ABSTRACT
Introduction
Approximately 50% of patients with metastatic melanoma have mutations in BRAF. Based on the results of prior phase III trials, the combination of a BRAF inhibitor (BRAFi) and a MEK inhibitor (MEKi) is the standard of care in patients with BRAF-mutant metastatic melanoma.
Areas covered
The author summarizes the available data on binimetinib, a reversible inhibitor of the kinase activity of MEK1 and MEK2, in BRAF- and NRAS-mutated melanoma.
Expert opinion
With the advent of binimetinib and encorafenib, clinicians can choose between three BRAFi/MEKi combinations. Indirect comparison and a network meta-analysis suggest that binimetinib plus encorafenib is at least as active as the other two BRAFi/MEKi combinations and that safety is similar. The choice should be guided by the slightly different toxicity profile, local availability, and product experience. The optimal sequence of immunotherapy and BRAFi/MEKi in patients with BRAF-mutated tumors is unclear. As the response to BRAF/MEK inhibition is usually prompt and response to immunotherapy can be delayed, clinicians often choose a BRAFi/MEKi combination as first-line therapy in patients with rapidly evolving and threatening disease. Single-agent binimetinib almost doubled median progression-free survival when compared to dacarbazine in patients with NRAS-mutated melanoma.
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Article highlights
The combination of encorafinib and binimetinib significantly prolongs progression-free survival when compared to vemurafenib in patients with BRAF-mutated advanced melanoma.
This combination is the third combination showing improved outcome with the addition of a MEK inhibitor to a BRAF inhibitor as monotherapy.
Declaration of interest
P Specenier has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
One referee declares employment with Replimune Inc while another referee is on the speakers’ bureau for Array/Pfizer Inc. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.