Signal mining and analysis of adverse events of sacituzumab govitecan

WANG Yilu; ZHANG Ke; LI Zhengxiang

doi:10.6039/j.issn.1001-0408.2024.20.15

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Signal mining and analysis of adverse events of sacituzumab govitecan

更新时间：2024-10-25

- Signal mining and analysis of adverse events of sacituzumab govitecan
- ZHONGGUO YAOFANG Vol. 35, Issue 20, Pages: 2527-2532(2024)
- 作者机构：
  
  天津医科大学总医院药剂科，天津　300052
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.20.15
  CLC： R969.3
- Published：30 October 2024，
  
  Received：10 June 2024，
  
  Revised：10 September 2024，
- 稿件说明：
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王艺璐,张科,李正翔.戈沙妥珠单抗的药物不良事件信号挖掘与分析 ^Δ[J].中国药房,2024,35(20):2527-2532.

WANG Yilu,ZHANG Ke,LI Zhengxiang.Signal mining and analysis of adverse events of sacituzumab govitecan[J].ZHONGGUO YAOFANG,2024,35(20):2527-2532.
王艺璐,张科,李正翔.戈沙妥珠单抗的药物不良事件信号挖掘与分析 ^Δ[J].中国药房,2024,35(20):2527-2532. DOI： 10.6039/j.issn.1001-0408.2024.20.15.

WANG Yilu,ZHANG Ke,LI Zhengxiang.Signal mining and analysis of adverse events of sacituzumab govitecan[J].ZHONGGUO YAOFANG,2024,35(20):2527-2532. DOI： 10.6039/j.issn.1001-0408.2024.20.15.

摘要

目的

挖掘戈沙妥珠单抗的药物不良事件（ADE）信号，为其临床安全用药提供参考。

方法

收集美国FDA不良事件报告系统（FAERS）2020年4月1日至2024年4月30日上报的戈沙妥珠单抗ADE数据。采用报告比值比法、英国药品和保健品管理局综合标准法、贝叶斯置信度递进神经网络法进行数据挖掘。利用《国际医学用语词典》27.0版ADE术语集中的系统器官分类（SOC）、首选术语（PT）进行分类统计。

结果

共得到戈沙妥珠单抗ADE报告753份，包括46个ADE信号，涉及12个SOC、13个说明书中未记载的新的可疑的ADE信号。发生频次排名前5位的PT分别为疾病进展、死亡、腹泻、超说明书使用、产品给予时间表不当。信号强度排名前5位的PT分别为发热性骨髓再生障碍、中性粒细胞减少性结肠炎、疾病进展、肺脓毒症、一般身体状况异常。药品说明书未记录的新的可疑的ADE包括中性粒细胞减少性脓毒症、肝细胞溶解、脑膜炎、发育不全等。

结论

临床使用戈沙妥珠单抗时，应特别关注发热性中性粒细胞减少症、发热性骨髓再生障碍、体重波动、结肠炎等报告例数多且信号强度高的ADE；还应警惕中性粒细胞减少性脓毒症、肝细胞溶解、脑膜炎、发育不全等新的可疑的ADE，以保障患者用药安全。

Abstract

OBJECTIVE

To mine the adverse drug event （ADE） signals of sacituzumab govitecan and provide a reference for its clinical safety application.

METHODS

The data of sacituzumab govitecan-related ADE reports were collected from the FDA Adverse Event Reporting System （FAERS） database from April 1， 2020 to April 30， 2024. The reporting odds ratio（ROR） method， the United Kingdom Medicines and Healthcare Products Regulatory Agency comprehensive standard method （MHRA） and Bayesian confidence propagation neural network （BCPNN） method were used for data mining. Systematic organ classification （SOC） and preferred term （PT） in the ADE terminology set of version 27.0 of the

Medical Dictionary for Regulatory Activities

（MedDRA） were used for data classification and statistics.

