Dabrafenib plus trametinib vs encorafenib plus binimetinib in BRAF-mutant metastatic melanoma: a real-world propensity score-matched survival analysis.

Abstract

Encorafenib is a BRAF inhibitor with a pharmacodynamic profile distinct from that of dabrafenib, including a longer dissociation half-life that may enable more sustained BRAF inhibition. It has been hypothesized that this could translate into superior clinical efficacy. We aimed to determine whether encorafenib plus binimetinib is superior to dabrafenib plus trametinib in terms of clinical activity and outcomes. Patients were identified through the Danish Metastatic Melanoma Database, a national registry collecting prospective data on systemic treatments. We retrospectively retrieved baseline, treatment, and outcome data for patients with metastatic BRAF-mutant melanoma treated with encorafenib plus binimetinib or dabrafenib plus trametinib from 2017 to 2024. Both unmatched and propensity score-matched analyses were conducted to mitigate potential confounding. A total of 751 patients were included (422 dabrafenib plus trametinib, 329 encorafenib plus binimetinib). Baseline characteristics were balanced between groups. In the unmatched cohort, no statistically differences were observed between dabrafenib plus trametinib and encorafenib plus binimetinib in progression-free survival (PFS; median = 7.9 vs 8.0 months; hazard ratio [HR] = 0.99, P = .90), overall survival (median = 15.5 vs 15.4 months; HR = 0.91, P = .30), or melanoma-specific survival (median = 16.2 vs 15.7 months; HR = 0.94, P = .50). Propensity score-matched analyses confirmed these findings (PFS: HR = 1.05, P = .60; overall survival: HR = 0.922, P = .41; melanoma-specific survival: HR = 0.97, P = .74). Post hoc power analysis for detecting a 3-month survival difference was adequate for PFS (97.5%) but limited for overall survival (56.3%) and melanoma-specific survival (52.1%). We found no evidence that encorafenib plus binimetinib is superior to dabrafenib plus trametinib in metastatic melanoma. These findings suggest that the choice between these combinations should be guided by tolerability profiles and economic considerations rather than efficacy.