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Diverse cutaneous side effects associated with BRAF inhibitor therapy: a clinicopathologic study. J Am Acad Dermatol 2012 Dec;67(6):1265-72 PMID: 22609219 PMCID: PMC4838029

Pubmed ID

22609219

DOI

10.1016/j.jaad.2012.04.008

Abstract

BACKGROUND: Vemurafenib, a novel selective small molecule inhibitor of BRAF, has recently been shown to be effective in the treatment of melanomas harboring the BRAF V600E mutation. Similar to the broad-spectrum RAF inhibitor sorafenib, vemurafenib induces development of squamous cell carcinomas and keratoacanthomas as a side effect of therapy.

OBJECTIVE: We sought to detail additional cutaneous adverse effects of vemurafenib and a similar BRAF inhibitor, dabrafenib.

METHODS: We evaluated the clinical and histologic feature of skin side effects developing on vemurafenib or dabrafenib therapy in 14 patients.

RESULTS: Eight patients developed one or more squamous cell carcinomas, and 11 patients formed benign verrucous keratoses. Eight patients developed single lesions and/or widespread eruptions with histopathologic findings of acantholytic dyskeratosis, consistent with warty dyskeratomas and Darier- or Grover-like rashes, respectively. One patient developed palmoplantar hyperkeratosis, and darkening of existing nevi and new nevi within 2 months of starting vemurafenib. Side effects presented as early as 1 week after beginning therapy, with a mean time of onset of 12.6 weeks in our cohort.

LIMITATIONS: This study was limited by the small number of cases, all from a single institution.

CONCLUSION: Selective BRAF inhibitor therapy is associated with the development of malignant and benign growths, including keratoacanthoma-like squamous cell carcinomas, warty dyskeratomas, and verrucous keratoses, along with widespread eruptions with histologic features of acantholytic dyskeratosis. Given the potential for malignant lesions to develop on treatment, awareness of potential adverse effects of these agents is necessary, and a low threshold for biopsy of new growths is recommended.

Author List

Chu EY, Wanat KA, Miller CJ, Amaravadi RK, Fecher LA, Brose MS, McGettigan S, Giles LR, Schuchter LM, Seykora JT, Rosenbach M

Author

Karolyn A. Wanat MD Associate Professor in the Dermatology department at Medical College of Wisconsin




Scopus

2-s2.0-84869104359   115 Citations

MESH terms used to index this publication - Major topics in bold

Aged, 80 and over
Carcinoma, Squamous Cell
Female
Humans
Indoles
Keratoacanthoma
Male
Melanoma
Middle Aged
Proto-Oncogene Proteins B-raf
Skin Neoplasms
Sulfonamides
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad