BRAF and metastatic melanoma: In 2018, the third combination of BRAF and MEK inhibitors—encorafenib and binimetinib—were approved for unresectable or metastatic melanoma based on the result of the COLUMBUS trial.43 The results of this phase 3 study found the median overall survival of the group receiving combination therapy to be 33.6 months compared with 16.7 months for vemurafenib (HR, 0.54 [95% CI, 0.40-0.71]).