This transcript has been edited for clarity.
Happy holidays, everyone. This is Dr Kathy Miller from Indiana University.
I want to make sure you've had a chance to think carefully about the margetuximab approval by the US Food and Drug Administration (FDA).
Margetuximab is a HER2-targeted monoclonal antibody that is similar to trastuzumab. With margetuximab, the Fc domain (the part that interacts with the immune system) has been altered to be more attractive to the immune system, as a way of stimulating more antibody-dependent cellular cytotoxicity. The goal is that this will both inhibit HER2 signaling and create greater engagement of the immune system.
Margetuximab was FDA-approved on the basis of the SOPHIA trial.
Enrolled patients had received at least two previous HER2-targeted therapies for metastatic breast cancer. All of the 536 patients had been given trastuzumab; all but one had received pertuzumab; and 91% had previous therapy with T-DM1 [ado-trastuzumab emtansine].
Patients were randomly assigned to trastuzumab and chemotherapy or margetuximab and chemotherapy. Chemotherapy was a menu of reasonable single-agent options: capecitabine, eribulin, vinorelbine, or gemcitabine.
The trial met its primary endpoint, with an improvement in progression-free survival (PFS) that reached statistical significance. However, I would argue that the improvement in PFS did not reach clinical significance. The difference was 4.9 months compared with 5.8 months. We’re talking about an improvement in PFS with margetuximab of 20 days to maybe 25 days. Response rates also improved from 16% to 22%.
We certainly are not finished treating patients with HER2+ disease. The potential to achieve greater immune activity is real, and possibly in patients with earlier-stage disease, this agent will have greater activity. Perhaps it's a better partner when combining HER2-targeted therapy with some of our novel immuno-oncology agents. But in my mind, a 0.9% improvement in PFS is simply not enough. Our patients need more, and our patients demand more. And we, as a community, should demand more.
I welcome your thoughts on the future of this agent. I'll see you again soon.
Kathy D. Miller, MD, is associate director of clinical research and co-director of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University. Her career has combined both laboratory and clinical research in breast cancer.
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Cite this: Kathy D. Miller. Margetuximab for HER2+ Metastatic Breast Cancer Falls Short - Medscape - Jan 07, 2021.
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