Dr. Rugo on the Utility of Margetuximab in HER2+ Metastatic Breast Cancer

Hope S. Rugo, MD, a professor in the Department of Medicine, Hematology/Oncology, and director, Breast Oncology and Clinical Trials Education, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discusses the utility of margetuximab in HER2-positive metastatic breast cancer.

Margetuximab plus chemotherapy led to a 29% reduction in the risk of disease progression or death versus trastuzumab (Herceptin) plus chemotherapy in the phase III SOPHIA trial. In December 2019, the developers of the HER2-positive antibody submitted a biologics license application for the drug for use in combination with chemotherapy as a treatment for patients with metastatic HER2-positive breast cancer.

Polymorphisms in the IgG Fc gamma receptor have the potential to limit the activity of trastuzumab. However, margetuximab is an Fc engineered HER2-positive antibody designed to enhance IgG1 Fc affinity for the activating Fc gamma receptor and decrease affinity for the inhibitory Fc gamma receptor, explains Rugo.

According to a prespecified exploratory analysis, patients who harbored a CD16A 158F allele had a median overall survival of 23.7 months with margetuximab versus 19.4 months with trastuzumab. These data merit additional investigation of the agent as neoadjuvant therapy in patients with low-affinity IgG Fc gamma receptors, says Rugo.

It remains to be seen how margetuximab might fit into the landscape given the recent approval of fam-trastuzumab deruxtecan-nxhi (Enhertu) and the potential approval of tucatinib in the metastatic setting, concludes Rugo.