title: 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.
authors: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10022, USA. lacoutum@mskcc.org
authors: Mario E
authors: ME
authors: Lacouture
authors: Madeleine
authors: M
authors: Duvic
authors: Axel
authors: A
authors: Hauschild
authors: Victor G
authors: VG
authors: Prieto
authors: Caroline
authors: C
authors: Robert
authors: Dirk
authors: D
authors: Schadendorf
authors: Caroline C
authors: CC
authors: Kim
authors: Christopher J
authors: CJ
authors: McCormack
authors: Patricia L
authors: PL
authors: Myskowski
authors: Olivia
authors: O
authors: Spleiss
authors: Kerstin
authors: K
authors: Trunzer
authors: Fei
authors: F
authors: Su
authors: Betty
authors: B
authors: Nelson
authors: Keith B
authors: KB
authors: Nolop
authors: Joseph F
authors: JF
authors: Grippo
authors: Richard J
authors: RJ
authors: Lee
authors: Matthew J
authors: MJ
authors: Klimek
authors: James L
authors: JL
authors: Troy
authors: Andrew K
authors: AK
authors: Joe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D012871:Skin Diseases / Q000139:chemically induced*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077484:Vemurafenib; D055815:Young Adult
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib