On June 27, 2018, the U.S. Food and Drug Administration (FDA) approved the combination regimen of Binimetinib and Encorafenib for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test.
Clinical Trials
This approval was based on a randomized, active-controlled, open-label, multicenter clinical trial known as COLUMBUS (Trial ID: NCT01909453). The trial enrolled 577 patients with unresectable or metastatic melanoma who tested positive for BRAF V600E or V600K mutations. Patients were randomized (1:1:1) to receive one of three treatment regimens: Binimetinib 45 mg orally twice daily plus Encorafenib 450 mg orally once daily; Encorafenib 300 mg orally once daily; or Vemurafenib 960 mg orally twice daily. Treatment continued until disease progression or unacceptable toxicity occurred.
The primary efficacy endpoint was progression-free survival (PFS), as assessed by a blinded independent central review using RECIST 1.1 criteria. The results demonstrated that the median PFS for patients treated with the combination of Binimetinib and Encorafenib was 14.9 months, compared to 7.3 months for the group receiving Vemurafenib monotherapy (Hazard Ratio [HR] 0.54; 95% Confidence Interval [CI]: 0.41 to 0.71; p < 0.0001). The objective response rate (ORR), as assessed by the central review committee, was 63% in the combination therapy group and 40% in the monotherapy group. The median duration of response (DOR) was 16.6 months and 12.3 months, respectively.
Common Adverse Reactions
Among patients receiving combination therapy, the most common adverse reactions (incidence ≥25%) included fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia. The proportion of patients who discontinued treatment due to adverse reactions was 5% in the combination therapy group; the most common reasons for discontinuation were hemorrhage and headache.
Recommended Dosage
The recommended dosage is 45 mg of Binimetinib taken orally twice daily, and 450 mg of Encorafenib taken orally once daily.
