OpenLB
Open Library of Bioscience
Advanced Search
Current medical science
Mar 25, 2025;

Toxicities Associated with Sacituzumab Govitecan: Data from Clinical Trials and a Real-World Pharmacovigilance Database.

Qiao-Yun Tan, Xiang-Ping Mei, Yue Hu, Hong-Ge Wu, Lin-Ka Xie, Jie Xiong, Jing Yao
Author Information
  1. Qiao-Yun Tan: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  2. Xiang-Ping Mei: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  3. Yue Hu: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  4. Hong-Ge Wu: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  5. Lin-Ka Xie: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  6. Jie Xiong: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  7. Jing Yao: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 2007XH0839@hust.edu.cn. ORCID
PMID: 40131630 DOI: 10.1007/s11596-025-00030-6

Abstract

OBJECTIVE: This study aimed to analyze the adverse effects (AEs) of sacituzumab govitecan (SG) through multiple sources of data to provide a reference for clinical safety management.
METHODS: Clinical trials of SG with available safety data were retrieved and included in the pooled analysis. The adverse drug reaction (ADR) signals of SG were collected from the FDA Adverse Event Reporting System (FAERS) database. Drug interactions with SG in the DDInter database were summarized.
RESULTS: A total of 6 clinical trials involving 1737 patients were included in the pooled analysis, and the most common AEs of ≥ grade 3 were neutropenia (46%), leukopenia (13%), and anemia (8%). In the pharmacovigilance study, 1024 AE reports were extracted, and the most common toxicities of SG were hematologic and gastrointestinal. AEs not included in the drug instructions also presented high signals, such as meningitis, colitis and lymphedema. A total of 40 drugs identified could induce drug-drug interactions when they were concomitantly administered with SG.
CONCLUSIONS: This study provides the most comprehensive profile of SG toxicity on the basis of data from clinical trials and the FRAES and DDInter databases. Attention should be given not only to common ADRs but also to ADRs not reported in drug instructions, and potential drugs that can induce drug-drug interactions.

