Survival in BRAF V600-mutant Advanced Melanoma Treated With Vemurafenib

N Engl J Med. 2012 Feb 23;366(8):707-14. doi: 10.1056/NEJMoa1112302.

Abstract

Background: Approximately 50% of melanomas harbor activating (V600) mutations in the serine-threonine protein kinase B-RAF (BRAF). The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600-mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial.

Methods: We designed a multicenter phase 2 trial of vemurafenib in patients with previously treated BRAF V600-mutant metastatic melanoma to investigate the efficacy of vemurafenib with respect to overall response rate (percentage of treated patients with a tumor response), duration of response, and overall survival. The primary end point was the overall response rate as ascertained by the independent review committee; overall survival was a secondary end point.

Results: A total of 132 patients had a median follow-up of 12.9 months (range, 0.6 to 20.1). The confirmed overall response rate was 53% (95% confidence interval [CI], 44 to 62; 6% with a complete response and 47% with a partial response), the median duration of response was 6.7 months (95% CI, 5.6 to 8.6), and the median progression-free survival was 6.8 months (95% CI, 5.6 to 8.1). Primary progression was observed in only 14% of patients. Some patients had a response after receiving vemurafenib for more than 6 months. The median overall survival was 15.9 months (95% CI, 11.6 to 18.3). The most common adverse events were grade 1 or 2 arthralgia, rash, photosensitivity, fatigue, and alopecia. Cutaneous squamous-cell carcinomas (the majority, keratoacanthoma type) were diagnosed in 26% of patients.

Conclusions: Vemurafenib induces clinical responses in more than half of patients with previously treated BRAF V600-mutant metastatic melanoma. In this study with a long follow-up, the median overall survival was approximately 16 months. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00949702.).

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Disease Progression
  • Female
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / secondary
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis / drug therapy
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Vemurafenib

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00949702