S316 Efficacy and Safety of Sintilimab (PD-1 Inhibitor) Combined With Anti-VEGF Therapy as Neoadjuvant Treatment in Colorectal Cancer: A Systematic Review and Proportional Meta-Analysis

Introduction: Metastatic colorectal cancer (mCRC) remains a major contributor to cancer mortality, particularly in RAS-mutant and microsatellite-stable (MSS) tumors, which respond poorly to immunotherapy. Combining PD-1 inhibitors like sintilimab with anti-vascular endothelial growth factor (VEGF) agents may enhance immune response by improving T-cell infiltration and vascular normalization. This study evaluates the efficacy and safety of this combination as neoadjuvant therapy in colorectal cancer. Methods: A systematic search of PubMed, Embase, and Cochrane was conducted for clinical trials published up to April 3, 2025, assessing sintilimab with anti-VEGF agents in neoadjuvant colorectal cancer treatment. Primary outcomes included adverse events (AEs), grade ≥3 AEs, progression-free survival (PFS), objective response rate (ORR), and stable disease (SD). Random-effects meta-analysis and leave-one-out sensitivity analysis were performed using R Studio. Results: Four trials (205 patients) were included. One-year PFS was 25% (95% CI: 9%–45%) with high heterogeneity (I² = 82.1%), resolved to 0% after excluding Liu 2025. Two-year PFS was 9% (95% CI: 5%–14%) with no heterogeneity. ORR was 55% (95% CI: 32%–76%; I² = 89.3%), dropping to 45.4% upon omitting Guo 2023. Stable disease was 42% (95% CI: 25%–60%; I² = 82.4%), reduced to 58.0% excluding Guo 2023. AEs occurred in 90% (95% CI: 65%–100%; I² = 94.0%), mainly influenced by Wang 2025 (I² dropped to 25.4%). Grade ≥3 AEs were 21% (95% CI: 3%–48%; I² = 92.4%), lowered to 9% (95% CI: 5%–15%) upon excluding Guo 2023. Conclusion: Neoadjuvant sintilimab plus anti-VEGF therapy demonstrates modest efficacy and manageable toxicity in colorectal cancer. High heterogeneity underscores the need for standardized approaches and biomarker-driven trials, particularly for MSS/RAS-mutant subgroups.