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WASHINGTON -- The FDA approved the anti-HER2 antibody margetuximab (Margenza) as third-line treatment for metastatic HER2-positive breast cancer.

The approval stipulates use of margetuximab with chemotherapy. The antibody is the first HER2-targeted therapy to improve progression-free survival (PFS) versus trastuzumab (Herceptin), when both agents were used in combination with chemotherapy, according to a from drugmaker MacroGenics.

"Early detection and treatment have had a positive impact on the survival of patients with breast cancer, but the prognosis for people diagnosed with metastatic breast cancer remains poor, and additional treatments are needed," Hope S. Rugo, MD, of the University of California San Francisco, said in the statement.

Support for the approval came primarily from the phase III randomized SOPHIA trial (led by Rugo) involving 536 patients with HER2-positive breast cancer previously treated with trastuzumab, pertuzumab (Perjeta), and T-DM1 (Kadcyla). Patients were randomized to trastuzumab or margetuximab, both in combination with chemotherapy.

The trial had sequential co-primary endpoints of PFS and overall survival (OS). The PFS analysis showed a small but statistically significant 0.9-month improvement in favor of margetuximab, which then triggered an OS analysis. The first OS analysis yielded a nonsignificant 1.8-month advantage (21.6 vs 19.8 months) for margetuximab.

Prespecified exploratory analyses of immune-activating CD16A genotype showed larger PFS and OS benefits for margetuximab among carriers of the 158F allele (FF or FV), which accounts for more than 80% of breast cancers. The final OS analysis is expected by mid-2021.

The most common adverse events (>20% of patients) with margetuximab plus chemotherapy were fatigue/asthenia (57%), nausea (33%), diarrhea (25%), and vomiting (21%). Additionally, infusion-related reactions occurred in 13% of patients, reported as grade 2 or less in most cases. Prescribing information for margetuximab includes a boxed warning about risk of left ventricular dysfunction and embryo-fetal toxicity.

According to the MacroGenics statement, commercial shipments are expected to begin in March.

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