Objective  To mine and analyze the adverse drug event (ADE) signals of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) using the Japanese Adverse Drug Event Reporting (JADER) database, and to provide reference for safe clinical use of the two drugs in Asian populations.

Methods  The ADEs reported for T-DM1 and T-DXd from the Japanese JADER database from January 2014 to June 2024 were mined and analyzed using the reporting odds ratio method, Medicines and Healthcare products Regulatory Agency method, and information component method.

Results  A total of 1 013 ADE reports were extracted for T-DM1, involving 733 patients. 38 ADE signals were detected, and 18 ADE signals were not documented in package inserts in China. Similarly, 1 224 ADE reports were obtained for T-DXd, involving 732 patients. A total of 25 ADE signals were detected, and 10 ADE signals not documented in package inserts in China. The ADE signals of T-DM1 were involved in the system organ class (SOC) with unique conditions such as cardiac disorders, nervous system disorders, and ocular organ diseases. The ADE signals of T-DXd were involved in the SOC with unique conditions such as infections and infestations, general disorders and administration site conditions.

Conclusion  T-DM1 and T-DXd exhibit differences in terms of high-frequency ADE, SOC distribution, and overall safety profiles. In clinical practice, it is important to enhance our understanding of the primary ADEs and differential ADEs associated with T-DM1 and T-DXd. Additionally, close monitoring of patients' parameters, including blood routine, pulmonary function, hepatic function, and cardiac function, should be carried out throughout the treatment period to enable timely intervention when necessary.

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