Real-World Safety of Anti-EGFR Antibodies: 20-Year Pharmacovigilance of Cetuximab and Panitumumab.

Background: Colorectal cancer remains a major contributor to global cancer-related mortality. Although EGFR-targeted monoclonal antibodies (cetuximab, panitumumab) have demonstrated efficacy in improving clinical outcomes, their associated adverse events underscore the need for enhanced prevention and management strategies. This study analyses real-world post-marketing data to enhance patient safety. Methods: The FDA Adverse Event Reporting System database served as the data source for this study, which centered on AEs related to cetuximab and panitumumab from 2004 to 2024. Standardized MedDRA queries are performed to fully search for AEs at the preferred term (PT) level. The analysis applied the reporting odds ratio (ROR) to identify AEs signals. The reliability of the findings was reinforced by employing multivariate logistic regression to handle confounders. Results: The analysis included 19,131 cetuximab primary suspect cases with 50,338 adverse events (AEs) and 9,448 panitumumab primary suspect cases with 30,061 AEs. The incidence of AEs for cetuximab in 24 organ systems and for panitumumab in 23 organ systems. Cetuximab had higher AE frequency in skin, vascular, and respiratory disorders, with the majority of skin-related AEs occurring within 15 days. Panitumumab showed stronger links to hypomagnesemia and hepatobiliary disorders, and and neurotoxicity, with skin AEs appearing around 28 days. Notably, panitumumab exhibited a higher risk of AEs compared to cetuximab and revealed a novel signal for hepatobiliary disorders. Conclusion: The study demonstrates substantial variations in the safety of cetuximab and panitumumab, emphasizing the need for tailored monitoring, prudent interchangeability, and management strategies in clinical practice. Future research should explore the underlying mechanisms and targeted interventions to improve patients' outcomes and quality of life.