Margenza-Chemo Combo Approved by FDA for Patients with Previously Treated Metastatic HER2-Positive Breast Cancer

The Food and Drug Administration on Wednesday approved Margenza (margetuximab-cmkb) in combination with chemotherapy for the treatment of adults with metastatic HER2-positive breast cancer who have received at least two prior anti-HER2 treatment regimens, according to the agent’s manufacturer, MacroGenics.

“The approval of Margenza is an exciting milestone for MacroGenics and, more importantly, it brings a new treatment option to metastatic breast cancer patients. We are grateful for the patients who participated in this study, as well as their families, and everyone who played a role in helping MacroGenics reach this milestone,” the company’s president and CEO Dr. Scott Koenig said in a press release.

The agency based its decision on data from the randomized, open-label phase 3 SOPHIA trial, which was comprised of 536 patients with metastatic HER2-positive breast cancer who have previously been treated with anti-HER2-targeted therapies.

Each patient enrolled on the study had previously received Herceptin (trastuzumab), all but one had received prior treatment Perjeta (pertuzumab), and 91% had previously received Kadcyla (ado-trastuzumab emtansine).

Patients were randomized to either receive Margenza (266 patients) intravenously every three weeks or Herceptin (270 patients) also administered intravenously every three weeks in combination with one of capecitabine, eribulin, gemcitabine or vinorelbine.

Measuring progression-free survival (time from treatment to disease progression) and overall survival were the main goals of the study. Additional goals of the study included objective response rates and duration of responses.

Margenza plus chemotherapy significantly reduced the risk of disease progression or death by 24% in the study population, compared with Herceptin plus chemotherapy. The median progression-free survival was 5.8 months in the group who received the Margenza-based regimen and 4.9 months in those who received the Herceptin-based regimen.

The Margenza-based treatment elicited an objective response rate (the proportion of patients who had a complete or partial response to treatment) of 22% in patients, compared to 16% in those who received the Herceptin-based treatment. Final overall survival data is expected to be available later in 2021.

The most common side effects to occur in patients who received the Margenza combination included fatigue (57%), nausea (33%), diarrhea (25%) and vomiting (21%). There is a boxed warning for left ventricular dysfunction and embryo-fetal toxicity associated attached to the approval.

“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,” Dr. Hope S. Rugo, professor of medicine and director of Breast Oncology and Clinical Trials Education at University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, said in the release. “As the only HER2-targeted agent to have shown a PFS improvement versus (Herceptin) in a head-to-head phase 3 clinical trial, Margenza with chemotherapy represents the newest treatment option for patients who have progressed on available HER2-directed therapies.”

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