Cutaneous side effects (cAE) of vemurafenib (V): Single-center cohort study of 28 metastatic melanoma (mM) patients (pts).

Author:

Goldinger Simone M.1,Rinderknecht Jeannine Desiree1,Belloni Benedetta1,Eggmann Nina1,Dummer Reinhard2

Affiliation:

1. University Hospital of Zurich, Zurich, Switzerland

2. Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland

Abstract

e19017 Background: V is a potent BRAF inhibitor with significant impact on progression-free and overall survival in mM pts. cAE are very common. This single-center observation analyses the clinical and histological spectrum of this new class-specific cAE in 28 pts treated with V in different clinical trials. Methods: 28 mM pts stage IV were treated with V 960mg b.i.d. in local ethic committees approved clinical trials. Occurring side effects were collected and documented prospectively. 65 biopsies were analysed. cAE were classified by reaction pattern as inflammatory diseases, hair and nail changes, keratinocytic proliferations, melanocytic disorders and proliferations. Results: V was well tolerated; in 2 pts dose reduction was necessary due to arthragia. 26/28 pts (93%) experienced cAE. UVA dependent photosensitivity and maculopapular exanthema were observed in 16 and 14 pts respectively. The histology of the rash demonstrated alteration of eccrine and follicular structures with mild inflammation and no increased keratinocytic apoptosis, thus differing from the rash of MEK inhibitors. Pruritus was observed in 8, folliculitis in 5, and burning feet in 3 pts. Hair thinning and alopecia occurred in 8 pts, 2 pts presented with curly hair. Follicular hyperkeratosis and acanthopapilloma were common skin reactions (n=12/n=13), as well as plantar hyperkeratosis (n=4), keratoacanthoma (n=5) and invasive squamous cell carcinoma (n=4). Histology of the acanthopapilloma (n=39) showed marked hyperkeratosis and acanthosis with koilocytes and mitosis, suggesting viral association. Single observations of morbus Bowen, Bowen carcinoma, basal cell carcinoma and a warty dyskeratoma were documented. 1 pt developed after more than 4 months of therapy a secondary primary melanoma on the capillitium (BRAF and RAS wildtype). Conclusions: V has a broad and particular cAE profile involving epidermis and adnexals. Regular skin examination by experienced dermatologists is crucial under V to detect and treat the possible side effects promptly. The treatment is very well tolerated but can have an impact in quality of life; ergo the pts have to be well informed. UVA optimized photoprotection is essential.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Panniculitis in Patients Treated With BRAF Inhibitors;The American Journal of Dermatopathology;2014-06

2. Pruritus to anticancer agents targeting the EGFR, BRAF, and CTLA-4;Dermatologic Therapy;2013-03

3. Cutaneous toxicities of RAF inhibitors;The Lancet Oncology;2013-01

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