BRAF-mutant Melanoma – The COLUMBUS Trial

Abstract

Support: No funding was received in the publication of this article. Melanoma represents a significant and increasing public health burden, and is the largest cause of skin cancer-related deaths. Approximately half of advanced (unresectable or metastatic) melanomas have a mutation in the BRAF gene, with V600E being the most common mutation, leading to the therapeutic use of BRAF inhibitors. However, the response rates with single-agent BRAF inhibitors are low, and therefore combined BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibition has been investigated. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma but has an increased incidence of adverse events. The encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS) trial was a two-part, randomised, open-label phase III study conducted at 162 hospitals in 28 countries, and investigated the efficacy and safety of encorafenib, a BRAF inhibitor, alone or in combination with binimetinib, a MEK inhibitor, versus vemurafenib in patients with advanced BRAF V600-mutant melanoma.