Analysis of dermatologic events in vemurafenib-treated patients with melanoma

Oncologist. 2013;18(3):314-22. doi: 10.1634/theoncologist.2012-0333. Epub 2013 Mar 1.


Background: Vemurafenib has been approved for the treatment of patients with advanced BRAF(V600E)-mutant melanoma. This report by the Vemurafenib Dermatology Working Group presents the characteristics of dermatologic adverse events (AEs) that occur in vemurafenib-treated patients, including cutaneous squamous cell carcinoma (cuSCC).

Methods: Dermatologic AEs were assessed from three ongoing trials of BRAF(V600E) mutation-positive advanced melanoma. Histologic central review and genetic characterization were completed for a subset of cuSCC lesions.

Results: A total of 520 patients received vemurafenib. The most commonly reported AEs were dermatologic AEs, occurring in 92%-95% of patients. Rash was the most common AE (64%-75% of patients), and the most common types were rash not otherwise specified, erythema, maculopapular rash, and folliculitis. Rash development did not appear to correlate with tumor response. Photosensitivity occurred in 35%-63% of patients, and palmar-plantar erythrodysesthesia (PPE) occurred in 8%-10% of patients. The severity of rash, photosensitivity, and PPE were mainly grade 1 or 2. In all, 19%-26% of patients developed cuSCC, mostly keratoacanthomas (KAs). The majority of patients with cuSCC continued therapy without dose reduction after resection. Genetic analysis of 29 cuSCC/KA samples demonstrated HRAS mutations in 41%.

Conclusions: Dermatologic AEs associated with vemurafenib treatment in patients with melanoma were generally manageable with supportive care measures. Dose interruptions and/or reductions were required in <10% of patients.

Trial registration: NCT00949702 NCT01006980 NCT01107418.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Clinical Trials as Topic
  • Female
  • Humans
  • Indoles / adverse effects*
  • Indoles / therapeutic use*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Neoplasms, Second Primary / chemically induced*
  • Neoplasms, Second Primary / therapy
  • Randomized Controlled Trials as Topic
  • Skin Diseases / chemically induced*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Sulfonamides / adverse effects*
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Vemurafenib
  • Young Adult


  • Indoles
  • Sulfonamides
  • Vemurafenib

Associated data