FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation

Clin Cancer Res. 2014 Oct 1;20(19):4994-5000. doi: 10.1158/1078-0432.CCR-14-0776. Epub 2014 Aug 5.

Abstract

On August 17, 2011, the U.S. Food and Drug Administration (FDA) approved vemurafenib tablets (Zelboraf, Hoffmann-LaRoche Inc.) for the treatment of patients with unresectable or metastatic melanoma with the BRAF(V600E) mutation as detected by an FDA-approved test. The cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems, Inc.) was approved concurrently. An international, multicenter, randomized, open-label trial in 675 previously untreated patients with BRAF(V600E) mutation-positive unresectable or metastatic melanoma allocated 337 patients to receive vemurafenib, 960 mg orally twice daily, and 338 patients to receive dacarbazine, 1,000 mg/m(2) intravenously every 3 weeks. Overall survival was significantly improved in patients receiving vemurafenib [HR, 0.44; 95% confidence interval (CI), 0.33-0.59; P < 0.0001]. Progression-free survival was also significantly improved in patients receiving vemurafenib (HR, 0.26; 95% CI, 0.20-0.33; P < 0.0001). Overall response rates were 48.4% and 5.5% in the vemurafenib and dacarbazine arms, respectively. The most common adverse reactions (≥30%) in patients treated with vemurafenib were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, and nausea. Cutaneous squamous cell carcinomas or keratoacanthomas were detected in approximately 24% of patients treated with vemurafenib. Other adverse reactions included hypersensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, uveitis, QT prolongation, and liver enzyme laboratory abnormalities.

Publication types

  • Letter
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • Drug Approval*
  • Drug Evaluation, Preclinical
  • Humans
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Indoles* / therapeutic use
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Melanoma / mortality
  • Melanoma / pathology
  • Mutation
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins B-raf / genetics
  • Sulfonamides* / chemistry
  • Sulfonamides* / pharmacology
  • Sulfonamides* / therapeutic use
  • Treatment Outcome
  • United States
  • United States Food and Drug Administration*
  • Vemurafenib

Substances

  • Antineoplastic Agents
  • Indoles
  • Sulfonamides
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf