Analysis of Dermatologic Events in Vemurafenib-Treated Patients With Melanoma

作者：Lacouture Mario E^*; Duvic Madeleine; Hauschild Axel; Prieto Victor G; Robert Caroline; Schadendorf Dirk; Kim Caroline C; McCormack Christopher J; Myskowski Patricia L; Spleiss Olivia; Trunzer Kerstin; Su Fei; Nelson Betty; Nolop Keith B; Grippo Joseph F; Lee Richard J; Klimek Matthew J; Troy James L; Joe Andrew K

来源：Oncologist, 2013, 18(3): 314-322.

DOI：10.1634/theoncologist.2012-0333

• Vemurafenib
• Dermatologic
• cuSCC
• Keratoacanthoma

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). %26lt;br%26gt;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. %26lt;br%26gt;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%. %26lt;br%26gt;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 %26lt; 10% of patients. The Oncologist 2013;18:314-322

• 出版日期2013-3