Cutaneous adverse effects of BRAF inhibitors in metastatic malignant melanoma, a prospective study in 20 patients.

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Abstract

Background

BRAF inhibitors frequently cause significant cutaneous adverse reactions.

Objective

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.

Methods

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.

Results

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).

Conclusion

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.

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