Sign Up Submit Enquiry

A meta-analysis and systematic review of the first Trop-2-targeting antibody–drug conjugate (sacituzumab govitecan) in treating metastatic breast cancer

Home A meta-analysis and systematic review of the first Trop-2-targeting antibody–drug conjugate (sacituzumab govitecan) in treating metastatic breast cancer

Related Articles

Contact us

Article Content

Abstract

Objectives

To assess the effectiveness and safety of sacituzumab govitecan in metastatic breast cancer (MBC), we performed a meta-analysis of randomized controlled trials comparing sacituzumab govitecan with chemotherapy.

Methods

We systematically searched multiple databases for relevant studies. Primary outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events (AEs). Data were analyzed using RevMan 5.3 software.

Results

Three studies were included after rigorous screening and quality assessment. Compared with chemotherapy, sacituzumab govitecan significantly prolonged PFS [HR 0.57; 95% CI 0.43, 0.77; P = 0.0002], improved OS [HR 0.64; 95% CI 0.48, 0.85; P = 0.002], and increased ORR [RR 2.84; 95% CI 1.27, 6.37; P = 0.01]. However, sacituzumab govitecan was associated with higher incidence of AEs (P < 0.00001).

Conclusion

In this study, sacituzumab govitecan demonstrated improved PFS and OS compared to chemotherapy regimens in patients with MBC. Further research is required to validate its broad applicability and long-term treatment stability.

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

  • Cancer Immunotherapy
  • Cancer therapeutic resistance
  • Chemotherapy
  • CNS cancer
  • Molecularly targeted therapy
  • Targeted therapies

Data Availability

No datasets were generated or analysed during the current study.

References

  1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3):229–263

    Article PubMed Google Scholar

  2. Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147(2):275–292

    Article PubMed PubMed Central CAS Google Scholar

  3. Cao H, Zhang Z, Zhao S, He X, Yu H, Yin Q, Zhang Z, Gu W, Chen L, Li Y (2015) Hydrophobic interaction mediating self-assembled nanoparticles of succinobucol suppress lung metastasis of breast cancer by inhibition of VCAM-1 expression. Journal of controlled release : official journal of the Controlled Release Society 205:162–171

    Article PubMed CAS Google Scholar

  4. Sundquist M, Brudin L, Tejler G (2017) Improved survival in metastatic breast cancer 1985–2016. Breast (Edinburgh, Scotland) 31:46–50

    Article PubMed Google Scholar

  5. Hsu JY, Chang CJ, Cheng JS (2022) Survival, treatment regimens and medical costs of women newly diagnosed with metastatic triple-negative breast cancer. Sci Rep 12(1):729

    Article PubMed PubMed Central CAS Google Scholar

  6. Kohler BA, Sherman RL, Howlader N, Jemal A, Ryerson AB, Henry KA, Boscoe FP, Cronin KA, Lake A, Noone AM et al (2015) Annual report to the nation on the status of cancer, 1975–2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst 107(6):djv048

    Article PubMed PubMed Central Google Scholar

  7. Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA, Cronin KA (2014) US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst 106(5):dju055

  8. Aurilio G, Disalvatore D, Pruneri G, Bagnardi V, Viale G, Curigliano G, Adamoli L, Munzone E, Sciandivasci A, De Vita F et al: A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. European journal of cancer (Oxford, England : 1990) 2014, 50(2):277–289.

    Article CAS Google Scholar

  9. Lindström LS, Karlsson E, Wilking UM, Johansson U, Hartman J, Lidbrink EK, Hatschek T, Skoog L, Bergh J (2012) Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 30(21):2601–2608

    Article PubMed Google Scholar

  10. Park IH, Im SA, Jung KH, Sohn JH, Park YH, Lee KS, Sim SH, Park KH, Kim JH, Nam BH et al (2019) Randomized open label phase III trial of irinotecan plus capecitabine versus capecitabine monotherapy in patients with metastatic breast cancer previously treated with anthracycline and taxane: PROCEED trial (KCSG BR 11–01). Cancer Res Treat 51(1):43–52

    Article PubMed CAS Google Scholar

  11. Perez EA, Patel T, Moreno-Aspitia A (2010) Efficacy of ixabepilone in ER/PR/HER2-negative (triple-negative) breast cancer. Breast Cancer Res Treat 121(2):261–271

    Article PubMed CAS Google Scholar

  12. Pivot X, Marmé F, Koenigsberg R, Guo M, Berrak E, Wolfer A (2016) Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy. Ann Oncol 27(8):1525–1531

