Latest melanoma drug approvals: encorafenib plus binimetinib

New drug combination: encorafenib plus binimetinib for BRAF-mutant metastatic melanoma

Another milestone in the treatment of BRAFV600-mutant metastatic melanoma was marked by the newly approved drug combination of encorafenib plus binimetinib [Braftovi and Mektovi, by Array BioPharma Inc; approved by U.S. Food & Drug Administration (FDA) on June 27, 2018].

The dual targeting of the hyper-activated MAPK pathway by encorafenib (which blocks the signaling pathway of the V600-mutated BRAF molecule) and by binimetinib (which targets the activity of MEK in order to block the signaling from the V600-mutated BRAF molecule in coordination with the MEK molecule) is expected to improve therapy efficacy and to bring greater benefit to melanoma patients.

The drug combination was approved to treat unresectable stage III and stage IV melanoma patients with the V600E or V600K mutation in the BRAF gene.

Study outcomes

The approval was based on the open-label, multicenter COLUMBUS trial (NCT01909453) with 577 enrolled metastatic melanoma patients from 162 sites in 28 countries. Two MELGEN research sites were among the participating centers: the Department of Dermatology at the University Hospital Zurich (Switzerland) lead by Prof. Reinhard Dummer who was also the lead author of the publication, and the Department of Dermatology at the University Hospital of Essen (Germany) lead by Prof. Dirk Schadendorf.

In this trial, patients were randomized 1:1:1 to receive 450 mg encorafenib once daily plus 45 mg binimetinib twice daily, 300 mg encorafenib once daily, or 960 mg vemurafenib twice daily.

The efficacy measure of the trial was progression-free survival (PFS) by blinded independent central review. According to the research results, the median PFS was 14.9 months in the combination arm (patients receiving encorafenib plus binimetinib) vs. 7.3 months in the vemurafenib monotherapy arm (hazard ratio 0.54, 95% CI: 0.41-0.71, P<0.0001) vs. 9·6 months in the encorafenib group (hazard ratio 0.75, 95% CI 0.56– 1.00, two-sided P=0.051). The overall response rates were 63% for the combination arm (patients receiving encorafenib plus binimetinib) and 40% for the vemurafenib monotherapy arm, with median response duration of 16.6 months vs. 12.3 months, respectively. The overall response rate of the encorafenib monotherapy arm was 51% with 14.9 months of median response duration.

The FDA also granted approval of the THxID BRAF Kit (bioMérieux) as a companion diagnostic test for these drugs.

References:

https://www.fda.gov/

https://clinicaltrials.gov/

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 19:603-615, 2018. https://doi.org/10.1016/S1470-2045(18)30142-6

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