Drug Evaluation

*Author for correspondence: Tel.: +49 6102 7480 350;

https://orcid.org/0000-0003-1693-8557

German Breast Group, Neu-Isenburg, 63263, Germany

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Frederik Marmé

Medical Faculty Mannheim, Heidelberg University, Universitätsfrauenklinik, Mannheim, 68167, Germany

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Sibylle Loibl

German Breast Group, Neu-Isenburg, 63263, Germany

Centre for Haematology & Oncology, Bethanien, Frankfurt/M, 60389, Germany

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Published Online:7 Sep 2022https://doi.org/10.2217/fon-2022-0407

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Abstract

Sacituzumab govitecan (SG) is a new antibody–drug conjugate directed against the cell-surface antigen Trop-2. Characteristics of the linker connecting the payload SN-38 to the antibody allows SG to kill tumor cells expressing Trop-2 and also the adjacent tumor cells (bystander effect). SG showed efficacy and safety in several epithelial tumors. The phase III ASCENT trial led to the approval of SG (10 mg/kg, d1,8 q3w) in patients with advanced or metastatic triple-negative breast cancer (TNBC) who have received ≥2 prior systemic therapies, including ≥1 for metastatic disease. The phase III TROPiCS-02 trial in heavily pretreated advanced hormone receptor (HR)-positive breast cancer has recently shown an improvement in progression-free survival for patients treated with SG compared to single-agent chemotherapy. The phase III post-neoadjuvant SASCIA study in early high-risk TNBC and HR-positive breast cancer is currently recruiting patients.

Plain language summary

Sacituzumab govitecan is a new treatment for metastatic triple-negative breast cancer. Triple-negative means that the three most commonly identified proteins are not found on the surface of cancer cells (estrogen or progesterone receptor and high level of the protein HER2). Metastatic breast cancer indicates that the breast cancer has spread to other parts of the body. Sacituzumab govitecan is a monoclonal antibody, a therapeutic antibody or protein that can attach a specific target on the surface of cancer cells known as Trop-2. The antibody carries a medication known as SN-38, which is released within and around the cancer cells, causing the destruction of cancer cells. The ASCENT trial compared 3 acituzumab govitecan with chemotherapy, which is a treatment that kills cancer cells or stops them from dividing. The trial showed that patients with advanced triple-negative breast cancer who took sacituzumab govitecan lived longer than those who took a different chemotherapy regimen while on the study. The TROPiCS-02 trial showed that also patients with a metastatic cancer expressing estrogen or progesterone receptor, known as hormone-receptor positive breast cancer, derived benefit from sacituzumab govitecan. The SASCIA trial will define if patients with early breast cancer receiving sacituzumab govitecan after surgery might live longer without the recurrence of cancer. Early-stage breast cancer means that the cancer has not spread to other parts of the body and can be completely removed with surgery.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 18, No. 28

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Received 19 April 2022

Accepted 27 July 2022

Published online 7 September 2022

Published in print September 2022

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Author contributions

All authors made a substantial contribution to the conception of the work; all authors drafted the work and revised it critically for important intellectual content; all authors approved the final version of the manuscript to be published; all authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Financial & competing interests disclosure

JF reported to be employee of the GBG Forschungs GmbH. GBG Forschungs GmbH received funding for research grants from Abbvie, AstraZeneca, BMS, Daiichi-Sankyo, Gilead, Novartis, Pfizer and Roche (paid to the institution). FM reports personal fees from Gilead/Immunomedics Roche, AstraZeneca, Pfizer, Tesaro, Novartis, Amgen, PharmaMar, GenomicHealth, CureVac, EISAI, Celegene, Clovis, Janssen-Cilag, GSK, MSD, Seagen, Myriad, Pierre-Fabre, outside the submitted work. Dr. Loibl reports grants and other from Abbvie, other from Amgen, grants and other from AstraZeneca, other from Bayer, other from BMS, grants and other from Celgene, grants, non-financial support and other from Daiichi-Sankyo, other from Eirgenix, other from GSK, grants, non-financial support and other from Immunomedics/Gilead, other from Lilly, other from Merck, grants, non-financial support and other from Novartis, grants, non-financial support and other from Pfizer, other from Pierre Fabre, other from Prime/Medscape, non-financial support and other from Puma, grants, non-financial support and other from Roche, other from Samsung, non-financial support and other from Seagen, outside the submitted work; In addition, Dr. Loibl has a patent EP14153692.0 pending, a patent EP21152186.9 pending, a patent EP15702464.7 issued, a patent EP19808852.8 pending, and a patent Digital Ki67 Evaluator with royalties paid. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Sacituzumab govitecan: past, present and future of a new antibody–drug conjugate and future horizon

Abstract

Plain language summary

References