Adverse event profile differences between Trastuzumab Emtansine and Trastuzumab Deruxtecan: a real-world, pharmacovigilance study

Introduction: Trastuzumab emtansine(T-DM1) and trastuzumab deruxtecan (T-DXd, formerly DS-8201a), the human epidermal growth factor receptor 2 (HER-2)-targeted antibody-drug conjugate (ADC), are commonly used in metastatic breast cancer. However, their real-world safety profile has not been adequately compared. Objective We aimed to investigate the adverse event (AE) profile of T-DM1 and T-DXd reported by the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods All indications were searched for T-DM1 and T-DXd, as primary suspected drugs from FAERS data (December 2014 to December 2022). Disproportionality analyses were performed by reporting odds ratios (ROR). The AE with a total number of reports less than five or a lower limit of 95% confidence intervals (95% CI) of ROR less than one were excluded to avoid false positives༎ Results 6333 and 2032 reports of T-DM1 and T-DXd were submitted to FAERS. Finally, 171 and 42 significant signals for T-DM1 and T-DXd were systematically analyzed. The highest frequency and strongest signal of AE were neuropathy peripheral (4.90%) and hepatopulmonary syndrome (ROR = 487.34) for T-DM1, nausea (15.99%) and interstitial lung disease (ROR = 82.33) for T-DXd. Disproportionality analyses on the SOCs between T-DM1 and T-DXd were performed. T-DM1 occurred more frequently in cardiac disorders (ROR = 13.98), eye disorders (ROR = 3.88), hepatobiliary disorders (ROR = 1.42), infections and infestations (ROR = 1.32), investigations (ROR = 1.67), musculoskeletal and connective tissue disorders (ROR = 4.72), nervous system disorders (ROR = 4.61), skin and subcutaneous tissue disorders (ROR = 1.82), psychiatric disorders (ROR = 9.34) and vascular disorders (ROR = 6.38). While T-DXd occurred more frequently in blood and lymphatic system disorders, gastrointestinal disorders, administration site general condition disorders, metabolism and nutrition disorders, and respiratory, thoracic, and mediastinal disorders. Conclusions Significant differences in the AE profile between T-DM1 and T-DXd have been systematically described and analyzed, from which we recommend more attention should be paid to hematotoxicity, gastrointestinal toxicity, and ILD or pneumonia for T-DXd and thrombocytopenia, hepatobiliary disorder and peripheral neuropathy for T-DM1.