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)
Cited by
3 articles.
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