Dr. Gradishar on the Expanding Role of Trastuzumab Deruxtecan in HER2+ Breast Cancer

William J. Gradishar, MD, chief of hematology and oncology, Department of Medicine; Betsy Bramsen Professorship of Breast Oncology; and a professor of medicine (hematology and oncology) at Northwestern University Feinberg School of Medicine, discusses the expanding role of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive breast cancer.

Trastuzumab deruxtecan is an antibody-drug conjugate (ADC) that has a similar mechanism ​of action as ado-trastuzumab emtansine (T-DM1; Kadcyla), Gradishar explains. ​Trastuzumab deruxtecan contains the monoclonal antibody trastuzumab ​(Herceptin), which binds to HER2, a ​stable linker and a cytotoxic payload.

However, trastuzumab deruxtecan has a greater number of payloads per antibody compared with T-DM1, ​says Gradishar.

Notably, trastuzumab deruxtecan has been a ​welcome addition to the HER2-positive breast cancer armamentarium, ​Gradishar says. The agent is current being evaluated in a head-to-head trial with T-DM1 to determine how the agents compare in terms of efficacy and safety.

In several studies, trastuzumab deruxtecan demonstrated meaningful clinical activity in patients, including those who received prior T​-DM1. Now, the agent is approved for use in the metastatic setting, Gradishar concludes.