Original articleDiverse cutaneous side effects associated with BRAF inhibitor therapy: A clinicopathologic study
Section snippets
Case 1
A 47-year-old Caucasian woman (patient 1, Table I) was diagnosed with stage IV melanoma with lung involvement, and was found to have V600E mutation in BRAF. Vemurafenib 960 mg twice daily was initiated, and 12 weeks after beginning therapy she noticed new scaly papules on the central aspect of her chest (Fig 1, A), upper aspect of her shoulders, back, and face. Several biopsies were performed at these sites. A biopsy from a 2-mm, pink, hyperkeratotic papule on the central aspect of her chest
Discussion
Vemurafenib and dabrafenib commonly induce cutaneous reactions. Each of the 14 patients (13 with metastatic melanoma and one with metastatic thyroid cancer) reported here developed one or more skin side effects after initiation of vemurafenib or dabrafenib treatment, and 13 of the 14 exhibited at least two different types of skin reactions (Table I). Verrucous keratoses were most commonly observed, occurring in 12 of 14 patients. SCCs and acantholytic eruptions each appeared in 8 of the 14
References (42)
- et al.
Squamous cell carcinoma in a patient receiving sorafenib
Ann Dermatol Venereol
(2011) - et al.
Cutaneous squamous cell carcinoma and inflammation of actinic keratoses associated with sorafenib
Clin Genitourin Cancer
(2009) - et al.
Sorafenib-induced multiple eruptive keratoacanthomas
Ann Dermatol Venereol
(2009) - et al.
Keratoacanthomas associated with sorafenib therapy
J Am Acad Dermatol
(2007) - et al.
The histologic spectrum of epithelial neoplasms induced by sorafenib
J Am Acad Dermatol
(2009) - et al.
Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF
Cell
(2010) - et al.
The Raf-MEK-ERK cascade represents a common pathway for alteration of intracellular calcium by Ras and protein kinase C in cardiac myocytes
J Biol Chem
(1998) - et al.
Dermatologic symptoms associated with the multikinase inhibitor sorafenib
J Am Acad Dermatol
(2009) - et al.
Vemurafenib
Nat Rev Drug Discov
(2011) - et al.
Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
Nature
(2010)
Improved survival with vemurafenib in melanoma with BRAF V600E mutation
N Engl J Med
Inhibition of mutated, activated BRAF in metastatic melanoma
N Engl J Med
Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib
N Engl J Med
BRAF targeted therapy changes the treatment paradigm in melanoma
Nat Rev Clin Oncol
Ultraviolet A and photosensitivity during vemurafenib therapy
N Engl J Med
Induction of cutaneous squamous cell carcinomas by RAF inhibitors: cause for concern?
J Clin Oncol
MC1R germline variants confer risk for BRAF-mutant melanoma
Science
Subungual keratoacanthoma
Am J Dermatopathol
RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors
J Clin Oncol
RAF inhibition and induction of cutaneous squamous cell carcinoma
Curr Opin Oncol
Cited by (150)
Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study
2021, Journal of the American Academy of DermatologyTargeting kinases with thymoquinone: a molecular approach to cancer therapeutics
2020, Drug Discovery TodayNovel approaches for managing aged skin and nonmelanoma skin cancer
2020, Advanced Drug Delivery Reviews
Dr Fecher is currently affiliated with the Division of Hematology/Oncology, Department of Medicine, Indiana University, Indianapolis.
Supported by the Skin Disease Research Center at the University of Pennsylvania.
Disclosure: Dr Amaravadi is a consultant for and has received honoraria from Genentech. Dr Fecher is an investigator for Roche, Genentech, and GlaxoSmithKline, and has received research funding from those sources. Dr Schuchter is an investigator for Roche and GlaxoSmithKline, and has received grant funding from both sources. Drs Chu, Wanat, Miller, Brose, Seykora, and Rosenbach, Ms McGettigan, and Ms Giles have no conflicts of interest to declare.