Post-marketing safety surveillance of ado-trastuzumab emtansine: a real-world data retrospective cohort study using disproportionality analysis.

Abstract

Background: Ado-trastuzumab emtansine (T-DM1) is prescribed for HER2-positive, metastatic breast cancer or early breast cancer after neoadjuvant therapy. Although several adverse events (AEs) have been reported, there remains a need for a comprehensive evaluation of its safety profile.

Research design and methods: To quantify the signals of ado-trastuzumab emtansine associated AEs, we employed the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms.

Results: Between Q1 2013 and Q4 2022, 3699 patient reports of AEs associated with ado-trastuzumab emtansine were received, including 440 cases of ado-trastuzumab emtansine-induced bleeding events. Of the 3699 patient reports, 142 significant disproportionality preferred terms (PTs) were identified. New AEs have been identified with ado-trastuzumab emtansine administration, including telangiectasia, spider nevus, pericardial effusion, pleural effusion, radiation necrosis, and corneal disorders. The most common bleeding events were observed in the digestive system (27.05%), respiratory system (35.00%), and nervous system (14.55%). Hemorrhagic adverse events exhibited early failure-type characteristics.

Conclusion: This analysis offers the most comprehensive overview of ado-trastuzumab emtansine induced hemorrhage to date, shedding new light on this severe complication. Understanding the underlying mechanisms of these positive PTs can provide useful insights for further research.