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Margenza in combination with chemotherapy for metastatic HER2-positive breast cancer, approved by FDA

The Food and Drug Administration ( FDA ) has approved Margenza ( Margetuximab-cmkb; Margetuximab ) in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.

Efficacy was evaluated in SOPHIA, a randomized, multicenter, open-label trial of 536 patients with IHC 3+ or ISH-amplified HER2+ metastatic breast cancer who had received prior treatment with other anti-HER2 therapies.
Patients were randomized ( 1:1 ) to Margetuximab plus chemotherapy or Trastuzumab plus chemotherapy. Randomization was stratified by chemotherapy choice ( Capecitabine, Eribulin, Gemcitabine, or Vinorelbine ), number of lines of therapy in the metastatic setting ( 2 or less, more than 2 ), and number of metastatic sites ( 2 or less, more than 2 ).

The main efficacy outcome measures were progression-free survival ( PFS ) by blinded independent central review ( BICR ) and overall survival ( OS ).
Additional efficacy outcome measures were objective response rate ( ORR ) and duration of response ( DOR ) assessed by BICR.

Median progression-free survival in the Margetuximab arm was 5.8 months ( 95% CI: 5.5, 7.0 ) compared with 4.9 months ( 95% CI: 4.2, 5.6 ) in the control arm ( hazard ratio, HR 0.76; 95% CI: 0.59, 0.98; p=0.033 ).
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 compared to an ORR of 16% ( 95% CI: 12, 20 ) and median DOR of 6.0 months ( 95%CI: 4.0, 6.9 ) in the control arm.

The most common adverse drug reactions ( more than 10% ) with Margetuximab in combination with chemotherapy are fatigue / asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, infusion-related reactions, palmar-plantar erythrodysesthesia, and extremity pain.

The Prescribing Information includes a Boxed Warning to advise health professionals of the risks of left ventricular dysfunction and embryo-fetal toxicity.

The recommended Margetuximab dose is 15 mg/kg by intravenous infusion over 120 minutes for the initial dose, then over a minimum of 30 minutes every 3 weeks for all subsequent doses.
On days when both Margetuximab and chemotherapy are to be administered, Margetuximab may be administered immediately after chemotherapy completion. ( Xagena )

Source: FDA, 2020