Ian E. Krop, MD, PhD

Ian E. Krop, MD, PhD, of Dana-Farber Cancer Institute, Boston, said that margetuximab is one of three new “exciting” drugs in the HER2-positive setting with different mechanisms of action; the other two are tucatinib and trastuzumab deruxtecan.

“Margetuximab is a modified version of trastuzumab that appears to increase the immune effects of trastuzumab,” he said. “While the benefits were modest, there was little added toxicity, so in those later-line patients with the low affinity DC16A allele, it would seem to be a potentially useful option. It is also hoped that the benefits of margetuximab may be more pronounced in the early disease setting in which patients’ immune systems are more intact, and this is a question that should be evaluated in clinical trials.”

Angela M. DeMichele, MD, MSCE

Carlos L. Arteaga, MD

Angela M. DeMichele, MD, MSCE, of the Perelman School of Medicine, University of Pennsylvania, Philadelphia, said: “We hoped we could exploit the ability of margetuximab to increase the affinity for the CD16A allele to make the drug more effective. It’s not clear that it worked. I don’t know if there will be a role for this drug, because we have so many drugs for HER2-positive disease.”

“Margetuximab had a modest survival benefit in HER2-positive patients with this unique polymorphism [ie, the CD16A-158F allele]. It might turn out to be an option for patients who have disease progression after trastuzumab and express that polymorphism,” said Carlos L. Arteaga, MD, Director of The University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center, Dallas.