Encorafenib Plus Binimetinib Versus Dabrafenib Plus Trametinib in First-Line for Patients With Metastatic Non-Small Cell Lung Cancer Harboring BRAF V600E Mutation: Matching Adjusted Indirect Comparison of Pharos and BRF113928

OBJECTIVES: Combination of BRAF and MEK inhibitors is a standard of care for BRAF V600E mutated NSCLC. Encorafenib and binimetinib combination (EncoBini) has recently shown meaningful clinical benefit in this population based on the single-arm Phase II PHAROS trial (NCT03915951). In order to assess the relative efficacy and safety of EncoBini vs. dabrafenib plus trametinib (DabraTrame) in first line, we conducted an unanchored matching-adjusted indirect comparison (MAIC) using patient-level data from PHAROS (cut-off of July 2023) and aggregated data from DabraTrame trial BRF113928 (NCT01336634) with a minimum of 5-year follow-up.

METHODS: All patients included in PHAROS met the eligibility criteria of BRF113928. In the MAIC, PHAROS patients were matched to DabraTrame trial baseline characteristics on ECOG performance status, smoking status, age, gender, race, histology, presence of brain metastases. Weighted Hazard proportional Cox and logistic regression models were fitted to estimate the relative efficacy of EncoBini vs DabraTrame for time to progression (assessed by independent radiographic review [PFS IRR]), overall survival [OS]), overall response rate [ORR IRR], and adverse events [AE].

RESULTS: After matching, characteristics in the weighted PHAROS and in BRF113928 populations were perfectly aligned. The MAIC resulted in an effective sample size of 44 out of 59 in PHAROS (vs 36 patients in BRF113928). Adjusted indirect comparison showed that EncoBini was numerically superior to DabraTrame for ORR A statistically significant reduction in serious AE rate with Encobini was observed (OR=0.34 [0.14;0.81]). Unadjusted analyses were performed resulting in consistent findings.

CONCLUSIONS: This MAIC suggest EncoBini combination improved clinical outcomes with Encobini compared with DabraTrame in 1^st line in adult patients with BRAFV600E mutated metastatic NSCLC along with a more manageable safety profile.