Toxicities associated with sacituzumab govitecan: Data from clinical trials and real-word pharmacovigilance database.

person Xiangping Mei Huazhong University of Science and Technology, Wuhan, China info_outline Xiangping Mei, Qiaoyun Tan, Jing Yao

Authors person Xiangping Mei Huazhong University of Science and Technology, Wuhan, China info_outline Xiangping Mei, Qiaoyun Tan, Jing Yao Organizations Huazhong University of Science and Technology, Wuhan, China Abstract Disclosures Research Funding Other Foundation New National Natural Science Foundation of China Background: This study aimed to analyze the adverse effect of sacituzumab govitecan (SG) with multiple source data, to provide reference for clinical medication safety management. Methods: Clinical trials of SG with available safety data were searched and included in the pooled analysis (up to January 5th, 2023). The adverse drug reaction (ADR) signals of SG were collected from the FDA Adverse Event Reporting System (FAERS) database up to January 1st, 2023. The ADR signals were presented and sorted by incidence frequency and reporting odds ratio (ROR) strength, respectively. We also searched and summarized drug interactions with SG in DDInter database. Results: A total of 6 clinical trials enrolled 1737 patients were included in pooled analysis, the most common adverse events of ≥3 grade were neutropenia (51.55%), leukopenia (14.50%), anemia (10.69%), diarrhea (7.30%), fatigue and asthenia (4.23%). In pharmacovigilance study, 1024 AE reports were extracted, the most common toxicities of SG are hematologic and gastrointestinal. AEs not included in the instructions also showed high signals, such as meningitis, colitis and lymphedema. A total of 40 drugs identified can induce drug-drug interaction when concomitant administration with SG. Conclusions: This study provides a comprehensive profile of SG based on clinical trial, FRAES and DDInter database, attention should be paid not only to the common ADRs, but also to the ADRs not reported in the drug instructions and potential drugs that induce drug-drug interactions. Top 10 adverse drug events associated with sacituzumab govitecan by ROR. PT SOC No. ROR(95%CI) PRR(x2) Bone marrow hypocellular Blood and lymphatic system disorders 28 149.46 (66.117-337.862) 147.764 (714.475) Sepsis Infections and infestations 15 73.747(36.515-148.942) 72.638(489.349) Gastrointestinal toxicity Gastrointestinal disorders 3 33.897(10.858-105.815) 33.709(64.916) meningitis a Infections and infestations 4 26.412(8.467-82.385) 26.266(49.601) Colitis a Gastrointestinal disorders 16 20.544(12.069-34.970) 20.023(233.800) Lymphedema a Vascular disorders 3 20.464(6.564-63.792) 20.352(37.415) Mucosal infection a Infections and infestations 7 17.677(8.375-37.309) 17.454(92.519) Febrile neutropenia Blood and lymphatic system disorders 20 16.352 (10.337-25.869) 15.797 (248.596) Neutropenia Blood and lymphatic system disorders 46 9.919 (7.037-13.980) 9.324 (253.220) Pneumonitis a Respiratory, thoracic and mediastinal disorders 6 9.759(4.042-23.565) 9.676(30.678) a Adverse drug events are not included in the label of sacituzumab govitecan c: This category includes the preferred terms fatigue, asthenia.