Defining the Prognostic Significance of BRAF V600E in Early-Stage Colon Cancer: A Systematic Review and Meta-Analysis

Abstract

Background: BRAF mutations are found in 10% of colon cancers (CCs) and are associated with poor prognosis in metastatic disease. BRAF V600E predicts sensitivity to cetuximab + encorafenib in the metastatic setting. With new trials testing encorafenib-containing regimens for early-stage CC, we sought to characterize the clinical outcomes of early-stage BRAF V600E CC. Methods: We performed a systematic review and meta-analysis. Key inclusion criteria were a diagnosis of stage 2/3 BRAF V600E CC. Co-primary endpoints were overall survival (OS) and recurrence/disease-free survival (DFS). Meta-analysis was performed with a random-effects model incorporating sample size, hazard ratio (HR), and 95% confidence intervals (CIs). Results: A total of 206 studies underwent full-text review. Of these, six randomized controlled trials were included, comprising 6836 and 843 patients with wild-type (WT) and BRAF V600E, respectively. BRAF V600E was associated with inferior OS (HR 1.49, CI 1.21–1.75) and DFS (HR 1.17, CI 1.03–1.33). This finding remains in patients with microsatellite instability—low/stable or proficient mismatch repair (OS: HR 1.66, CI 1.36–2.02, DFS: HR 1.45, CI 1.22–1.72). Conclusions: BRAF V600E is associated with inferior prognoses compared to BRAF WT in early-stage CC. This finding will help optimize trial design for this population.