Treatment with the combination of the MEK inhibitor binimetinib and the BRAF inhibitor encorafenib resulted in a superior progression-free survival for patients with advanced, unresectable BRAF-mutated melanoma compared with treatment with encorafenib alone.
Treatment with the combination of the MEK inhibitor binimetinib and the BRAF inhibitor encorafenib resulted in superior progression-free survival for patients with advanced, unresectable BRAF-mutated melanoma compared with treatment with encorafenib alone, according to a press release from Array BioPharma.
The results were from part 2 of the phase III COLUMBUS trial evaluating the drug combination. COLUMBUS was a two-part study that evaluated the combination of binimetinib plus encorafenib with vemurafenib alone and encorafenib alone. The study included 921 patients with locally advanced, unresectable, or metastatic melanoma positive for the BRAF V600 mutation.
In part 1 of the study, 577 patients were randomly assigned to 45-mg binimetinib plus 450-mg encorafenib, 300-mg encorafenib alone, or 960-mg vemurafenib alone. The primary endpoint was progression-free survival of the combination compared with vemurafenib alone. In part 2 of the study, 344 patients were randomly assigned 3:1 to 45-mg binimetinib plus 300-mg encorafenib or 300-mg encorafenib alone. This was designed to provide additional information about the contribution of binimetinib to the combination treatment.
Results from part 1 were presented at the Society for Melanoma Research Annual Congress in late 2016 by Keith T. Flaherty, MD, director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital, Boston. In part 1, patients assigned to treatment with the combination had a median progression-free survival of 14.9 months compared with 7.3 months for patients treated with vemurafenib alone (hazard ratio [HR], 0.54; 95% CI, 0.41–0.71; P < .001). In addition, patients assigned to binimetinib/encorafenib had an improved overall response rate compared with vemurafenib alone (63% vs 40%).
Results from part 2 are consistent with those from part 1. Patients assigned to the drug combination had a median progression-free survival of 12.9 months compared with 9.2 months for patients treated with encorafenib monotherapy (HR, 0.77; 95% CI, 0.61–0.97; P = .029).
According to the press release, the combination was generally well tolerated in both parts of the study. In part 1, grade 3/4 adverse events that occurred in more than 5% of patients receiving the combination included increased gamma-glutamyltransferase, increased blood creatine phosphokinase, and hypertension. The incidence of adverse events of special interest, for patients receiving the 450-mg combination included: rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%), and photosensitivity (5%). Adverse events were similar in both parts of the trial.
“The totality of the COLUMBUS results, including estimated progression-free survival, objective response rate, dose intensity, and tolerability of the combination, provide a strong and consistent theme across multiple endpoints, underscoring the promise of binimetinib plus encorafenib as an attractive treatment option for patients diagnosed with BRAF-mutant melanoma,” said Flaherty, in the press release.