    Article PubMed PubMed Central CAS Google Scholar

  13. Li CH, Karantza V, Aktan G, Lala M (2019) Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review. Breast Cancer Res BCR 21(1):143

    Article PubMed Google Scholar

  14. Sharkey RM, McBride WJ, Cardillo TM, Govindan SV, Wang Y, Rossi EA, Chang CH, Goldenberg DM (2015) Enhanced delivery of SN-38 to human tumor xenografts with an anti-Trop-2-SN-38 antibody conjugate (sacituzumab govitecan). Clin Cancer Res 21(22):5131–5138

    Article PubMed CAS Google Scholar

  15. Goldenberg DM, Stein R, Sharkey RM (2018) The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget 9(48):28989–29006

    Article PubMed PubMed Central Google Scholar

  16. Ambrogi F, Fornili M, Boracchi P, Trerotola M, Relli V, Simeone P, La Sorda R, Lattanzio R, Querzoli P, Pedriali M et al (2014) Trop-2 is a determinant of breast cancer survival. PLoS ONE 9(5):e96993

    Article PubMed PubMed Central Google Scholar

  17. Vidula N, Yau C, Rugo H (2022) Trophoblast Cell Surface Antigen 2 gene (TACSTD2) expression in primary breast cancer. Breast Cancer Res Treat 194(3):569–575

    Article PubMed CAS Google Scholar

  18. Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O’Shaughnessy J, Moroose RL, Santin AD, Abramson VG et al (2019) Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med 380(8):741–751

    Article PubMed CAS Google Scholar

  19. Matusz-Fisher A, Tan AR (2022) Sacituzumab govitecan and other antibody-drug conjugates targeting trophoblast cell-surface antigen 2 (Trop-2) in breast cancer. Ann Transl Med 10(18):1031

    Article PubMed PubMed Central CAS Google Scholar

  20. Lopez S, Perrone E, Bellone S, Bonazzoli E, Zeybek B, Han C, Tymon-Rosario J, Altwerger G, Menderes G, Bianchi A et al (2020) Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. Oncotarget 11(5):560–570

    Article PubMed PubMed Central Google Scholar

  21. Goldenberg DM, Sharkey RM (2020) Sacituzumab govitecan, a novel, third-generation, antibody-drug conjugate (ADC) for cancer therapy. Expert Opin Biol Ther 20(8):871–885

    Article PubMed CAS Google Scholar

  22. Govindan SV, Cardillo TM, Sharkey RM, Tat F, Gold DV, Goldenberg DM (2013) Milatuzumab-SN-38 conjugates for the treatment of CD74+ cancers. Mol Cancer Ther 12(6):968–978

    Article PubMed CAS Google Scholar

  23. Kopp A, Hofsess S, Cardillo TM, Govindan SV, Donnell J, Thurber GM (2023) Antibody-drug conjugate sacituzumab govitecan drives efficient tissue penetration and rapid intracellular drug release. Mol Cancer Ther 22(1):102–111

    Article PubMed CAS Google Scholar

  24. Shvartsur A, Bonavida B (2015) Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Genes Cancer 6(3–4):84–105

    PubMed PubMed Central CAS Google Scholar

  25. Rugo HS, Bardia A, Marmé F, Cortés J, Schmid P, Loirat D, Trédan O, Ciruelos E, Dalenc F, Gómez Pardo P et al (2023) 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. Lancet (London, England) 402(10411):1423–1433

    Article PubMed CAS Google Scholar

  26. Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB et al (2021) Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med 384(16):1529–1541

    Article PubMed CAS Google Scholar

  27. O’Shaughnessy J, Brufsky A, Rugo HS, Tolaney SM, Punie K, Sardesai S, Hamilton E, Loirat D, Traina T, Leon-Ferre R et al (2022) Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer. Breast Cancer Res Treat 195(2):127–139

    Article PubMed PubMed Central Google Scholar

  28. Xu B, Wang S, Yan M, Sohn J, Li W, Tang J, Wang X, Wang Y, Im SA, Jiang D et al (2024) Sacituzumab govitecan in HR(+)HER2(-) metastatic breast cancer: the randomized phase 3 EVER-132-002 trial. Nat Med 30(12):3709–3716

    Article PubMed PubMed Central CAS Google Scholar

  29. Loibl S, Gianni L (2017) HER2-positive breast cancer. Lancet (London, England) 389(10087):2415–2429

    Article PubMed CAS Google Scholar

  30. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet (London, England) 376(9742):687–697

    Article PubMed CAS Google Scholar

  31. Nicolò E, Zagami P, Curigliano G (2020) Antibody-drug conjugates in breast cancer: the chemotherapy of the future? Curr Opin Oncol 32(5):494–502

