Cardiovascular adverse events in patients with HER2-positive breast cancer treated with trastuzumab-drug conjugates : a Bayesian disproportional real world study for signal detection leveraging the FDA Adverse Event Reporting System (FAERS)

Background The cardiovascular risk profiles of trastuzumab drug conjugates (T-DCs) in the treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer are uncertain. This study analyzed real-world adverse events data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to investigate the association between T-DCs and major adverse cardiovascular events (MACE).Methods We searched the FAERS database for reports of cardiovascular adverse events in patients with HER2-positive breast cancer receiving trastuzumab, ado-trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-Dxd). The primary endpoint was MACE and the secondary endpoint was other cardiovascular events.Results Between January 2015 and April 2024, out of 135,226 drug-adverse event pairs analyzed, 8,497 were cardiovascular events, with 4,457 classified as MACE and 4,040 as other cardiovascular events.Trastuzumab reached pharmacovigilance for MACE (ROR = 1.39, 95%CI:1.30-1.49, IC025 = 0.25), while neither T-DM1 (ROR = 0.78, 95%CI: 0.69-0.88, IC025=-0.51) nor T-Dxd (ROR = 0.63, 95%CI:0.52-0.76, IC025=-0.93) reached MACE-related pharmacovigilance. Among MACE, stroke linked to T-DM1 (ROR = 1.86, 95%CI:1.42-2.43, IC025 = 0.35) and T-Dxd (ROR = 2.44, 95%CI:1.68-3.56, IC025 = 0.57) both reached pharmacovigilance in younger patients (<65 years). Proportionate analysis showed age and weight were the two key factors contributing to the occurrence of T-DCs induced MACE.Conclusion HER2-positive breast cancer patients receiving T-DCs require additional cardiac monitoring, particularly for stroke in younger patients.