Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study.

Abstract

This study aimed to explore the safety profile of trastuzumab deruxtecan (T-DXd, formerly DS-8201a) using multi-source medical data. We explored trastuzumab deruxtecan related adverse events (AEs) in clinical trials available in ClinicalTrials.gov and electronic databases (MEDLINE, EMBASE and PubMed) up to July 16, 2022. Meta-analysis was performed by using incidence rate with 95%CIs. In the pharmacovigilance study of FDA Adverse Event Reporting System (FAERS), the reporting odds ratio (ROR) and the medicines and healthcare products regulatory agency (MHRA) methods were used to analyse the real-world AEs (up to June 28, 2022). A 8 clinical trials enrolled 1457 patients were included. The most common AEs of any grade were gastrointestinal disorders and blood and lymphatic system disorders. The most common AE of grade 3 or higher was neutropenia (21.4%, 95%CI: 14.7%-28.1%, I2 = 91%). The incidence of interstitial lung disease (ILD) and decreased left ventricular ejection fraction were 10.9% (95%CI: 7.2%-14.5%, I2 = 82%) and 1.2% (95%CI: 0.7%-2.2%, I2 = 98%), respectively. A total of 1244 AE reports were identified in the pharmacovigilance study. Gastrointestinal toxicity (ROR=21.65), myelosuppression (ROR=36.88), interstitial lung disease (ROR=50.30), pneumonitis (ROR=36.59), decreased ejection fraction (ROR=16.08), and taste disorder (ROR=14.06) mentioned in the instructions showed strong signals. Also, ascites (ROR=14.90), lung opacity (ROR=78.80), pulmonary fibrosis (ROR=5.59), and increased KL-6 (ROR=1761.97), which were not mentioned in the instructions, showed strong signals. Trastuzumab deruxtecan was well tolerated, and more attention should be paid on ILD as well as decreased ejection fraction.