Real-world pharmacovigilance signals of antibody-drug conjugates: reporting patterns by payload, linker, target, and sex in FAERS.

Antibody-drug conjugates (ADCs) have transformed cancer therapy by delivering potent cytotoxic agents directly to tumor cells, yet their complex structure creates unique safety challenges. This retrospective pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) database from 2004Q1 to 2025Q4 to characterize adverse-event reporting patterns of 15 approved ADCs across 100,536 ADC-PT-report records derived from 34,041 unique FAERS reports. Using disproportionality algorithms, we identified heterogeneous adverse-event reporting patterns across ADCs grouped by payload, linker, and antibody target. Signals for peripheral neuropathy were frequently observed among microtubule inhibitor-based ADCs, whereas ILD signals were prominent among deruxtecan-containing ADCs. Cardiac-event signals were also observed among HER2-targeted ADCs, consistent with established HER2-related safety concerns. Notably, these associations should be interpreted as disproportionality signals generating mechanistic hypotheses rather than causal inferences. Sex-stratified analyses identified differences in reporting odds between female and male reports for several hematological and neuropathic events. These descriptive patterns may reflect differences in indication, ADC use, patient characteristics, and reporting practices rather than biological susceptibility. Time-to-onset was generally early among eligible reports, whereas T-DXd-associated ILD showed wide temporal dispersion (median, 62 days; Q1, 14.25 days; Q3, 166 days), with 22.8% of eligible reports occurring more than 180 days after treatment initiation. These findings identify reporting patterns that are consistent with established ADC pharmacology and generate hypotheses regarding possible structural correlates of adverse-event reporting. However, these associations do not establish independent effects of individual structural components or causal mechanisms. These findings provide a compelling rationale for future prospective studies and real-world cohort validation to explore tailored safety management in ADC therapies.