Postmarketing Safety Signals of Antibody–Drug Conjugates Compared to Traditional Therapies in Breast Cancer: A FAERS-Based Study

Objective: Breast cancer is the most common malignancy in women. Antibody-drug conjugates (ADCs) have improved treatment, but real-world safety data are limited. This study evaluated ADC safety profiles using pharmacovigilance data. Methods: We analyzed 26,368 AE reports from 22,855,420 FAERS entries (2013–2024) for four breast cancer ADCs: trastuzumab emtansine, trastuzumab deruxtecan, sacituzumab govitecan, and datopotamab deruxtecan. Safety signals were identified using ROR, PRR, BCPNN, and MGPS. AEs were categorized by system organ class, and subgroup analyses compared HER2- and TROP2-targeting ADCs. Results: Key AE signals included interstitial lung disease (ILD), Clostridium difficile infections, and weight changes. HER2-targeting ADCs were linked to ILD and hematologic toxicity, while TROP2-targeting agents had more gastrointestinal complications. Additional signals involved social circumstances (e.g., care dependency) and organ-specific toxicities, revealing divergent ADC toxicity profiles. Conclusion: This study highlights distinct safety profiles for HER2- and TROP2-targeting ADCs, underscoring the need for tailored monitoring. Continuous surveillance and research into mechanisms and comparative safety are crucial for optimizing breast cancer treatment.