Abstract
BACKGROUND: Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab are extensively used in metastatic colorectal cancer therapy, their association with the risk of high grade infections remains unclear. OBJECTIVE: The purpose of this study was to systematically assess the risk of high grade infections and febrile neutropenia in colorectal cancer (CRC) patients treated with anti-EGFR monoclonal antibodies. METHODS: A systematic search was conducted in the PubMed, Embase, and Cochrane Library to include all randomized controlled trials comparing anti-EGFR therapy with control measures in the treatment of CRC up to 12 October 2025. Data on high grade infections and febrile neutropenia were extracted. As claimed by the heterogeneity (I²) results, random or fixed effects models were used to calculate the pooled incidence with its risk ratio (RR). RESULTS: A significantly elevated risk of high grade infection was associated with anti-EGFR therapy based on a meta-analysis of 10 randomized controlled trials (N = 7927). The incidence was 15.8% in the treatment group versus 10.2% in the control group, corresponding to a pooled RR of 1.49 (95% CI: 1.23-1.82, P < 0.001), which represents a 49% increase in risk. The analysis indicated moderate heterogeneity (I² = 43%). Sensitivity analyses confirmed that the association was robust. However, the difference in the risk of febrile neutropenia between the groups was not statistically significant (RR = 1.26, 95% CI: 0.98-1.63, P = 0.08). The funnel plot and Egger's test indicated the potential presence of publication bias. CONCLUSION: Treatment with anti-EGFR monoclonal antibodies (mAbs) notably augments the risk of high grade infections in CRC patients, but does not significantly raise the risk of febrile neutropenia. These findings suggest that enhanced monitoring and preventive management of infections are necessary when applying EGFR-targeted therapy in clinical practice.