AnalysisofDermatologic Events inVemurafenib-TreatedPatients WithMelanoma

Background. Vemurafenib has been approved for the treatment of patients with advanced BRAF-mutant melanoma. This report by the Vemurafenib DermatologyWorking 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 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 weremainly grade 1 or 2. In all, 19%–26% of patients developed cuSCC, mostly keratoacanthomas (KAs). The majority of patients with cuSCC continued therapywithout dose reduction after resection.Genetic analysis of 29 cuSCC/KA samples demonstrated HRASmutations in 41%. Conclusions. Dermatologic AEs associated with vemurafenib treatment in patients with melanoma were generally manageable with supportive care measures. Dose interruptions and/or reductionswere required in 10%ofpatients.TheOncologist2013;18:314–322 Implications for Practice: Vemurafenib has been approved for the treatment of patients with advanced BRAF-mutant melanoma. Skin toxicity is commonwith vemurafenib therapy, and themajority of patients are able to tolerate and continue therapy following symptomatic and/or localmanagement (e.g., surgical resection). Clinicians shouldbeawareof these toxicities tobetter educate andmanage their patients.

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