Dr. Rugo on the Impact of Margetuximab Based on CD16A Fc Receptors in HER2+ 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 impact of margetuximab in patients with HER2-positive metastatic breast cancer who have an F allele versus V allele, according to findings of the phase III SOPHIA trial.

While examining the impact of the IgG Fc gamma receptor differences on the activity of margetuximab, it was observed that there are 2 variants with the CD16A Fc receptor: the F allele and the V allele, explains Rugo. Data have already shown that the addition of trastuzumab (Herceptin) to chemotherapy in patients who had the high-affinity allele benefited the most from trastuzumab; however, there was a decreasing benefit if patients had FV or FF, says Rugo.

Rugo hypothesized that patients who carried the F allele would have better responses to margetuximab. When looking at overall survival (OS) based on patients who had the F allele, FF or FE, there was a bigger difference in OS with an absolute difference of 4.3 months, which was not statistically significant with a P value of .08, according to Rugo.

Meanwhile, when looking at patients who are homozygous for V, patients randomized to margetuximab had much worse disease, including more brain metastases, visceral metastases, and other poor-prognostic features, concludes Rugo.