    Article PubMed Google Scholar

  32. Barok M, Joensuu H, Isola J (2014) Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res 16(2):209

    Article PubMed PubMed Central Google Scholar

  33. Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF et al (2022) Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med 386(12):1143–1154

    Article PubMed Google Scholar

  34. Cortés J, Hurvitz SA, Im SA, Iwata H, Curigliano G, Kim SB, Chiu JWY, Pedrini JL, Li W, Yonemori K et al (2024) Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial. Nat Med 30(8):2208–2215

    Article PubMed PubMed Central Google Scholar

  35. Cubas R, Li M, Chen C, Yao Q (2009) Trop2: a possible therapeutic target for late stage epithelial carcinomas. Biochem Biophys Acta 1796(2):309–314

    PubMed CAS Google Scholar

  36. Trerotola M, Cantanelli P, Guerra E, Tripaldi R, Aloisi AL, Bonasera V, Lattanzio R, de Lange R, Weidle UH, Piantelli M et al (2013) Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene 32(2):222–233

    Article PubMed CAS Google Scholar

  37. Stepan LP, Trueblood ES, Hale K, Babcook J, Borges L, Sutherland CL (2011) Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: potential implications as a cancer therapeutic target. J Histochem Cytochem 59(7):701–710

    Article PubMed PubMed Central CAS Google Scholar

  38. Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM (2011) Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res 17(10):3157–3169

    Article PubMed PubMed Central CAS Google Scholar

  39. Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM (2015) Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget 6(26):22496–22512

    Article PubMed PubMed Central Google Scholar

  40. Zaman S, Jadid H, Denson AC, Gray JE (2019) Targeting Trop-2 in solid tumors: future prospects. Onco Targets Ther 12:1781–1790

    Article PubMed PubMed Central CAS Google Scholar

  41. Jabbarzadeh Kaboli P, Shabani S, Sharma S, Partovi Nasr M, Yamaguchi H, Hung MC (2022) Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates. Am J Cancer Res 12(4):1671–1685

    PubMed PubMed Central Google Scholar

  42. Sheikh MS, Huang Y (2022) Antibody-drug conjugates for breast cancer treatment. Recent Pat Anticancer Drug Discov 18(2):108–113

    Article PubMed Google Scholar

  43. Rugo HS, Tolaney SM, Loirat D, Punie K, Bardia A, Hurvitz SA, O’Shaughnessy J, Cortés J, Diéras V, Carey LA et al (2022) Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer 8(1):98

    Article PubMed PubMed Central CAS Google Scholar

  44. Bardia A, Jhaveri K, Im SA, Pernas S, De Laurentiis M, Wang S, Martínez Jañez N, Borges G, Cescon DW, Hattori M et al (2025) Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: primary results from TROPION-Breast01. J Clin Oncol 43(3):285–296

    Article PubMed CAS Google Scholar

Download references

Acknowledgements

Acknowledgments Figure 1 Made by figdraw.

Funding

(1) Natural Science Foundation of Zhejiang Province (LY24H270010)

(2) Zhejiang Lin Shengyou famous Traditional Chinese Medicine expert inheritance studio project (GZS202002).

Author information

Author notes

  1. Jue Wang, Shengyou Lin, and Jialin Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, 310007, China

    Jue Wang & Jialin Zhang

  2. Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, China

    Shengyou Lin

  3. Department of General Internal Medicine, Tongde HospitalAffiliated to, Zhejiang Chinese Medical University (Tongde Hospital of Zhejiang Province) , Hangzhou, 310012, China

    Jingyang Su

Contributions

Study design and manuscript drafting were done by Jue Wang and Shengyou Lin. Literature search and data collection were done by Shengyou Lin. Figures, table, and data analysis were done by Jue Wang, Jialin Zhang. Manuscript revision and article polish were done by and Jingyang Su. Manuscript finalization and funds support were done by Jingyang Su. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jingyang Su.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 30.6 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Lin, S., Zhang, J. et al. A meta-analysis and systematic review of the first Trop-2-targeting antibody–drug conjugate (sacituzumab govitecan) in treating metastatic breast cancer. Eur J Clin Pharmacol (2025). https://doi.org/10.1007/s00228-025-03876-w

Download citation

  • Received
  • Accepted
  • Published
  • DOI https://doi.org/10.1007/s00228-025-03876-w

Keywords

  • Breast cancer
  • Sacituzumab govitecan
  • Antibody–drug conjugate
  • Trop-2
  • Adverse events

Copyright © All rights reserved Designed and Developed by Digital Flavers

WhatsApp