Cutaneous adverse events associated with vemurafenib in patients with metastatic melanoma: practical advice on diagnosis, prevention and management of the main treatment-related skin toxicities.
Until recently, no effective treatment was available for patients with metastatic malignant melanoma, and median overall survival was little more than 6 months with the current standard of care, dacarbazine. In 2012, the first specific BRAF mutation inhibitor, vemurafenib, was licensed for the monotherapy of adults with BRAF V600 mutation-positive unresectable or metastatic melanoma. Like other targeted therapies, vemurafenib is associated with a predictable pattern of adverse events, including skin toxicities. We review the most common cutaneous adverse events associated with vemurafenib, based on data from clinical trials, and our own experiences of treating patients in trials and clinical practice. Overall, these toxicities are not preventable, but they rarely necessitate permanent treatment discontinuation and are generally manageable with dose modification and supportive care. We provide a treatment algorithm offering guidance on the most appropriate approach to managing the main skin toxicities to help clinicians unfamiliar with this novel agent to become confident in using vemurafenib effectively in the management of patients with metastatic melanoma.
Department of Dermatology, Chelsea and Westminster Hospital, London SW10 9NH, U.K.
R
R
Sinha
K
K
Edmonds
J A
JA
Newton-Bishop
M E
ME
Gore
J
J
Larkin
L
L
Fearfield
D002986:Clinical Trials as Topic; D003875:Drug Eruptions / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D008545:Melanoma / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000188:drug therapy*; D013449:Sulfonamides / Q000009:adverse effects*; D000077484:Vemurafenib
D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf