Part 2 of the study was initiated at the request of the US FDA to better understand the contribution of binimetinib to the combination therapy by comparing encorafenib 300 mg once daily plus binimetinib 45 mg twice daily with encorafenib 300 mg once daily alone. Results of part 2 will be published separately.
According to a commentary, these results have led to the approval of encorafenib plus binimetinib for BRAF-mutant advanced melanoma by the US FDA and by the European Medicines Agency. It notes that this combination is the third BRAF–MEK inhibitor combination approved for the same indication, which begs the question: which one is the best? It suggests that perhaps the combinations of vemurafenib plus cobimetinib, dabrafenib plus trametinib, and encorafenib plus binimetinib are so similar in terms of activity that the prescription decision will be made only on the basis of their toxicity profiles and reimbursement issues. It adds that an important piece of information that could help decide which treatment to use is quality-of-life data which are not yet available from the COLUMBUS trial. It concludes that the outcomes observed with encorafenib plus binimetinib provide good news for patients with advanced BRAF-mutant melanoma, but there is probably no need for additional novel BRAF–MEK inhibitor combinations. Resources from both the pharmaceutical industry and investigators should instead be invested in smarter clinical trial designs that can answer relevant clinical questions, such as whether sequencing of drugs is better than combination therapies, or defining the optimal duration of adjuvant treatment.