title: Cutaneous toxicities associated with vemurafenib therapy in 107 patients with BRAF V600E mutation-positive metastatic melanoma, including recognition and management of rare presentations.
abstract: BACKGROUND
  Vemurafenib significantly improved overall survival compared with dacarbazine in patients with metastatic or unresectable BRAF V600E-positive melanoma in the BRIM-3 trial. However, vemurafenib was associated with a number of skin-related adverse events (AEs).
  
  
  OBJECTIVE
  To investigate the incidence and management of vemurafenib-associated skin AEs.
  
  
  METHODS
  This retrospective, observational study included adult patients with stage IIIC or IV melanoma who received vemurafenib between March 2010 and August 2013. Patients received oral vemurafenib 960 mg twice daily, with dose interruptions and reductions allowed for AE management.
  
  
  RESULTS
  In total 107 patients were treated with vemurafenib during the study period. The most frequent clinically important skin-related AEs were rash (64%), squamoproliferative growths (41%), photosensitivity (40%) and squamous cell carcinoma (SCC) or keratoacanthoma (KA; 20%). Rare cases of granulomatous dermatitis and cutaneous T-cell lymphoma were also found. Rash was manageable with corticosteroids and dose modifications; squamoproliferative growths and SCCs/KAs were treated with cryotherapy and surgical excision, respectively. Patients were counselled regarding phototoxicity. The uncontrolled nature and retrospective design of the study, and the small patient numbers are limitations.
  
  
  CONCLUSIONS
  Vemurafenib appears to have a predictable and manageable AE profile. Proactive management can limit the impact of AEs on patients, allowing treatment to continue despite toxicities.
authors.affiliation: Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, U.K.|Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, U.K.
authors.forename: J
authors.initials: J
authors.lastname: Larkin
authors.affiliation: Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Gore
authors.affiliation: Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, U.K.|Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, U.K.
authors.forename: L
authors.initials: L
authors.lastname: Fearfield
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D005076:Exanthema / Q000235:genetics; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D007636:Keratoacanthoma / Q000139:chemically induced; D016410:Lymphoma, T-Cell, Cutaneous / Q000139:chemically induced; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010787:Photosensitivity Disorders / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D000077484:Vemurafenib; D055815:Young Adult
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf