Disproportionality analysis of hematologic adverse events associated with trastuzumab deruxtecan using the Japanese pharmacovigilance database.

PURPOSE: To evaluate the disproportionality, time to onset, reporting frequency, and outcomes of hematologic AEs associated with trastuzumab deruxtecan (T-DXd) using data from the Japanese Adverse Drug Event Report database (JADER).

METHODS

We analyzed data for the period from April 2004 to December 2024. Data on hematologic AEs were extracted, and the disproportionality of T-DXd-associated AEs was assessed by calculating reporting odds ratios.

RESULTS

Among the 3,221,393 reports analyzed, 1561 were associated with T-DXd, including 433 hematologic AEs. Signals were detected for six AEs, including febrile neutropenia, anaemia, neutrophil count decreased, neutropenia, platelet count decreased, and myelosuppression. All had fatal cases, with particularly high fatality rates observed for febrile neutropenia and platelet count decreased. A histogram of median times to onset showed that febrile neutropenia and platelet count decreased typically occurred within 8 to 10.5 days after administration. Weibull distribution analysis indicated that febrile neutropenia showed an early-onset tendency (early failure type), whereas platelet count decreased occurred in a dose-dependent manner (wear-out failure type).

CONCLUSIONS

Some hematologic AEs associated with T-DXd can be fatal and may occur not only early in treatment but also later in the course. Continuous monitoring is essential for their timely detection and appropriate management.