Sacituzumab for the treatment of triple-negative breast cancer: the poster child of future therapy?

ABSTRACT

Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that disproportionately impacts younger women and is associated with a poor prognosis. Systemic treatment options for metastatic TNBC (mTNBC) are limited to cytotoxic chemotherapy agents with low response rates. This encouraged the clinical development of sacituzumab govitecan (IMMU-132), an antibody-drug conjugate targeting Trop-2, a potential target in epithelial cancer such as TNBC.

Areas covered: We summarize the key features, pharmacokinetics, and the safety and efficacy data of sacituzumab govitecan. We also discuss the future directions of this novel therapeutic agent for mTNBC.

Expert opinion: Based on the efficacy and tolerability observed in the phase 1/2 clinical trial, sacituzumab govitecan was granted breakthrough therapy designation by the Food and Drug Administration as ≥3^rd line therapy for mTNBC. Novel treatment modalities for the management of mTNBC are necessary to improve the care of this aggressive disease. Sacituzumab govitecan represents an important advance in the treatment of mTNBC because of its efficacy and tolerability.

KEYWORDS:

• Antibody–drug conjugate
• IMMU-132
• metastatic breast cancer
• sacituzumab govitecan
• triple-negative breast cancer
• TNBC

Box 1. Drug summary.

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Article highlights

• Metastatic triple-negative breast cancer (mTNBC) carries a poor prognosis.

• Systemic treatment modalities for mTNBC are currently limited to cytotoxic chemotherapy.

• Antibody–drug conjugates (ADCs) link cytotoxic agents to monoclonal antibodies that target specific cells and allow for selective delivery, potentially reducing toxicity and increasing efficacy.

• Sacituzumab govitecan (IMMU-132) is an ADC that targets delivery of SN-38 to Trop-2 which is expressed on epithelial cancer cells including TNBC.

• Clinical evidence supports the safety and efficacy of sacituzumab govitecan in pretreated mTNBC.

This box summarizes key points contained in the article.

Declaration of interest

L Spring has disclosed consulting fees from Novartis and institutional research funding from Tesaro.

A Nagayama has disclosed stock options in Chugai pharmaceuticals.

A Bardia has disclosed consulting fees from Genentech/Roche, Immunomedics, Novartis, Pfizer, Merck, Radius Health, Spectrum Pharma and Taiho Pharma, a research grant from Biothernostics and institutional funding from Genentech/Roche, Immunomedics, Novartis, Pfizer, Merck, Radius Health, Sanofi and Mersana Pharmaceuticals. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the National Cancer Institute (NCI) and the Susan G Komen Foundation. A Bardia received funding support from NCI grant K12 CA087723 and a Susan G Komen Foundation grant CCR15224703. L Spring has received funding support from NCI grant KL2 TR001100.