R. Anforth ,T. Blumetti , A. Mohd-Affandi , P. Fernandez-Peñas
Introduction: BRAF inhibitors (BRAFi) will soon become
the fi rst line therapy for BRAF mutant stage IV metastatic
melanoma. These agents target a BRAF kinase mutation
found in 50% of melanomas called V600E, which leads to
activation of the MAPK pathway. Currently there are
2 BRAFis, Vemurafenib (Roche) that has recently been
approved by the FDA and GSK2118436 (GlaxoSmithKline),
which is currently in phase 3 clinical trials. The main drawback
of these agents is the development of cutaneous squa-
mous cell carcinomas (CuSCC).
Methods: Patients enrolled in BRAFi clinical trials at Westmead Hospital, Sydney, who developed large numbers of hyperkeratotic papules (verrucal keratosis & CuSCC) (≥20) were offered treatment with acitretin. Baseline number of lesions was noted prior to its commencement and again at each subsequent visit. Patients were started at 10 mg daily and titrated to a maximum dose of 25 mg daily depending on their response.
Results: Five patients on GSK2118436 and 1 patient on Vemurafenib commenced acitretin. All six noted a reduction in the number and size of lesions up to one month after commencing the treatment. One patient went from developing up to 9 new lesions each visit to no lesions 2 months post acitretin. A second patient went from having an uncountable number of lesions, to no new lesions after only 3 weeks of taking acitretin.
Discussion: The use of acitretin as a chemopreventative agent for the development of benign hyperkeratotic lesions and CuSCC triggered by BRAFi’s is still in the preliminary stage. It has been used previously in immunosuppressed patients who have received a solid organ transplant and have been shown to reduce the incidence of non-melanoma skin cancer . In this case series, a signifi cant reduction in benign and malignant keratinocytic lesions was noted on commencement of acitretin. This led to a reduction in the number of biopsies and excisions required and an improvement in patients’ anxiety and quality of life.