Abstract
BRAF inhibitors, specifically vemurafenib and dabrafenib, are emerging as first-line treatment for unresectable and/or metastatic BRAF mutated melanoma due to their superior efficacy and improved survival statistics. While better tolerated than previously used treatment options, they carry high rates of cutaneous reactions, with most BRAF-inhibitor treated patients experiencing at least one cutaneous adverse effect.
Photosensitivity, various skin rashes, skin papillomas, hyperkeratosis, verrucal keratoses, and cutaneous squamous cell carcinomas (SCCs) are some of the more common cutaneous toxicities reported to date. These are typically managed symptomatically without need for dose reduction or discontinuation of the BRAF inhibitor. MEK inhibitors are now being used in combination with BRAF inhibitors to improve efficacy, prevent drug resistance, and lower the rate of cutaneous reactions. This chapter focuses on the cutaneous reactions associated with the RAF inhibitor sorafenib and the BRAF inhibitors vemurafenib and dabrafenib.
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Anforth RM, Blumetti TC, Kefford RF, Sharma R, Scolyer RA, Kossard S, et al. Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma. Br J Dermatol. 2012;167:1153–60.
Anforth R, Fernandez-Penas P, Long GV. Cutaneous toxicities of RAF inhibitors. Lancet Oncol. 2013;14:e11–8.
Boussemart L, Routier E, Mateus C, Opletalova K, Sebille G, Kamsu-Kom N, et al. Prospective study of cutaneous side effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Ann Oncol. 2013;24:1691–7.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.
Chu EY, Wanat KA, Miller CJ, Amaravadi RK, Fecher LA, Brose MS, et al. Diverse cutaneous side effects associated with BRAF inhibitor therapy: a clinicopathologic study. J Am Acad Dermatol. 2012;67(6):1265–72.
Falchook GS, Long GV, Kutzrock R, Kim KB, Arkenau TH, Brown MP, et al. Dabrafenib in patients with melanoma, untreated brain metastasis, and other solid tumors: a phase I dose-escalation trial. Lancet. 2012;379(9829):1893–901.
Flaherty K, Infante JR, Falchook GS, et al. Phase I/II expansion cohort of BRAF inhibitor GSK2118436 + MEK inhibitor GSK1120212 in patients with BRAF mutant metastatic melanoma who progressed on a prior BRAF inhibitor. Pigment Cell Melanoma Res. 2012;25:E3.
Gelot P, Dutartre H, Khammari A, Boisrobert A, Schmitt C, Deybach JC, et al. Vemurafenib: an unusual UVA-induced photosensitivity. Exp Dermatol. 2013;22(4):297–8.
Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicenter, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358–65.
Huang V, Hepper D, Anadkat M, Cornelius L. Cutaneous toxic effects associated with vemurafenib and inhibition of the BRAF pathway. Arch Dermatol. 2012;148(5):628–33.
Larkin J, Del Vecchio M, Ascierto PA, Krajsova I, Schachter J, Neyns B, et al. Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an open-label, multicentre, safety study. Lancet Oncol. 2014;15(4):436–44.
Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, et al. Dabrafenib in patients with VAL600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicenter, open-label, phase 2 trial. Lancet Oncol. 2012;13:1087–95.
Mandala M, Massi D, DeGiorgi V. Cutaneous toxicities of BRAF inhibitors: clinical and pathological challenges and call to action. Clin Rev Oncol Hematol. 2013;88(2):318–37.
Martinez-Garcia M, Banerji U, Albanell J, Bahleda R, Dolly S, Kraeber-Bodéré F, et al. First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors. Clin Cancer Res. 2012;18:4806–19.
Mattei PL, MB A l-P, Kraft S, Lawrence DP, Flaherty KT, Kimball AB. Cutaneous effects of BRAF inhibitor therapy: a case series. Ann Oncol. 2013;24:530–7.
McArthur GA, Chapman PB, Robert C. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3 randomised, open-label study. Lancet Oncol. 2014;15:323–32.
Rinderknecht JD, Goldinger SM, Rozati S, Kamarashev J, Kerl K, French LE, et al. RASopathic skin eruptions during vemurafenib therapy. PLoS One. 2013;8(3):e58721.
Sinha R, Edmonds K, Newton-Bishop JA, Gore ME, Larkin J, Fearfield L. 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. Br J Dermatol. 2012;167:987–94.
Vanneste L, Wolter P, Van den Oord JJ, Stas M, Garmyn M. Cutaneous adverse effects of BRAF inhibitors in metastatic malignant melanoma, a prospective study in 20 patients. J Eur Acad Dermatol Venereol. 2015;29(1):61–8.
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McCoppin, H.H. (2015). Cutaneous Reactions to BRAF Inhibitors. In: Hall, J., Hall, B. (eds) Cutaneous Drug Eruptions. Springer, London. https://doi.org/10.1007/978-1-4471-6729-7_32
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DOI: https://doi.org/10.1007/978-1-4471-6729-7_32
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