FDA Approval Summary: Margetuximab plus Chemotherapy for Advanced or Metastatic HER2-Positive Breast Cancer.

Abstract

On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combination with chemotherapy, for the treatment of adult patients with HER2-positive (HER2+) metastatic breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Approval was based on data from SOPHIA, a multicenter, randomized, open-label, active controlled study comparing margetuximab with trastuzumab, in combination with chemotherapy. The primary efficacy endpoint was progression-free survival (PFS) by blinded independent central review. SOPHIA demonstrated a 0.9-month difference in median PFS between the two treatment arms [5.8 vs. 4.9 months, respectively; stratified HR, 0.76 (95% confidence interval: 0.59-0.98; P = 0.0334)]. Overall survival (OS) was immature at the data cut-off date of September 10, 2019. Infusion-related reactions (IRR) are an important safety signal associated with margetuximab plus chemotherapy. In SOPHIA, 13% of patients treated with margetuximab plus chemotherapy reported IRRs, of which 1.5% were grade 3. The most commonly reported adverse drug reactions (>10%) with margetuximab in combination with chemotherapy were fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, IRR, palmar-plantar erythrodysesthesia, and extremity pain. Overall, the favorable risk-benefit profile for margetuximab when added to chemotherapy supported its approval for the intended indication.

• Authors: Melanie Royce, Christy L Osgood, Anup K Amatya, Mallorie H Fiero, C J George Chang, Tiffany K Ricks, Krithika A Shetty, Jeffrey Kraft, Junshan Qiu, Pengfei Song, Rosane Charlab, Jingyu Yu, Kathryn E King, Anshu Rastogi, Brian Janelsins, Wendy C Weinberg, Kathleen Clouse, Vicky Borders-Hemphill, Lindsey Brown, Candace Gomez-Broughton, Zhong Li, Thuy Thanh Nguyen, Zhihao Qiu, Anh-Thy Ly, Suyoung Chang, Tingting Gao, Chi-Ming Tu, Bellinda King-Kallimanis, William F Pierce, Kelly Chiang, Clara Lee, Kirsten B Goldberg, John K Leighton, Shenghui Tang, Richard Pazdur, Julia A Beaver, Laleh Amiri-Kordestani
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 8 Pg. 1487-1492 (04 14 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 34916216 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal
• Receptor, ErbB-2
• margetuximab
• Trastuzumab

Topics

• Adult
• Antibodies, Monoclonal (adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (pathology)
• Drug Approval
• Female
• Humans
• Receptor, ErbB-2 (therapeutic use)
• Trastuzumab (adverse effects)