Encorafenib and Binimetinib Receive FDA Approval for Unresectable or Stage 4 Melanoma

On 27 June 2018, the United States Food and Drug Administration FDA approved, for patients with BRAF V600E or V600K mutation-positive, unresectable or metastatic (stage 4) melanoma, the combination of encorafenib and binimetinib (Braftovi and Mektovi).

Approval was based on BRAF V600E or V600K mutation-positive, unresectable or metastatic melanoma in 577 patients in COLUMBUS, a randomized, active-controlled, open-label, multicenter clinical trial. The COLOMBUS study was also one of the most notable presentations at ASCO 2018.

Patients were divided into three groups:

• The first received binimetinib 45 mg twice daily and encorafenib 450 mg once daily,
• The second received encorafenib 300 mg once daily, and
• The third received vemurafenib 960 mg twice daily.

Treatment continued until disease progression or unacceptable side effects.

The primary efficacy endpoint was progression-free survival (the duration of disease control with treatment).

According to the Study Results;

• Median progression-free survival was 14.9 months with binimetinib plus encorafenib and 7.3 months with vemurafenib alone.
• This doublet reduced the risk of disease progression by %46 compared with standard vemurafenib treatment.
• Overall response rates were %63 and %40, respectively, and median response durations were 16.6 months and 12.3 months, respectively.
• Other comparisons between treatment arms showed no significant differences.

The most common (≥25%) side effects in combination-treated patients were fatigue, nausea, diarrhea, vomiting, abdominal pain and arthralgia. Treatment was discontinued because of side effects in % 5 of combination-treated patients; the most common reasons were bleeding and headaches.

Recommended doses: binimetinib 45 mg twice daily and encorafenib 450 mg once daily.

In conclusion, encorafenib and binimetinib have entered clinical practice as a new combination for BRAF-positive melanoma. Compared with previously approved combinationsfor this diagnosis, it appears more effective, although no such comparative study exists yet. It also appears more advantageous in terms of side effects.