Disproportionality Analysis of Gastrointestinal Adverse Events Associated With Trastuzumab Deruxtecan Using the...

This study aimed to evaluate the disproportionality, times to onset, incidence rates, and outcomes of gastrointestinal adverse events (AEs) associated with trastuzumab deruxtecan (T-DXd), using data from the Japanese Adverse Drug Event Report database (JADER).

We analyzed data for the period from April 2004 to December 2024. Those on gastrointestinal AEs were extracted and the disproportionality of T-DXd-associated AEs was assessed by calculating reporting odds ratios (RORs).

Of the 3,221,393 reports analyzed, we identified 1,561 reports of AEs associated with T-DXd, including 264 gastrointestinal AEs. Signals were detected for seven gastrointestinal AEs: nausea, decreased appetite, vomiting, diarrhoea, ascites, dehydration, and enterocolitis. Fatal outcomes were reported for six of these events, excluding ascites, with particularly high fatality rates observed for diarrhoea, dehydration, and enterocolitis. A histogram of median times to onset indicated that gastrointestinal AEs associated with T-DXd occurred 3 to 84 days after administration. Weibull distributions showed that nausea, decreased appetite, and vomiting occurred constantly throughout the exposure period (random failure type), and diarrhoea and dehydration developed in a dose-dependent manner (wear-out failure-type).

Gastrointestinal adverse events associated with T-DXd can arise early or later in treatment and may lead to serious or fatal outcomes. These findings underscore the importance of continuous post-marketing surveillance and proactive clinical management to detect and mitigate these potentially severe AEs.