Evolving Ocular Safety Signals of EGFR Inhibitors: A FAERS Disproportionality Analysis of Amivantamab, Mobocertinib, and Classic Agents
Abstract/Description/Artist Statement
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.
Faculty Advisor/Mentor
Thomas J Joly
Faculty Advisor/Mentor Email
tjoly@cvphealth.com
Faculty Advisor/Mentor Department
Ophthalmology
College/School Affiliation
Eastern Virginia School of Medicine
Student Level Group
Medical
Presentation Type
Poster
Evolving Ocular Safety Signals of EGFR Inhibitors: A FAERS Disproportionality Analysis of Amivantamab, Mobocertinib, and Classic Agents
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.