Margetuximab-cmkb was approved, in combination with chemotherapy, for the treatment of metastatic HER2-positive breast cancer in adult patients who have received ≥2 previous anti-HER2 treatments, of which ≥1 were for the treatment of metastatic disease. US Food and Drug Administration approval of this monoclonal antibody occurred in December 2020.1
SOPHIA was a randomized, multicenter, open-label efficacy trial of patients (N = 536) with immunohistochemistry 3+ or in situ hybridization-amplified HER2-positive metastatic breast cancer who had received prior treatment with other anti-HER2 therapies. Patients were randomized (1:1) to receive either trastuzumab plus chemotherapy or margetuximab plus chemotherapy. The randomization was stratified by 3 additional variables: choice of chemotherapy (ie, capecitabine, eribulin, gemcitabine, or vinorelbine), number of lines of therapy in the metastatic setting (≤2, >2), and number of metastatic sites (≤2, >2).
Progression-free survival (PFS) by blinded independent central review (BICR) and overall survival were the main efficacy outcome measures. Objective response rate (ORR) and duration of response (DOR) assessed by BICR were additional efficacy outcome measures.
Median PFS was 4.9 months in the control arm, compared with 5.8 months in the margetuximab arm.
In the control arm, the confirmed ORR was 16% and the median DOR was 6.0 months, compared with the margetuximab arm that had a confirmed ORR of 22% and a median DOR of 6.1 months.
In patients treated with margetuximab in combination with chemotherapy, the most common adverse drug reactions appearing at a rate of >10% were abdominal pain, alopecia, arthralgia/myalgia, constipation, cough, decreased appetite, diarrhea, dyspnea, extremity pain, fatigue, headache, infusion-related reactions, palmar-plantar erythrodysesthesia, peripheral neuropathy, pyrexia, nausea, and vomiting. A boxed warning regarding the risks of left ventricular dysfunction and embryo-fetal toxicity is included in the margetuximab prescribing information.
When initiating therapy, the suggested margetuximab dose is 15 mg/kg to be administered via intravenous infusion over 2 hours, and then for all subsequent doses over a minimum of 30 minutes every 3 weeks. Margetuximab may be administered without delay after chemotherapy completion on days when both margetuximab and chemotherapy are to be dispensed.
US Food and Drug Administration. FDA approves margetuximab for metastatic HER2-positive breast cancer. Published December 17, 2020. www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-margetuximab-metastatic-her2-positive-breast-cancer. Accessed March 28, 2021.
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