Managing Side Effects of Vemurafenib Therapy for Advanced Melanoma

Somatic point mutations in the BRAF gene have been found in approximately 50% of melanomas. BRAF(V600E), the most common mutation, results in the constitutive activation of BRAF(V600E) kinase, sustaining MAPK signaling and perpetuating cell growth. This groundbreaking discovery led to the clinical development of vemurafenib, a selective BRAF inhibitor. Vemurafenib has been approved for the treatment of patients with BRAF(V600E)-positive unresectable or metastatic melanoma based on survival benefit demonstrated in a randomized phase III study. The current approved dosing schedule of vemurafenib is 960 mg orally twice a day until disease progression or unacceptable toxicity. Vemurafenib is well tolerated, with the most common adverse effects including skin reactions, photosensitivity, headache, and arthralgia. Active research is ongoing to expand the utility of vemurafenib into the adjuvant setting and to circumvent rapid emergence of drug resistance.