Encorafenib with binimetinib may be a promising combination for patients with BRAF­-mutant melanoma, according to research published in The Lancet Oncology.1

Up to half of patients with melanoma have a BRAFV600 mutation, which can be treated effectively with BRAF or MEK inhibitors including vemurafenib, though treatment resistance almost always develops, often via MAPK pathway reactivation. Encorafenib has, however, shown preclinical activity in tissues with activated MAPK pathways.

For the randomized, open-label phase 3 COLUMBUS trial (ClinicalTrials.gov Identifier: NCT01909453), researchers enrolled 1345 patients with locally advanced, unresectable, or metastatic melanoma with a BRAFV600 mutation to receive encorafenib with binimetinib (192 patients), encorafenib monotherapy (194 patients), or vemurafenib (191 patients). The median age in the encorafenib with binimetinib, encorafenib, and vemurafenib groups was 57, 54, and 56 years, respectively, most patients in all groups had stage IV disease, and about a third of patients in each group had received prior immunotherapy.

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The median follow-up was 16.7 months in the encorafenib plus binimetinib group, 16.6 months in the encorafenib group, and 14.4 months in the vemurafenib group. The complete response rates by central review were 8%, 5%, and 6% in the combination, encorafenib, and vemurafenib groups, respectively; 55%, 45%, and 35% of patients had a partial response, 63%, 51%, and 40% had an overall response, and the disease control rates were 92%, 84%, and 82%, respectively.

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The median progression-free survival by central review was 14.9 months in the combination group, 9.6 months in the encorafenib group, and 7.3 months in the vemurafenib group. The number of deaths was, however, similar during treatment/within 30 days after last dose among the 3 groups.

Grade 3 to 4 adverse events that occurred in at least 5% of patients included blood creatine phosphokinase increase (7%), anemia (5%), γ-glutamyltransferase increase (9%), alanine aminotransferase increase (5%), and hypertension (6%) in the combination group, vomiting (5%), arthralgia (9%), myalgia (10%), and palmoplantar erythrodysesthesia syndrome (14%) in the encorafenib group, and arthralgia (6%) in the binimetinib group.

One death possibly related to treatment was noted in the combination group.

The authors concluded that “results of the COLUMBUS study show that encorafenib plus binimetinib improved progression-free survival compared with vemurafenib and appears to have an improved tolerability profile compared with encorafenib or vemurafenib.”


  1. Dummer R, Ascierto PA, Gogas HJ, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018 Mar 22. doi: 10.1016/S1470-2045(18)30142-6 [Epub ahead of print]