Keywords

Clinical trial Pharmacovigilance Sacituzumab govitecan Toxicity

References

  1. Tarantino P, Carmagnani Pestana R, Corti C, et al. Antibody-drug conjugates: Smart chemotherapy delivery across tumor histologies. CA Cancer J Clin. 2022;72(2):165–182. [PMID: 34767258]
  2. Jin Y, Schladetsch MA, Huang X, et al. Stepping Forward in Antibody-drug Conjugate Development. Pharmacol Ther. 2022;229:107917. [PMID: 34171334]
  3. Sheikh MS, Huang Y. Antibody-drug Conjugates for Breast Cancer Treatment.Recent Pat Anti-Canc. 2023;18(2):108–113.
  4. Criscitiello C, Morganti S, Curigliano G. Antibody-drug conjugates in solid tumors: a look into novel targets. J Hematol Oncol. 2021;14(1):20. [PMID: 33509252]
  5. Cubas R, Zhang S, Li M, et al. Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Mol Cancer. 2010;9:253 [PMID: 20858281]
  6. Goldenberg DM, Sharkey RM. Sacituzumab govitecan, a novel, third-generation, antibody-drug conjugate (ADC) for cancer therapy. Expert Opin Biol Th. 2020;20(8):871–885.
  7. Wahby S, Fashoyin-Aje L, Osgood CL, et al. FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. Clin Cancer Res. 2021;27(7):1850–1854. [PMID: 33168656]
  8. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021;384(16):1529–1541. [PMID: 33882206]
  9. Loriot Y, Petrylak DP, Rezazadeh Kalebasty A, 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: updated safety and efficacy outcomes. Ann Oncol. 2024;35(4):392–401. [PMID: 38244927]
  10. Rugo HS, Bardia A, Marmé F, et al. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer. J Clin Oncol. 2022;40(29):3365–3376. [PMID: 36027558]
  11. Heist RS, Guarino MJ, Masters G, et al. Therapy of Advanced Non-Small-Cell Lung Cancer With an SN-38-Anti-Trop-2 Drug Conjugate, Sacituzumab Govitecan. J Clin Oncol. 2017;35(24):2790–2797. [PMID: 28548889]
  12. Gray JE, Heist RS, Starodub AN, et al. Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I–inhibiting Antibody–Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Clin Cancer Res. 2017;23(19):5711–5719. [PMID: 28679770]
  13. Mahalingaiah PK, Ciurlionis R, Durbin KR, et al. Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates. Pharmacol Therapeut. 2019;200:110–125.
  14. Murad MH, Asi N, Alsawas M, et al. New evidence pyramid. Evid Based Med. 2016;21(4):125–127. [PMID: 27339128]
  15. Ventola CL. Big Data and Pharmacovigilance: Data Mining for Adverse Drug Events and Interactions. Pharmacol Ther. 2018;43(6):340–351.
  16. Burgess S, Butterworth A, Thompson SG. Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data. Genet Epidemiol. 2013;37(7):658–665. [PMID: 24114802]
  17. Böhm R, Höcker J, Cascorbi I, et al. OpenVigil—free eyeballs on AERS pharmacovigilance data. Nat Biotechnol. 2012;30(2):137–138. [PMID: 22318027]
  18. Raschi E, Girardi A, Poluzzi E, et al. Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative Analysis of FAERS and CAERS Reporting Systems. Drug Saf. 2018;41(8):745–752. [PMID: 29582393]
  19. Salem JE, Manouchehri A, Moey M, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018;19(12):1579–1589. [PMID: 30442497]
  20. Xiong G, Yang Z, Yi J, et al. DDInter: an online drug-drug interaction database towards improving clinical decision-making and patient safety. Nucleic Acids Res. 2022;50(D1):D1200–D1207. [PMID: 34634800]
  21. Professional Committee on Clinical Research of Oncology Drugs, Chinese Anti-Cancer Association, Expert Committee for Monitoring the Clinical Application of Antitumor Drugs, Breast Cancer Expert Committee of National Cancer Quality Control Center, Cancer Chemotherapy Quality Control Expert Committee of Beijing Cancer Treatment Quality Control and Improvement Center. Expert consensus on the clinical application of antibody drug conjugates in the treatment of malignant tumors (2023 edition). Zhonghua Zhong Liu Za Zhi (Chinese). 2023;45(9):741–762.
  22. Liu F, Ke J, Song Y. T-DM1-induced thrombocytopenia in breast cancer patients: New perspectives. Biomed Pharmacother. 2020;129:110407. [PMID: 32570117]
  23. Kuter DJ. Treatment of chemotherapy-induced thrombocytopenia in patients with non-hematologic malignancies. Haematol J. 2022;107(6):1243–1263.
  24. Syed YY. Sacituzumab Govitecan: First Approval. Drugs. 2020;80(10):1019–1025. [PMID: 32529410]
