Introduction: Nearly 50% of melanomas harbor a BRAF mutation, and vemurafenib has shown a clinical response rate of approximately 50% and a median progression-free survival duration of ∼ 6 - 7 months in patients with V600 BRAF-mutant advanced melanoma. Based on a Phase III study demonstrating a survival advantage over dacarbazine, vemurafenib was approved by the regulatory agencies for the treatment of V600 BRAF-mutant advanced melanoma in 2011. Although vemurafenib does not induce life-threatening toxicity frequently associated with conventional chemotherapy. It is associated with other adverse events, particularly skin toxicities.
Areas covered: We discuss the mechanism of action, pharmacokinetics and pharmacodynamics, clinical efficacy, and safety profile of vemurafenib in patients with metastatic melanoma harboring a BRAF mutation. In particular, we describe in detail the skin toxicity of vemurafenib, including the development of keratoacanthoma and squamous cell carcinoma of the skin.
Expert opinion: Both preclinical and clinical investigations have shed light on our understanding of the skin toxicities associated with vemurafenib and have led to potential strategies for reducing the frequency of these adverse events. Further understanding of other associated toxicities could significantly improve the quality of life for patients undergoing treatment with vemurafenib or another BRAF inhibitor.