Vemurafenib treatment for patients with locally advanced, unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E

Melanoma Res. 2017 Dec;27(6):585-590. doi: 10.1097/CMR.0000000000000398.

Abstract

BRAF mutations are found in ~50% of metastatic melanomas, most commonly in codon V600. Vemurafenib improves progression-free survival and overall survival in patients with advanced BRAF-mutated melanoma. The results of a descriptive study evaluating vemurafenib in patients with advanced melanoma harbouring BRAF mutations other than V600E are reported. Eligible patients with stage IIIC or IV melanoma and non-V600E BRAF mutations received vemurafenib (960 mg, twice daily). End points included investigator-assessed best overall response rate (primary), time to response, duration of response, progression-free survival, overall survival and safety. Planned (V600K vs. non-V600K mutations) subgroup analyses were carried out. Thirty-one patients were enrolled; 13 (42%) had V600K mutations and 18 (58%) had other mutations. Investigator-assessed confirmed that the best overall response rate was 23% (95% confidence interval=10-41%) in the overall population, and was similar between patients with V600K mutations (23%; 95% confidence interval=5-54%) versus other mutations (22%; 95% confidence interval=6-48%). Responses were observed in patients with V600K (n=3), V600E2 (n=1), V600R (n=1), L597S (n=1) and D594G (n=1) mutations. No new safety signals were reported. Vemurafenib showed activity in patients with advanced melanoma with rarer BRAF mutations.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Humans
  • Indoles / pharmacology
  • Indoles / therapeutic use*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Proto-Oncogene Proteins B-raf / genetics
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*
  • Vemurafenib

Substances

  • Antineoplastic Agents
  • Indoles
  • Sulfonamides
  • Vemurafenib
  • Proto-Oncogene Proteins B-raf