Benefit of Binimetinib Addition to Encorafenib Confirmed in Melanoma
Binimetinib a BRAF inhibitor, improved objective response rate and progression-free survival among patients with BRAF-mutant melanoma.
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Binimetinib, a MEK inhibitor, plus encorafenib, a BRAF inhibitor, improved objective response rate (ORR) and progression-free survival (PFS) among patients with BRAF-mutant melanoma, which confirmed earlier findings with a higher encorafenib dose, according to research presented at the European Society of Medical Oncology (ESMO) 2017 Congress in Spain.1
Binimetinib (45 mg twice daily) plus encorafenib (400 mg once daily) improved PFS compared with vemurafenib or encorafenib (300 mg once daily) alone in part 1 of the phase 3 COLUMBUS trial. Part 2 of the trial sought to determine if this benefit was maintained at the control dose of encorafenib 300 mg.1
In part 2 of the COLUMBUS trial, patients with metastatic melanoma that harbored the BRAF V600 mutation were randomly assigned 3:1 to receive binimetinib (45 mg twice daily) plus encorafenib (300 mg once daily) or encorafenib (300 mg once daily) alone. Analysis of the encorafenib arm included data from the encorafenib arm from part 1 of the trial.
The ORR with the combination was 66% compared with 50% and 50% with encorafenib alone in the pooled data and part 2 arm only, respectively.
PFS was prolonged with the binimetinib and encorafenib combination, with a median of 12.9 months (95% CI, 10.1-14.0 months) compared with 9.2 months (95% CI, 7.4-11.0 months) from the encorafenib pooled data (hazard ratio [HR], 0.77; 95% CI, 0.61-0.97; P = .029) and 7.4 months (95 % CI, 5.6-9.2) in the encorafenib arm from part 2 only (HR, 0.57; 95% CI, 0.41-0.78; P < .001).
Discontinuation of the study due to adverse events (AEs) was similar among arms (10% to 12%), though more patients required dose modification due to AEs with encorafenib alone (69% pooled data and 63% part 2 only) compared with the combination (45%).
AEs that occurred less frequently with the combination compared with encorafenib alone included nausea, arthralgia, vomiting, myalgia, alopecia, headache, and extremity pain.
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According to the investigators, results from part 2 of the COLUMBUS trial confirm the benefit of the addition of binimetinib to encorafenib in terms of efficacy and safety.
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- Dummer R, Ascierto PA, Gogas H, et al. Results of COLUMBUS Part 2: a phase 3 trial of encorafenib (ENCO) plus binimetinib (BINI) versus ENCO in BRAF-mutant melanoma. Presented at: ESMO 2017 Congress; Madrid, Spain: September 8-12, 2017. Abstract 1215O.