The following is a summary of “Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of BRAF-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial,” published in the October 2023 issue of Oncology by Ascierto, et al.
For a study, researchers sought to assess the effectiveness and safety of the combination therapy involving encorafenib and binimetinib in patients with advanced BRAFV600-mutant melanoma, specifically investigating the contribution of binimetinib.
In the study’s first part (COLUMBUS part 1), patients were randomly allocated in a 1:1:1 ratio to one of three groups: encorafenib 450 mg once daily plus binimetinib 45 mg twice daily (COMBO450), vemurafenib 960 mg twice daily, or encorafenib 300 mg once daily (ENCO300). The results of part 1 demonstrated that COMBO450 improved progression-free survival (PFS) compared to vemurafenib (the primary endpoint) and showed an improvement in PFS compared to ENCO300 (a key secondary endpoint, although not statistically significant). In response to a request from the US Food and Drug Administration (FDA), part 2 of the study evaluated the contribution of binimetinib while maintaining the same dosage of encorafenib in the combination. This part included two arms: encorafenib 300 mg once daily plus binimetinib 45 mg twice daily (COMBO300) and ENCO300.
Part 2 of the study involved 258 patients receiving COMBO300 and 86 patients receiving ENCO300. Per protocol, data from ENCO300 arms in both parts 1 and 2 were combined (total n = 280). The median follow-up for ENCO300 was 40.8 months (part 1) and 57.1 months (part 2). Median PFS was 12.9 months for COMBO300 versus 9.2 months for ENCO300 (parts 1 and 2 combined) and 7.4 months for ENCO300 (part 2). The hazard ratio for COMBO300 versus ENCO300 (parts 1 and 2) was 0.74, with a statistically significant P-value of 0.003. The overall response rate (ORR) was 68% (62 to 74) for COMBO300 and 51% (45 to 57) for ENCO300 (parts 1 and 2 combined). Additionally, COMBO300 demonstrated better relative dose intensity and fewer grade 3/4 adverse events than ENCO300.
The study concluded that the combination therapy, COMBO300, offered improvements in PFS, ORR, and safety compared to ENCO300, highlighting the significant contribution of binimetinib to the therapy’s effectiveness and safety.
Source: ascopubs.org/doi/full/10.1200/JCO.22.02322