  25. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2014;370(11):997–1007. [PMID: 24450857]
  26. Lüftner D, Fasching PA, Haidinger R, et al. ABC6 Consensus: Assessment by a Group of German Experts. Breast Care (Basel). 2022;17(1):90–100. [PMID: 35355695]
  27. Bergqvist V, Hertervig E, Gedeon P, et al. Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis. Cancer Immunol Immunother. 2017;66(5):581–592. [PMID: 28204866]
  28. Shivaji UN, Jeffery L, Gui X, et al. Immune checkpoint inhibitor-associated gastrointestinal and hepatic adverse events and their management. Therap Adv Gastroenterol. 2019;12:1756284819884196. [PMID: 31723355]
  29. Shah MH, Lorigan P, O’Brien MER, et al. Phase I study of IMGN901, a CD56-targeting antibody-drug conjugate, in patients with CD56-positive solid tumors. Invest New Drugs. 2016;34:290–299. [PMID: 26961907]
  30. McLaughlin SA, Staley AC, Vicini F, et al. Considerations for Clinicians in the Diagnosis, Prevention, and Treatment of Breast Cancer-Related Lymphedema: Recommendations from a Multidisciplinary Expert ASBrS Panel. Ann Surg Oncol. 2017;24(10):2818–2826. [PMID: 28766232]
  31. Rockson SG. Lymphedema after Breast Cancer Treatment. N Engl J Med. 2018;379(20):1937–1944. [PMID: 30428297]
  32. Krop IE, Suter TM, Dang CT, et al. Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo)Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early-Stage Breast Cancer. J Clin Oncol. 2015;33(10):1136–1142. [PMID: 25713436]
  33. Procter M, Suter TM, de Azambuja E, et al. Longer-Term Assessment of Trastuzumab-Related Cardiac Adverse Events in the Herceptin Adjuvant (HERA) Trial. J Clin Oncol. 2010;28(21):3422–3428. [PMID: 20530280]
  34. Lenihan D, Suter T, Brammer M, et al. Corrections to “Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab.” Ann Oncol. 2019;30(6):1021. [PMID: 30624607]
  35. Yin Q, Wu L, Han L, et al. Immune-related adverse events of immune checkpoint inhibitors: a review. Front Immunol. 2023;14:1167975. [PMID: 37304306]
  36. Shen K, Ma X, Zhu C, et al. Safety and Efficacy of Trastuzumab Emtansine in Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: a Meta-analysis. Sci Rep. 2016;6:23262. [PMID: 26979925]
  37. Dowling GP, Daly GR, Keelan S, et al. Efficacy and Safety of Trastuzumab Deruxtecan in Breast Cancer: A Systematic Review and Meta-Analysis. Clin Breast Cancer. 2023;23(8):847–855. [PMID: 37775347]
  38. O’Donnell PH, Milowsky MI, Petrylak DP, et al. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2023;41(25):4107–4117. [PMID: 37369081]
  39. Zschäbitz S, Biernath N, Hilser T, et al. Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort. Eur Urol Open Sci. 2023;53:31–37. [PMID: 37441344]
  40. Bardia A, Messersmith WA, Kio EA, et al. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Ann Oncol. 2021;32(6):746–756.
  41. Yap TA, Hamilton E, Bauer T, et al. Phase Ib SEASTAR Study: Combining Rucaparib and Sacituzumab Govitecan in Patients With Cancer With or Without Mutations in Homologous Recombination Repair Genes. JCO Precis Oncol. 2022;6:e2100456.
  42. Marmé F, Hanusch C, Furlanetto J, et al. 58O Safety interim analysis (SIA) of the phase III postneoadjuvant SASCIA study evaluating sacituzumab govitecan (SG) in patients with primary HER2-negative breast cancer (BC) at high relapse risk after neoadjuvant treatment. Ann Oncol. 2022;33:S148–S149.
Journal Article

Word Cloud

Created with Highcharts 10.0.0SGstudyAEsdataclinicalClinicaltrialsincludeddruginteractionscommonadversegovitecansafetypooledanalysissignalsdatabaseDDIntertotalinstructionsalsodrugsinducedrug-drugADRsSacituzumabPharmacovigilanceOBJECTIVE:aimedanalyzeeffectssacituzumabmultiplesourcesprovidereferencemanagementMETHODS:availableretrievedreactionADRcollectedFDAAdverseEventReportingSystemFAERSDrugsummarizedRESULTS:6involving1737patientsof ≥ grade3neutropenia46%leukopenia13%anemia8%pharmacovigilance1024AEreportsextractedtoxicitieshematologicgastrointestinalpresentedhighmeningitiscolitislymphedema40identifiedconcomitantlyadministeredCONCLUSIONS:providescomprehensiveprofiletoxicitybasisFRAESdatabasesAttentiongivenreportedpotentialcanToxicitiesAssociatedGovitecan:DataTrialsReal-WorldDatabasetrialToxicity

Similar Articles

Cited By