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).

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.

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%.

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.