RESULTS

A total of 753 ADE reports were obtained for sacituzumab govitecan， including 46 ADE signals， involving 12 SOCs， and 13 new suspicious ADE signals not recorded in the instructions. Top 5 PTs in terms of occurrence frequency were disease progression， death， diarrhea， off label use and inappropriate schedule of product administration. Top 5 PTs in terms of signal strength were febrile bone marrow aplasia， neutropenic colitis， disease progression， pulmonary sepsis， general physical condition abnormal. New ADE not recorded in the drug instructions included neutropenic sepsis， hepatic cytolysis， meningitis， aplasia， etc.

CONCLUSIONS

When using sacituzumab govitecan in clinical practice， special attention should be paid to ADE with highly reported cases and strong signal intensity， such as febrile neutropenia， febrile bone marrow aplasia， weight fluctuations， colitis. We should also be alert to new suspected ADE such as neutropenic sepsis， hepatic cytolysis， meningitis， and aplasia to ensure patient medication safety.

关键词

戈沙妥珠单抗药物不良事件抗体-药物偶联物数据挖掘

Keywords

adverse drug eventantibody-drug conjugatedata mining

references

张娣，黎立喜，马飞. 戈沙妥珠单抗在乳腺癌及其他实体瘤中临床应用的研究进展[J]. 癌症，2022，41（6）：253-258.

ZHANG D，LI L X，MA F. Research progress of clinical application of sacituzumab govitecan in breast cancer and other solid tumors[J]. Chin J Cancer，2022，41（6）：253-258.

LIANG Y，ZHANG P R，LI F，et al. Advances in the study of marketed antibody-drug conjugates（ADCs）for the treatment of breast cancer[J]. Front Pharmacol，2024，14：1332539.

WAHBY S，FASHOYIN-AJE L，OSGOOD C L，et al. FDA approval summary：accelerated approval of sacituzumab govitecan-hziy for third-line treatment of metastatic triple-negative breast cancer[J]. Clin Cancer Res，2021，27（7）：1850-1854.

Gilead. U.S.FDA grants accelerated approval to Trodelvy® for the treatment of metastatic urothelial cancer [EB/OL].（2021-04-13）[2024-07-09]. https：//www.gilead.com/news-and-press/press-room/press-releases/2021/4/us-fda-grants-accelerated-approval-to-trodelvy-for-the-treat-ment-of-metastatic-urothelial-cancerhttps://www.gilead.com/news-and-press/press-room/press-releases/2021/4/us-fda-grants-accelerated-approval-to-trodelvy-for-the-treat-ment-of-metastatic-urothelial-cancer.

吕铮，李响. 抗体偶联药物在乳腺癌治疗中的研究进展[J]. 中国肿瘤临床与康复，2023，30（7）：406-415.

LYU Z，LI X. Research progress of antibody-drug conjugate in the treatment of breast cancer[J]. Chin J Clin Oncol Rehabil，2023，30（7）：406-415.

RUGO H S，BARDIA A，MARMÉ F，et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer（TROPiCS-02）：a randomised，open-label，multicentre，phase 3 trial[J]. Lancet，2023，402（10411）：1423-1433.

HEIST R S，GUARINO M J，MASTERS G，et al. Therapy of advanced non-small-cell lung cancer with an SN-38-anti-Trop-2 drug conjugate，sacituzumab govitecan[J]. J Clin Oncol，2017，35（24）：2790-2797.

GRAY J E，HEIST R S，STARODUB A N，et al. Therapy of small cell lung cancer（SCLC）with a topoisomerase-Ⅰ-inhibiting antibody-drug conjugate（ADC）targeting Trop-2，sacituzumab govitecan[J]. Clin Cancer Res，2017，23（19）：5711-5719.

SANTIN A，KOMIYA T，GOLDENBERG D M，et al. Sacituzumab govitecan（SG）in patients（pts）with previously treated metastatic endometrial cancer（mEC）：results from a phase Ⅰ/Ⅱ study[J]. J Clin Oncol，2020，38（Suppl.15）：6081.

BARDIA A，HURVITZ S A，TOLANEY S M，et al. Sacituzumab govitecan in metastatic triple-negative breast cancer[J]. N Engl J Med，2021，384（16）：1529-1541.

龙霞，黄孟文，蒲诗云，等. 洛拉替尼的药物不良事件信号挖掘与分析[J]. 中国药房，2023，34（20）：2513-2518.

