Encorafenib plus binimetinib versus dabrafenib plus trametinib for the first-line treatment of patients with BRAF-mutant metastatic non-small cell lung cancer: a matching-adjusted indirect treatment comparison.

[BACKGROUND] The first-line (1L) standard of care for B-Raf proto-oncogene (BRAF)-mutant metastatic non-small cell lung cancer is BRAF inhibitor dabrafenib with MEK inhibitor trametinib (D + T). Combination therapy with encorafenib and binimetinib (E + B) has recently demonstrated clinical benefit in this setting in the single-arm, phase II PHAROS trial. We evaluated the relative efficacy and safety of E + B versus D + T in 1L using an unanchored matching-adjusted indirect comparison.

[MATERIAL AND METHODS] Individual patient data for E + B from PHAROS were matched on validated adjustment factors to aggregate data for D + T from Study BRF113928. The relative efficacy and safety of E + B versus D + T were assessed using weighted Cox proportional hazards models for overall survival and progression-free survival (PFS) and logistic regression models for objective response rate, grade 3-4 adverse events, serious adverse events (SAEs) and treatment discontinuation.

[RESULTS] Compared with D + T, E + B was associated with a statistically significant improvement in PFS [hazard ratio (HR) = 0.47; 95% CI 0.26-0.85; P = 0.01] and non-significant improvements in overall survival (HR = 0.55; 95% CI 0.30-1.01; P = 0.06) and objective response rate [odds ratio (OR) = 1.81; 95% CI 0.71-4.59, P = 0.21]. E + B was also associated with a statistically significant reduction in SAEs versus D + T (OR = 0.35; 95% CI 0.14-0.85; P = 0.02); reductions in grade 3-4 adverse events (OR = 0.93; 95% CI 0.37-2.32; P = 0.87) and treatment discontinuations (OR = 0.71; 95% CI 0.24-2.06; P = 0.53) were not statistically significant. Unadjusted indirect treatment comparisons and sensitivity analysis results were consistent with matching-adjusted indirect comparison findings.

[CONCLUSIONS] This analysis suggests that E + B was associated with statistically significantly longer PFS and fewer SAEs compared with D + T, and may offer an alternative option for the 1L treatment of BRAF-mutant metastatic non-small cell lung cancer.