背景和目的:萨妥珠单抗戈维替康(SG),第一个针对人滋养层细胞表面抗原2(Trop-2)的抗体-药物缀合物,已被美国食品药品监督管理局(FDA)批准用于治疗晚期或转移性乳腺癌和尿路上皮癌。然而,目前,在大样本队列中,有关SG安全性的信息缺乏.本研究的目的是利用FDA不良事件报告系统(FAERS)数据库在现实世界中调查SG相关不良事件(AE),以指导临床用药的安全管理。方法:回顾性查询FAERS数据库,以提取2020年4月至2023年3月与SG相关的报告。为了识别和评估接受SG的患者的潜在不良事件,各种不相称性分析,如报告优势比(ROR),比例报告比率(PRR),贝叶斯置信度传播神经网络(BCPNN),并采用了多项目伽玛泊松收缩器(MGPS)。结果:总体而言,确定了2069份SG为“主要嫌疑人”的报告。值得注意的是,SG与血液淋巴系统疾病的风险增加显著相关(ROR,7.18;95%CI,6.58-7.84)和肝胆疾病(ROR,2.68;95%CI,2.17-3.30)在系统器官类(SOC)水平。同时,61个显著不成比例偏好项(PT)同时符合所有四种算法。其中,贫血,血小板减少症,中性粒细胞减少症,白细胞减少症,腹泻,虚弱,脱发,和电解质失衡与SG临床试验和规范中描述的常见不良事件一致。此外,意外的显著AE包括结肠炎(ROR,12.09;95%CI,9.1-16.08),心率增加(ROR,5.11;95%CI,3.84-6.79),脓毒症(ROR,4.77;95%CI,3.59-6.34),胆汁淤积(ROR,6.28;95%CI,3.48-11.36),血胆红素升高(ROR,4.65;95%CI,2.42-8.94)和脑膜炎(ROR,7.23;95%CI,2.71-19.29)也被检测到。SG相关AE的中位发病时间为14[四分位距(IQR),7-52天,大多数发生在SG治疗的最初一个月内。结论:我们的研究验证了常见的AE,并且还发现了一些与实际临床实践中SG相关的潜在出现的安全问题。这可以为临床医生和药剂师管理SG的安全问题提供有价值的警惕证据。
Background and objective: Sacituzumab govitecan (SG), the first antibody-drug conjugate targeting human trophoblast cell-surface antigen 2 (Trop-2), has been approved by the Food and Drug Administration (FDA) for the treatment of advanced or metastatic breast cancer and urothelial cancer. However, there is currently a dearth of information regarding the safety profiles of SG in a large sample cohort. The objective of the present
study is to investigate SG-related adverse events (AEs) in real-world settings leveraging the FDA Adverse Event Reporting System (FAERS) database to guide the safety management of clinical medication. Methods: The FAERS database was retrospectively queried to extract reports associated with SG from April 2020 to March 2023. To identify and evaluate potential AEs in patients receiving SG, various disproportionality analyses such as reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed. Results: Overall, 2069 reports of SG as the \"primary suspect\" were identified. Noteworthy, SG was significantly associated with an increased risk of blood lymphatic system disorders (ROR, 7.18; 95% CI, 6.58-7.84) and hepatobiliary disorders (ROR, 2.68; 95% CI, 2.17-3.30) at the System Organ Class (SOC) level. Meanwhile, 61 significant disproportionality preferred terms (PTs) simultaneously complied with all four algorithms were adopted. Therein, anemia, thrombocytopenia, neutropenia, leukopenia, diarrhea, asthenia, alopecia, and electrolyte imbalance were consistent with the common AEs described in the clinical trials and specification of SG. Furthermore, unexpected significant AEs include colitis (ROR, 12.09; 95% CI, 9.1-16.08), heart rate increased (ROR, 5.11; 95% CI, 3.84-6.79), sepsis (ROR, 4.77; 95% CI, 3.59-6.34), cholestasis (ROR, 6.28; 95% CI, 3.48-11.36), blood bilirubin increased (ROR, 4.65; 95% CI, 2.42-8.94) and meningitis (ROR, 7.23; 95% CI, 2.71-19.29) were also be detected. The median time to onset of SG-related AEs was 14 [interquartile range (IQR), 7-52] days, with the majority occurring within the initial month of SG treatment. Conclusion: Our
study validates the commonly known AEs and also found some potentially emerging safety issues related to SG in real-world clinical practice, which could provide valuable vigilance evidence for clinicians and pharmacists to manage the safety issues of SG.