Evolving Ocular Safety Signals of EGFR Inhibitors: A FAERS Disproportionality Analysis of Amivantamab, Mobocertinib, and Classic Agents

Abstract Background Epidermal Growth Factor Receptor (EGFR) inhibitors, while effective in oncology, are associated with under-characterized ocular adverse events (AEs). Prior studies have been limited in scope, lacking a comprehensive, class-wide analysis of the full spectrum of ocular toxicity, particularly for newer agents. Methods We conducted a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) (2001-2025). Twelve EGFR-targeted agents were evaluated against a pre-specified set of ocular MedDRA Preferred Terms. To ensure robust signal detection, a significant association was defined by ≥3 co-reported cases, a Proportional Reporting Ratio (PRR) ≥2.0, and a false-discovery-rate adjusted p-value <0.05. Results Among 6,976,462 drug-event combinations, 20 met all signal criteria for Eyelash Abnormalities, Ocular Surface Disease, or Vision-Threatening and Intraocular Events. Trichomegaly demonstrated extreme disproportionality (e.g., panitumumab PRR= 465.3, 95% Confidence Interval [CI], 247.7-874.3). A consistent pattern of ocular surface toxicity (conjunctivitis, keratitis, blepharitis) was observed across multiple tyrosine kinase inhibitors and monoclonal antibodies, indicating a class-wide effect. Signals for serious events included corneal perforation (erlotinib, n= 7, PRR=13.9, 95% CI= 6.6-29.4) and optic neuropathy (erlotinib, n= 6, PRR= 2.9, 95% CI= 1.3-6.4). Conclusion This analysis confirms a strong, class-wide signal for ocular toxicity across the spectrum of EGFR inhibitors, from characteristic eyelid changes to sight-threatening complications. These findings underscore the necessity for proactive ophthalmologic monitoring, including baseline assessment, in patients receiving these therapies to preserve vision and maintain quality of life during cancer treatment.