Analysis of dermatologic events in vemurafenib-treated patients with melanoma

Abstract

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: ClinicalTrials.gov NCT00949702 NCT01006980 NCT01107418.

Figure 1.

Clinical and histologic presentation. (A): Maculopapular rash. (B): Maculopapular rash (histology). (C): Keratosis pilaris. (D): Keratosis pilaris rash (histology). (E): Photosensitivity. (F): Palmar-plantar erythrodysesthesia. (G): Cutaneous squamous cell carcinoma. (H): Cutaneous squamous cell carcinoma (histology). (I): Multiple cutaneous lesions: keratoacanthoma (black arrow), verruca (white circle), milia (white arrow). (J): Keratoacanthoma (histology).

Figure 2.

Management strategies for vemurafenib-associated macular rash, keratosis-pilaris rash, and hand–foot syndrome. Abbreviations: BID, twice daily; GABA, γ-aminobutyric acid; NSAID, nonsteroidal anti-inflammatory drug.