Survival Outcomes in Metastatic Colorectal Cancer Patients with BRAF Mutations Undergoing Targeted Chemotherapy: A Reconstructed Individual Patient Data Meta-Analysis of Randomized Controlled Trials

BRAF V600E-mutant metastatic colorectal cancer (mCRC) represents an aggressive molecular subtype associated with poor prognosis and limited response to conventional chemotherapy. Although multiple targeted strategies, including anti-vascular endothelial growth factor (VEGF), anti-epidermal growth factor receptor (EGFR), and BRAF-directed therapies, are used in clinical practice, their comparative effectiveness remains uncertain. We performed a reconstructed individual patient-data (IPD) meta-analysis of randomized controlled trials (RCTs) to evaluate survival outcomes across targeted therapeutic classes in BRAF-mutant mCRC.

A systematic search of PubMed, Embase, Scopus, and Cochrane databases was conducted through July 2025 to identify RCTs reporting survival outcomes for BRAF-mutant mCRC. Kaplan-Meier curves were digitized and IPD reconstructed using established methods. A one-stage meta-analysis using Cox proportional hazards models was performed to estimate pooled overall survival (OS) and progression-free survival (PFS). Models were adjusted for study-level covariates and clustering, with Bonferroni correction applied for multiple comparisons.