Contribution of MEK Inhibition to Combined BRAF/MEK Inhibitor Treatment in Advanced BRAF-Mutant Melanoma

Source: The Asco Post, August 2023

In part 2 of a phase III trial (COLUMBUS) reported in the Journal of Clinical Oncology, Paolo A. Ascierto, MD, and colleagues found evidence that MEK inhibition contributed to positive outcomes with combination BRAF/MEK inhibitor therapy in advanced BRAF V600–mutant melanoma.

Study Details
As stated by the investigators: “In COLUMBUS part 1, patients with advanced BRAF V600–mutant melanoma were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice a day (COMBO450), vemurafenib 960 mg twice daily, or encorafenib 300 mg once daily (ENCO300). As previously reported, COMBO450 improved progression-free survival … versus vemurafenib (part 1 primary endpoint) and ENCO300 (part 1 key secondary endpoint; not statistically significant). Part 2, requested by the U.S. [Food and Drug Administration] evaluated the contribution of binimetinib by maintaining the same encorafenib dosage in the combination (encorafenib 300 mg once daily plus binimetinib 45 mg twice daily [COMBO300]) and ENCO300 arms.”

In part 2, 344 patients from sites in 24 countries were randomly assigned 3:1 between March 2015 and November 2015 to receive COMBO300 (n = 258) or ENCO300 (n = 86). Analyses included the ENCO300 group of 194 patients from part 1, yielding a combined ENCO300 group of 280 patients. The major outcome measure in the current analysis was progression-free survival assessed by blinded independent review committee.