Cutaneous adverse events associated with vemurafenib in patients with metastatic melanoma: practical advice on diagnosis, prevention and management of the main treatment-related skin toxicities

Abstract

Until recently, no effective treatment was available for patients with metastatic malignant melanoma, and median overall survival was little more than 6 months with the current standard of care, dacarbazine. In 2012, the first specific BRAF mutation inhibitor, vemurafenib, was licensed for the monotherapy of adults with BRAF V600 mutation-positive unresectable or metastatic melanoma. Like other targeted therapies, vemurafenib is associated with a predictable pattern of adverse events, including skin toxicities. We review the most common cutaneous adverse events associated with vemurafenib, based on data from clinical trials, and our own experiences of treating patients in trials and clinical practice. Overall, these toxicities are not preventable, but they rarely necessitate permanent treatment discontinuation and are generally manageable with dose modification and supportive care. We provide a treatment algorithm offering guidance on the most appropriate approach to managing the main skin toxicities to help clinicians unfamiliar with this novel agent to become confident in using vemurafenib effectively in the management of patients with metastatic melanoma.

Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma

“…Rash, photosensitivity, pruritis, dry skin, papilloma, alopecia, keratoacanthoma and SCC are the signature of BRAFi monotherapy, with photosensitivity being primarily associated with vemurafenib. Excellent practical advice on diagnosis, prevention and management of the main BRAFi-induced skin effects has previously been published by Sinha et al (2012) and are summarized in Fig. 1(a, b).…”

The use of vemurafenib in Australian patients with unresectable or metastatic melanoma containing the V600 BRAF gene mutation

“…18,32 These include prominent follicular plugging, palmar-plantar hyperkeratosis, exuberant seborrheic dermatitis-like hyperkeratosis of the face, keratosis pilaris and diffuse spiny follicular hyperkeratosis. Other cutaneous AEs are also very common and range from severe photosensitivity to UVA, [46][47][48][49][50] alopecia, 49 nail changes, 50 pruritis, 51 folliculitis, 52 acneiform dermatitis, 53 macular, papular or erythematous eruptions, 51,54 and xerosis. 52,55 Alopecia often comprises hair thinning that may not be noticeable in many individuals.…”

“…Other cutaneous AEs are also very common and range from severe photosensitivity to UVA, [46][47][48][49][50] alopecia, 49 nail changes, 50 pruritis, 51 folliculitis, 52 acneiform dermatitis, 53 macular, papular or erythematous eruptions, 51,54 and xerosis. 52,55 Alopecia often comprises hair thinning that may not be noticeable in many individuals. Less common skin reactions include exfoliative exanthema, 52 panniculitis, 56-61 erythema nodosum (appearing 15 days after initiation of therapy), 57 severe hydradenitis of the scalp and eruptive melanocytic nevi.…”

“…52,55 Alopecia often comprises hair thinning that may not be noticeable in many individuals. Less common skin reactions include exfoliative exanthema, 52 panniculitis, 56-61 erythema nodosum (appearing 15 days after initiation of therapy), 57 severe hydradenitis of the scalp and eruptive melanocytic nevi. 32,62 From an Australian perspective, the impact of vemurafenib AEs such as photosensitivity will be greater in those places with high UVA radiation, increasing the risk of significant photosensitivity even over short periods of time.…”

The management of Skin Toxicity Associated with Vemurafenib in Metastatic Malignant Melanoma

“…Vemurafenib ve dabrafenib V600E ve V600K mutasyonu taşıyan metastatik MM'de genel sağkalım katkısı gösterilmiş ajanlardır (1,2). Bununla birlikte diğer hedefe yönelik tedavilerde olduğu gibi vemurafenib kullanımında da çok sayıda cilt toksisitesi görülebilmektedir (3,4). Kutanöz yan etkiler vemurafenib tedavisinde nadiren kalıcı tedavi kesilmesini gerektiren, doz modifikasyonu ve destekleyici tedavi ile genellikle yönetilebilir bir durumdur.…”