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Life sciences · Review
Journal of Gastrointestinal Cancer · October 30, 2026
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Abstract Background 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. Methods 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. Results Eighteen RCTs comprising 11,931 participants were included. Pooled median OS was 22.3 months for BRAF -directed regimens, 17.1 months for VEGF -targeted therapy, and 10.1 months for EGFR-directed therapy across studies evaluating first-line therapy. Across first-line studies, BRAF inhibitor directed regimen was associated with significantly improved OS compared with EGFR inhibition (HR 0.43, 95% CI 0.31–0.60; P < 0.001) and improved PFS (HR 0.47, 95% CI 0.42–0.53; P < 0.001). VEGF inhibition also demonstrated superior OS compared with EGFR inhibition (HR 0.56, 95% CI 0.38–0.81; p < 0.001). EGFR -directed regimen consistently demonstrated the poorest survival outcomes across analyses. Discussion In this reconstructed IPD meta-analysis, BRAF -directed therapies were associated with the most favourable survival outcomes, whereas EGFR directed regimen demonstrated limited clinical benefit in BRAF -mutant mCRC. These results highlight the importance of biologically aligned pathway-targeted therapy and provide comparative evidence to inform treatment selection in this aggressive molecular subtype.