Clinical development and current role of margetuximab for the treatment of breast cancer.

Up to 20% of breast cancers overexpress HER2, a molecular alteration conferring these tumors a particularly aggressive behavior. However, targeting HER2 has radically changed the prognosis of this disease in the last 2 decades, with multiple anti-HER2 compounds shown to improve disease outcomes both in the early and advanced setting. The latest anti-HER2 compound to be approved by the U.S. Food and Drug Administration (FDA) was margetuximab, an Fc-engineered monoclonal antibody with an improved binding to FcγRIIIA receptor, which leads to a greater antibody-dependent cellular cytotoxicity (ADCC) activation compared with trastuzumab. Margetuximab was shown to slightly improve progression-free survival compared with trastuzumab when combined with chemotherapy for the treatment of advanced HER2-positive breast cancer patients, and is now included among the available treatment options for pretreated HER2-positive breast cancer patients. In this monograph we recapitulate the clinical development, current role and future perspectives of margetuximab for the treatment of breast cancer.