Dr Sara M. Tolaney: Standard of Care, Novel Approaches for Treatment of HER2-Positive Breast Cancer

There are a lot of new and exciting agents that are being explored for metastatic HER2-positive disease, explained Sara M. Tolaney, MD, MPH, instructor of medicine, Harvard Medical School, attending physician of medical oncology, Dana-Farber Cancer Institute.

What’s the current standard of care for HER2-positive breast cancer?
In the metastatic setting, generally, we start out using a taxane with trastuzumab and pertuzumab, and then upon progression, we go on to trastuzumab DM1, and then thereafter, it’s really chemotherapy combined with anti-HER2 therapy. In patients who have hormone-receptor-positive HER2-positive disease, we sometimes will integrate endocrine therapy with dual anti-HER2 therapy along the course of their therapy.

What novel approaches are being taken for the treatment of HER2-positive breast cancer?
There are a lot of new and exciting agents that are being explored for metastatic HER2-positive disease. I think one particular class that’s exciting are the antibody-drug conjugates. So, there’s one agent, the DS-8201a agent. So, it’s an antibody-drug conjugate targeting HER2, and it delivers a topoisomerase 1 payload. They’ve demonstrated about a 60% objective response in metastatic HER2-positive breast cancer, and they uniquely even have activity in HER2-low-positive tumors, with about a 30% response.

Outside of that agent, which is made by Daiichi, there’s several other antibody-drug conjugates. So, here we saw results from a trial looking at SYD985, which is an antibody-drug conjugate that delivers a DNA alkylator payload, and they demonstrated a little over a 30% objective response in pretreated HER2-positive disease. Those 2 agents, along with several other antibody-drug conjugates that are coming along, including now even bispecific antibody-drug conjugates, I think, may really be a great opportunity for a lot of our patients, because you could imagine these agents may either be better than T-DM1 and replace it in the second line setting, or could work in T-DM refractory patients, and so really move into the third line setting.
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