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Review paper
Published online: 2022-07-01
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Sacituzumab govitecan — a new therapy for patients with triple-negative breast cancer

Katarzyna Pogoda1, Agnieszka Jagiełło-Gruszfeld1, Anna Niwińska1, Zbigniew Nowecki1
DOI: 10.5603/OCP.2022.0003
Affiliations
  1. Department of Breast Cancer and Reconstructive Surgery, National Oncology Institute of Maria Sklodowska-Curie — National Research Institute, Warsaw

open access

Ahead of print
REVIEW ARTICLES
Published online: 2022-07-01

Abstract

Treatment outcomes in patients with metastatic triple-negative breast cancer (TNBC) have not improved significantly for many years. Modern treatments, including immune therapy and poly ADP-ribose polymerase (PARP) inhibitors, are available for a select group of TNBC patients. In many cases, classic chemotherapy remains the treatment of choice, which produces unsatisfactory response rates. The poor prognosis of patients with metastatic TNBC justifies intensive research on new drugs for this group of patients, including attempts to use conjugates. This article discusses the reports on sacituzumab govitecan (SG), which is composed of a monoclonal antibody targeting trophoblast-cell surface antigen 2 (Trop-2) expressed on many TNBC cells and linked to a payload (SN-38), the active metabolite of irinotecan. The structure and mechanism of action of this conjugate are presented. The available results of clinical trials with SG in breast cancer patients are summarized, including the results of the ASCENT registration study, which showed a significant improvement in the median progression-free survival, as well as overall survival, compared to classic chemotherapy in patients previously treated with advanced TNBC. The most common side effects of the drug are discussed, indicating principles of primary and secondary prophylaxis that allow for effective management of possible complications. Directions for further research in breast cancer patients on this very promising conjugate were also indicated.

Abstract

Treatment outcomes in patients with metastatic triple-negative breast cancer (TNBC) have not improved significantly for many years. Modern treatments, including immune therapy and poly ADP-ribose polymerase (PARP) inhibitors, are available for a select group of TNBC patients. In many cases, classic chemotherapy remains the treatment of choice, which produces unsatisfactory response rates. The poor prognosis of patients with metastatic TNBC justifies intensive research on new drugs for this group of patients, including attempts to use conjugates. This article discusses the reports on sacituzumab govitecan (SG), which is composed of a monoclonal antibody targeting trophoblast-cell surface antigen 2 (Trop-2) expressed on many TNBC cells and linked to a payload (SN-38), the active metabolite of irinotecan. The structure and mechanism of action of this conjugate are presented. The available results of clinical trials with SG in breast cancer patients are summarized, including the results of the ASCENT registration study, which showed a significant improvement in the median progression-free survival, as well as overall survival, compared to classic chemotherapy in patients previously treated with advanced TNBC. The most common side effects of the drug are discussed, indicating principles of primary and secondary prophylaxis that allow for effective management of possible complications. Directions for further research in breast cancer patients on this very promising conjugate were also indicated.

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Keywords

sacituzumab govitecan; triple-negative breast cancer; conjugate; Trop-2

About this article
Title

Sacituzumab govitecan — a new therapy for patients with triple-negative breast cancer

Journal

Oncology in Clinical Practice

Issue

Ahead of print

Article type

Review paper

Published online

2022-07-01

Page views

133

Article views/downloads

81

DOI

10.5603/OCP.2022.0003

Keywords

sacituzumab govitecan
triple-negative breast cancer
conjugate
Trop-2

Authors

Katarzyna Pogoda
Agnieszka Jagiełło-Gruszfeld
Anna Niwińska
Zbigniew Nowecki

References (22)
  1. Hortobagyi GN, Stemmer SM, Burris HA, et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021; 32: S1290–S1291.
  2. Swain SM, Miles D, Kim SB, et al. CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020; 21(4): 519–530.
  3. Rugo HS, Cortés J, Cescon DW, et al. LBA16 - KEYNOTE-355: Final results from a randomized, double-blind phase III study of first-line pembrolizumab + chemotherapy vs placebo + chemotherapy for metastatic TNBC. Ann Oncol. 2021; 32(suppl_5): S1283–S1346.
  4. Emens LA, Adams S, Barrios CH, et al. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Ann Oncol. 2021; 32(8): 983–993.
  5. Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020; 31(12): 1623–1649.
  6. Gennari A, André F, Barrios CH, et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021; 32(12): 1475–1495.
  7. Pogoda K, Niwińska A, Murawska M, et al. Analysis of pattern, time and risk factors influencing recurrence in triple-negative breast cancer patients. Med Oncol. 2013; 30(1): 388.
  8. Ramesh M, Ahlawat P, Srinivas NR. Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010; 24(1): 104–123.
  9. Goldenberg DM, Cardillo TM, Govindan SV, et al. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget. 2015; 6(26): 22496–22512.
  10. Zhao W, Kuai X, Zhou X, et al. Trop2 is a potential biomarker for the promotion of EMT in human breast cancer. Oncol Rep. 2018; 40(2): 759–766.
  11. Ambrogi F, Fornili M, Boracchi P, et al. Trop-2 is a determinant of breast cancer survival. PLoS One. 2014; 9(5): e96993.
  12. Bardia A, Mayer IA, Diamond JR, et al. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2017; 35(19): 2141–2148.
  13. Bardia A, Hurvitz SA, Tolaney SM, et al. ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021; 384(16): 1529–1541.
  14. Starodub AN, Ocean AJ, Shah MA, et al. First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Clin Cancer Res. 2015; 21(17): 3870–3878.
  15. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2019; 380(8): 741–751.
  16. Diéras V, Weaver R, Tolaney S, et al. Abstract PD13-07: Subgroup analysis of patients with brain metastases from the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in metastatic triple-negative breast cancer. Poster Spotlight Session Abstracts. 2021.
  17. Bardia A, Tolaney SM, Punie K, et al. Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. Ann Oncol. 2021; 32(9): 1148–1156.
  18. Kalinsky K, Oliveira M, Traina T, et al. Outcomes in patients (pts) aged ≥65 years in the phase 3 ASCENT study of sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC). J Clin Oncol. 2021; 39(15_suppl): 1011–1011.
  19. Rugo H, Tolaney S, Loirat D, et al. Abstract PS11-09: Impact ofUGT1A1status on the safety profile of sacituzumab govitecan in the phase 3 ASCENT study in patients with metastatic triple-negative breast cancer. Poster Session Abstracts. 2021.
  20. Loibl S, Loirat D, Tolaney SM, et al. 257P Health-related quality of life (HRQoL) in the ASCENT study of sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC). Ann Oncol. 2021; 32: S472–S473.
  21. Charakterystyka Produuktu Leczniczego Trodelvy. Trodelvy, INN-sacituzumab govitecan. europa.eu (15.01.2022).
  22. Kalinsky K, Diamond JR, Vahdat LT, et al. Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020; 31(12): 1709–1718.

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