Cutaneous adverse effects of BRAF inhibitors in metastatic malignant melanoma, a prospective study in 20 patients. (24th March 2014)

• Record Type: Journal Article
• Authors: Vanneste, L.; Wolter, P.; Van den Oord, J.J.; Stas, M.; Garmyn, M.
• Is Part Of: Journal of the European Academy of Dermatology and Venereology. Volume 29:Number 1(2015:Jan.)
• Page Start: 61
• Page End: 68
• Publication Date: 2014-03-24
• Subjects: Dermatology -- Periodicals; Sexually transmitted diseases -- Periodicals; 616.5
• DOI: 10.1111/jdv.12449
• Languages: English
• ISSNs: 0926-9959

Abstract

<abstract abstract-type="main" id="jdv12449-abs-0001"> <title>Abstract</title> <sec id="jdv12449-sec-0001" sec-type="section"> <title>Background</title> <p>BRAF inhibitors frequently cause significant cutaneous adverse reactions.</p> </sec> <sec id="jdv12449-sec-0002" sec-type="section"> <title>Objective</title> <p>To study the timing, prevalence and response to treatment of skin lesions in patients receiving V‐raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors.</p> </sec> <sec id="jdv12449-sec-0003" sec-type="section"> <title>Methods</title> <p>We prospectively studied the cutaneous side‐effects of patients with a BRAF mutant (V600E, V600K, V600R) metastatic malignant melanoma treated with a BRAF inhibitor. We systematically registered prevalence, timing of onset and response to treatment.</p> </sec> <sec id="jdv12449-sec-0004" sec-type="section"> <title>Results</title> <p>Twenty patients were treated for 2–52 weeks with a BRAF inhibitor. Eleven patients on vemurafenib (58%) developed cutaneous side‐effects and 10 patients (42%) had more than one cutaneous adverse event. Verrucous papillomas were observed in eight patients (42%), after 1–12 weeks. We diagnosed four keratoacanthomas in two patients (11%) after 6–10 weeks and two squamous cell carcinomas in two patients (11%) after 10–16 weeks. Seven patients (37%) developed a hyperkeratotic, folliculocentric eruption after 2–8 weeks, resolving quickly under topical steroids. Four patients (21%) presented a facial erythema, two patients (11%) a seborrhoeic dermatitis‐like eczema on the scalp. Three patients (16%) developed cystic lesions after 2–11 weeks. Three patients (16%) presented a hand–foot skin reaction after 4–6 weeks, which was successfully treated with topical steroids and keratolytics. Hyperkeratosis of the nipples was seen in one patient (5%). We observed phototoxic reactions after UV exposure in five patients (26%) and alopecia in two patients (11%) after 8–10 weeks. One patient on dabrafenib developed curly hairs (24 weeks), keratotic papules (1 and 36 weeks), a keratoacanthoma (4 weeks) and a hand–foot skin reaction (31 weeks).</p> </sec> <sec id="jdv12449-sec-0005" sec-type="section"> <title>Conclusion</title> <p>Multiple cutaneous toxicities were observed in patients under BRAF inhibitors, mostly well controlled with adequate treatment. We recommend a multidisciplinary approach with regular assessments of the skin by a dermatologist. This allows early identification and adequate treatment to avoid premature discontinuation of a life‐prolonging therapy.</p> </sec> </abstract>