LONG X，HUANG M W，PU S Y，et al. Mining and analysis of lorlatinib-induced adverse drug event signals[J]. China Pharm，2023，34（20）：2513-2518.

周瑞珊，卢佩雯，陈君恒，等.药品不良反应数据挖掘技术在药物警戒中的应用[J]. 中国现代应用药学，2024，41（6）：864-870.

ZHOU R S，LU P W，CHEN J H，et al. Application of adverse drug reaction of data mining in pharmacovigilance[J].Chin J Mod Appl Pharm，2024，41（6）：864-870.

GOLDENBERG D M，STEIN R，SHARKEY R M. The emergence of trophoblast cell-surface antigen 2（Trop-2）as a novel cancer target[J]. Oncotarget，2018，9（48）：28989-29006.

TAGAWA S T，BALAR A V，PETRYLAK D P，et al. TROPHY-U-01：a phase Ⅱ open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors[J]. J Clin Oncol，2021，39（22）：2474-2485.

SRIVASTAVA A，AHMAD R，YADAV K，et al. An update on existing therapeutic options and status of novel anti-metastatic agents in breast cancer：elucidating the molecular mechanisms underlying the pleiotropic action of Withania somnifera（Indian ginseng）in breast cancer attenuation[J]. Int Immunopharmacol，2024，136：112232.

杨宏伟，陈茂山，李芳芳，等. 年龄与三阴性乳腺癌临床病理特征及预后的关系[J]. 中国普通外科杂志，2021，30（11）：1285-1293.

YANG H W，CHEN M S，LI F F，et al. Association of age at diagnosis with clinicopathologic features and prognosis in patients with triple-negative breast cancer[J]. Chin J Gen Surg，2021，30（11）：1285-1293.

FDA. TRODELVY®（sacituzumab govitecan-hziy）for injection，for intravenous use[EB/OL].（2023-02-03）[2024-07-09]. https：//www.accessdata.fda.gov/drugsatfda_docs/label/2023/761115s035lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761115s035lbl.pdf.

SHI M Q，LI Z J，WANG T Z，et al. Third-line treatment for metastatic triple-negative breast cancer：a systematic review and network meta-analysis[J]. Am J Clin Oncol，2024，47（2）：91-98.

AFZAL F，AIMAN W，ZAHOOR H，et al. Efficacy and safety of antibody-drug conjugates in triple-negative and HER-2 positive breast cancer：a systematic review and meta-analysis of clinical trials[J]. Breast Dis，2023，42（1）：121-136.

KATHPALIA M，SHARMA A，KAUR N. Sacituzumab govitecan as a second-line treatment in relapsed/refractory metastatic triple-negative breast cancer patients：a syste-matic review and meta-analysis[J]. Ann Pharmacother，2024，58（1）：44-53.

ETIENNE-GRIMALDI M C，BOYER J C，THOMAS F，et al. UGT1A1 genotype and irinotecan therapy：general review and implementation in routine practice[J]. Fundam Clin Pharmacol，2015，29（3）：219-237.

陈君瑶，张文涛，刘巧，等. 老年三阴性乳腺癌患者的临床困境和系统治疗策略[J]. 中国癌症杂志，2023，33（5）：506-516.

CHEN J Y，ZHANG W T，LIU Q，et al. Clinical dilemma and systemic treatment strategy of triple-negative breast cancer in the elderly[J]. China Oncol，2023，33（5）：506-516.

王浩，黄佳，钟薇，等.靶向Trop-2的抗体偶联药物：戈沙妥珠单抗[J].中国新药与临床杂志，2023，42（8）：498-502.

WANG H，HUANG J，ZHONG W，et al. Trop-2-targeted antibody-drug conjugate：sacituzumab govitecan [J]. Chin J New Drugs Clin Rem，2023，42（8）：498-502.

D’ARIENZO A，VERRAZZO A，PAGLIUCA M，et al. Toxicity profile of antibody-drug conjugates in breast cancer：practical considerations[J]. eClinicalMedicine，2023，62：102113.

LAMBERTINI M，PECCATORI FA，JrAZIM HA. Targeted agents for cancer treatment during pregnancy[J]. Cancer Treat Rev，2015，41（4）：301-309.

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