Pharmacovigilance study and development of a clinical decision flowchart for personalized selection of trastuzumab, T-DXd, and T-DM1 in breast cancer patients.

[PURPOSE] Trastuzumab, the first anti-human epidermal growth factor receptor 2 (HER2)-targeted drug, is limited by adverse drug events (ADEs). The next-generation antibody-drug conjugates trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) exhibit enhanced efficacy and safety profiles compared with trastuzumab. In this study, we utilized US Food and Drug Administration Adverse Event Reporting System (FAERS) data to compare the ADEs of all three drugs, to facilitate personalized clinical decision-making and targeted monitoring.

[METHODS] ADE reports for patients with breast cancer using trastuzumab, T-DXd, or T-DM1 were retrieved. ADEs were classified using preferred terms (PT), standardized MedDRA queries (SMQs), and system organ classes (SOCs). Data mining using reported odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-Poisson shrinker was conducted.

[RESULTS] Overall, 20,829 cases of trastuzumab, 4565 cases of T-DXd, and 2975 cases of T-DM1 were included. With regard to SMQ terms, trastuzumab had a higher signal intensity for cardiac toxicity, and the RORs for "cardiomyopathy" of trastuzumab, T-DXd and T-DM1 were 8.59, 1.33, and 1.84, respectively. Meanwhile, T-DXd showed stronger signals for lung toxicity and T-DM1 showed prominent hepatotoxicity signals. Based on the differences between trastuzumab, T-DXd and T-DM1, this study established an individualized medication selection flowchart.

[CONCLUSIONS] This study applied four algorithms to analyze and compare ADEs associated with trastuzumab, T-DXd, or T-DM1. By integrating multi-level analysis including PT, SMQ, and SOC, this study provides a comprehensive safety perspective to guide clinical decision-making and medication monitoring for patients with breast cancer receiving HER2-targeted therapy.