Open-label, multicentre safety study of vemurafenib in 3219 patients with BRAFV600 mutation-positive metastatic melanoma

Christian U Blank, James Larkin, Ana M Arance, Axel Hauschild, Paola Queirolo, Michele Del Vecchio, Paolo A Ascierto, Ivana Krajsova, Jacob Schachter, Bart Neyns, Claus Garbe, Vanna Chiarion Sileni, Mario Mandalà, Helen Gogas, Enrique Espinosa, Geke A P Hospers, Wilson H Miller, Susan Robson, Martina Makrutzki, Vladan AnticMichael P Brown

Research output: Contribution to journalArticlepeer-review


BACKGROUND: The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAFV600 mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety.METHODS: This was an open-label, multicentre study of vemurafenib (960 mg bid) in patients with previously treated or untreated BRAF mutation-positive metastatic melanoma (cobas® 4800 BRAF V600 Mutation Test). The primary end-point was safety; efficacy end-points were secondary. An exploratory analysis was performed to assess safety outcomes in patients with long duration of response (DOR) (≥12 or ≥24 months).RESULTS: After a median follow-up of 32.2 months (95% CI, 31.1-33.2 months), 3079/3219 patients (96%) had discontinued treatment. Adverse events (AEs) were largely consistent with previous reports; the most common all-grade treatment-related AEs were arthralgia (37%), alopecia (25%) and hyperkeratosis (23%); the most common grade 3/4 treatment-related AEs were squamous cell carcinoma of the skin (8%) and keratoacanthoma (8%). In the exploratory analysis, patients with DOR ≥12 months (n = 287) or ≥24 months (n = 133) were more likely to experience grade 3/4 AEs than the overall population. No new specific safety signals were observed with longer vemurafenib exposure.CONCLUSIONS: After 2 years' follow-up, safety was maintained in this large group of patients with BRAFV600 mutation-positive metastatic melanoma who are more representative of routine clinical practice than typical clinical trial populations. These data suggest that long-term vemurafenib treatment is effective and tolerable without the development of new safety signals.
Original languageEnglish
Pages (from-to)176-184
Number of pages9
JournalEuropean Journal of Cancer
Publication statusPublished - Jul 2017


  • Adult
  • Aged
  • Antineoplastic Agents
  • Brain Neoplasms
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Indoles
  • Male
  • Melanoma
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins B-raf
  • Skin Neoplasms
  • Sulfonamides
  • Treatment Outcome
  • Clinical Trial
  • Journal Article
  • Multicenter Study
  • Research Support, Non-U.S. Gov't


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