Discussion

Activating mutations in BRAF codon 600 are central drivers in aberrant constitutive mitogen-activated protein kinase (MAPK) activity and have been identified in 25% to 56% of malignant melanomas. 2-5 BRAFis that exhibit high specificity for V600-mutant BRAF relative to wild-type BRAF have demonstrated objective response rates of 50% to 60% in phase I-III clinical trials in metastatic melanoma; however, the development of treatment resistance commonly limits the durability of this response. 5 MEKis are also active in this disease, particularly whenBRAFV600 mutations are present. 6, 7 A recently reported study of combined BRAFi and MEKi therapy indicates that this combination can result in better clinical outcomes than monotherapy with either agent alone. 1