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FDA Approves Margenza for Treatment of Metastatic HER2-Positive Breast Cancer

Web Exclusives - Breast Cancer, FDA Updates

On December 16, 2020, the FDA approved margetuximab-cmkb (Margenza; MacroGenics) in combination with chemotherapy for the treatment of adults with metastatic HER2-positive breast cancer who have received ≥2 previous anti-HER2 regimens, of which at least 1 was for metastatic disease. The application for this approval received a fast-track designation.

“As the only HER2-targeted agent to have shown a PFS improvement versus trastuzumab 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,” said Hope S. Rugo, MD, Director of Breast Oncology and Clinical Trials Education, University of California San Francisco Helen Diller Family Comprehensive Cancer Center.

The FDA approved margetuximab based on SOPHIA, a randomized, multicenter, phase 3 clinical trial that included 536 patients with IHC (immunohistochemistry)3-positive or ISH (in situ hybridization)-amplified HER2-positive metastatic breast cancer who had received previous treatment with other anti-HER2 therapies.

Patients were randomized in a 1:1 ratio to margetuximab plus chemotherapy or to trastuzumab (Herceptin) plus chemotherapy. People were stratified to treatment groups by the choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine), the number of lines of therapy received in the metastatic setting (≤2 or >2), and the number of metastatic sites (≤2 or >2).

The primary end points were progression-free survival (PFS) and overall survival (OS). The secondary end points were objective response rate (ORR) and duration of response (DOR).

The median PFS in the margetuximab arm was 5.8 months (95% confidence interval [CI], 5.5-7) compared with 4.9 months (95% CI, 4.2-5.6) in the control arm (hazard ratio, 0.76; 95% CI, 0.59-0.98; P = .033). The confirmed ORR was 22% (95% CI, 17-27), with a median DOR of 6.1 months (95% CI, 4.1-9.1) in the margetuximab arm versus an ORR of 16% (95% CI, 12-20) in the control arm and a median DOR of 6 months (95% CI, 4.0-6.9).

The most common (>10%) adverse reactions with margetuximab plus chemotherapy were fatigue or asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia or myalgia, cough, decreased appetite, dyspnea, infusion-related reactions, palmar-plantar erythrodysesthesia, and extremity pain. Treatment with margetuximab is associated with the risks for left-ventricular dysfunction and embryo-fetal toxicity.

The recommended dose of margetuximab is 15 mg/kg by intravenous infusion over 120 minutes for the initial dose, then over a minimum of 30 minutes every 3 weeks.

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Last modified: April 15, 2021