Abstract
Several anti-HER2 agents are approved for third-line treatment and beyond (after first-line and second-line); however, no specific treatment strategy is recommended for third-line and beyond. Although these agents improve disease outcomes, HER2-positive metastatic breast cancer remains incurable and there is an unmet need for effective therapies in the later line setting. This review focuses on the development of margetuximab-cmkb, a novel, Fc-engineered, anti-HER2 monoclonal antibody, and its role in the systemic treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Plain language summary - A new treatment option for patients with HER2-positive metastatic breast cancer In about 20% of patients with breast cancer, their tumor cells make too many copies of a protein called HER2. We call them HER2-positive breast cancer cells. HER2 is a protein that signals to breast cancer cells to make them grow. Certain drugs, known as antibodies, are able to bind to the HER2 proteins on the surface of the tumor cells. This stops their signaling and slows down the growth of the tumor cells. These antibodies are called anti-HER2 antibodies. In addition to its 'head' region binding to HER2, the 'tail' region of the anti-HER2 antibody can bind to certain other proteins (receptors) found on the surface of immune cells. When the anti-HER2 antibodies bind to the receptors on immune cells, this starts an anticancer immune response against the HER2-positive breast cancer cells and kills them. This review explains how anti-HER2 antibodies may block and destroy HER2-positive breast cancer cells. In particular, we focus on the beneficial and adverse effects of margetuximab, an anti-HER2 antibody. The tail region of margetuximab has been changed to boost the immune responses against HER2-positive cancer cells. Margetuximab is approved in the USA for patients with HER2-positive metastatic breast cancer after they have already received two or more anti-HER2 therapies. The decision to approve this was based on the pivotal clinical trial SOPHIA.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1099-1112 |
| Number of pages | 14 |
| Journal | Future Oncology |
| Volume | 19 |
| Issue number | 16 |
| DOIs | |
| State | Published - May 1 2023 |
Funding
This literature review and manuscript were sponsored by MacroGenics. WJ Gradishar has received consulting fees from AstraZeneca, Daiichi Sankyo, Merck, and Seagen. R O'Regan has received grants from Novartis; consulting fees and honoraria from Pfizer, Genomic Health, Biotheranostics, Novartis, Lilly, Puma Biotechnology, Genentech, Immunomedics, and MacroGenics; and financial support for attending ASCO, AACR, and ESHOS. MF Rimawi has received a grant from Pfizer, consulting fees from Novartis, Genentech, AstraZeneca, SeaGen; and honoraria from MacroGenics for an advisory board. JL Nordstrom is an employee and stockholder of MacroGenics. MK Rosales was an employee and stockholder of MacroGenics at the time of study conduct. HS Rugo has received research support for clinical trials through the University of California from Pfizer, Merck, Novartis, Lilly, Roche, Daiichi Sankyo, Seattle Genetics, MacroGenics, Sermonix, Boehringer Ingelheim, Polyphor, AstraZeneca, Ayala, Astellas, and Gilead; and honoraria from Puma, Samsung, Mylan, Chugai Pharma, Blueprint Medicines, and Napo 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 apart from those disclosed.
Keywords
- Fc engineering
- FcγRIIIA genotype
- clinical trial
- human epidermal growth factor receptor 2
- margetuximab
- metastatic breast cancer
- monoclonal antibody
ASJC Scopus subject areas
- Oncology
- Cancer Research
