amy E
authors.initials: AE
authors.lastname: McKee
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D000077594:Nivolumab; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000911:Antibodies, Monoclonal; D000077594:Nivolumab; D003606:Dacarbazine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf