Cutaneous adverse events to type I BRAF inhibitors: an analysis of effects associated with each inhibitor and therapeutic time interval to onset.
The treatment of malignant melanoma with inhibitors targeting the BRAF V600E mutation has demonstrated dramatic clinical and radiographic response with improved progression-free and overall survival in the majority of patients receiving treatment. However, cutaneous adverse effects-from proliferative processes to more classic drug side effects-are increasingly being reported in patients on BRAF inhibitors. In this comprehensive literature review we provide (1) an all-inclusive list of cutaneous adverse effects associated with selective class I RAF inhibitors, (2) specific adverse effects associated with each inhibitor, and (3) the therapeutic time interval associated with the onset of all reported lesion types. Twenty-two studies reporting cutaneous adverse reactions with selective class I RAF inhibitor therapy were retrieved from PubMed and sourced from relevant articles referenced by other papers. We identified over 45 differently described lesion types, corresponding to close to 2,000 cases. The most commonly reported lesion types in order of decreasing frequency include inflammatory dermatoses, benign lesions, malignant lesions, and hair/nail-related abnormalities. For the most part, the terminologies used in the original studies were retained. Case totals and time-to-lesion onset are presented for every group, and where available, for individual lesion types, by associated BRAF inhibitor.
Dermatopathology Section, Department of Dermatology, Boston University School Medicine, 609 Albany Street, Boston, MA, 02118, USA.
Dan C
DC
Filitis
Meera
M
Mahalingam
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D018572:Disease-Free Survival; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors
D000970:Antineoplastic Agents; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf