Post-marketing safety surveillance of EGFR-targeted agents and disseminated intravascular coagulation risk: a disproportionality analysis based on the FDA Adverse Event Reporting System.

Abstract

Introduction: The epidermal growth factor receptor (EGFR) serves as a principal therapeutic target in oncology, with EGFR inhibitors representing essential agents in cancer treatment. Although thrombotic complications related to EGFR inhibitors have been reported in the literature, the evidence remains insufficient. Notably, EGFR inhibitor-associated disseminated intravascular coagulation (DIC) constitutes a potentially fatal condition that currently lacks comprehensive systematic investigation.

Aim: To systematically assess the signal and clinical characteristics of DIC potentially associated with EGFR inhibitors using pharmacovigilance data.

Method: Individual case safety reports (ICSRs) from the FDA Adverse Event Reporting System (FAERS) were extracted, with the 11 currently approved EGFR inhibitors designated as the primary suspect agents. Each drug's data was extracted from the initial approval date (or January 1, 2004, if approved prior to 2004) to December 31, 2024. After deduplication, disproportionality analyses were performed using four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Positive and negative controls were used to evaluate potential reporting bias.

Results: In FAERS, 104 ICSRs of DIC potentially associated with EGFR inhibitors were identified, of which 64 (61.54%) were fatal. Healthcare professionals accounted for the predominant proportion (82.69%) of ICSR submissions. All seven drugs with reports-cetuximab, panitumumab, gefitinib, erlotinib, afatinib, osimertinib and lapatinib-generated significant disproportionality signals. Cetuximab and gefitinib displayed the strongest disproportionality signals. ICSRs were predominantly reported from Asia, with Japan accounting for 43 ICSRs (41.35%). The median patient age was 68 years, with a balanced gender distribution. Non-small cell lung cancer (NSCLC) was the primary indication (24.04%).

Conclusion:  DIC may represent a pharmacovigilance signal associated with EGFR inhibitors, and may exhibit a potential class effect. Further clinical validation is required to establish causality. Proactive monitoring for DIC in patients receiving EGFR inhibitors is recommended.