Gender Differences in EGFR-TKI-Related Adverse Events: A Pharmacovigilance Study Based on the FAERS Database

Introduction Based on the FAERS database, this retrospective pharmacovigilance study analyzed gender-based reporting signals for adverse events associated with three EGFR-TKIs. Methods Adverse drug reaction (ADR) data were collected from the FAERS database for three drugs: gefitinib (Q4 2003–Q4 2024), afatinib (Q4 2013–Q4 2024), and osimertinib (Q4 2015–Q4 2024). Reporting odds ratio (ROR) was used to detect the disproportionality signals and to assess the presence of gender differences in reporting. Results A total of 6,618 adverse events were reported for gefitinib (3,917 in females and 2,701 in males), 5,073 for afatinib (3,110 in females and 1,963 in males), and 18,415 for osimertinib (12,007 in females and 6,408 in males). For all three medications, the annual number of adverse drug event (ADE) reports was higher in females than in males. The ROR value and number of ADE reports under the SOC distribution indicated predominant reporting signals of skin and gastrointestinal adverse reactions. Gender-specific analysis of skin and gastrointestinal ADEs revealed that: (i) Gefitinib showed higher reporting signals for intestinal pneumatosis and skin ulcers in females; (ii) Afatinib showed higher reporting signals for acneiform dermatitis and oral pain in females, while males showed a higher reporting frequency of stomatitis and glossitis; (iii) Osimertinib showed higher reporting signals for diarrhea in females. These observed reporting disparities generate hypotheses regarding potential contributing factors, such as gender-based differences in hormone levels, gastrointestinal tract anatomy, and skin barrier function. Conclusions This pharmacovigilance analysis suggests the presence of sex-based reporting disparities in adverse event reports for three EGFR-TKIs. Females showed overall stronger reporting signals, with notable differences observed in specific skin and gastrointestinal events. Although the analysis has certain limitations, these findings generate hypotheses to inform future focused investigations.