Efficacy of targeted therapy versus immunotherapy in metastatic colorectal cancer: A systematic review and meta-analysis.

Abstract

e15593 Background: The management of metastatic colorectal cancer (mCRC) has evolved with the advent of targeted therapies and immunotherapy. While targeted therapies like EGFR and VEGF inhibitors are standard for RAS wild-type and angiogenic pathways, immune checkpoint inhibitors have demonstrated efficacy in microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. This meta-analysis compares the efficacy of targeted therapy versus immunotherapy in mCRC, focusing on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Methods: We performed a systematic search of PubMed, Embase, Cochrane Library, and clinical trial registries up to January 2025. Inclusion criteria were randomized controlled trials (RCTs) and cohort studies directly comparing targeted therapy (e.g., bevacizumab, cetuximab) and immunotherapy (e.g., pembrolizumab, nivolumab) in mCRC. Outcomes analyzed included PFS, OS, ORR, and treatment-related adverse events. Data were pooled using a random-effects model. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated with funnel plots. Results: A total of 15 studies (9 RCTs and 6 cohort studies) involving 6,824 patients met the inclusion criteria. Among MSI-H/dMMR patients, immunotherapy demonstrated superior OS (HR = 0.68, 95% CI: 0.54–0.85, p < 0.001) and ORR (48% vs. 22%, p < 0.01) compared to targeted therapy. In RAS wild-type patients treated with EGFR inhibitors, targeted therapy provided a modest PFS benefit (HR = 0.84, 95% CI: 0.72–0.97, p = 0.02). Subgroup analyses revealed higher toxicity rates in targeted therapy (grade 3–4 adverse events: 38% vs. 25%, p < 0.05). The overall quality of evidence was rated as high based on GRADE criteria. Conclusions: This meta-analysis highlights the superiority of immunotherapy in MSI-H/dMMR mCRC, while targeted therapies remain effective in RAS wild-type tumors. The results underscore the importance of molecular profiling in treatment selection. Future research should explore combination strategies and novel biomarkers to optimize outcomes in mCRC.