Dr Foldi on the Evolving Treatment Landscape of ADCs in HER2+ Breast Cancer

Julia Foldi, MD, PhD, assistant professor of medicine, Hematology/Oncology, Department of Medicine, University of Pittsburg Medical Center (UPMC), University of Pittsburg Medical Center, breast medical oncologist, discusses the evolving role of antibody-drug conjugates (ADCs) in the treatment paradigm for metastatic HER2-positive breast cancer.

In multiple large, randomized phase 3 clinical trials, including the series of DESTINY-Breast trials, both fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) and sacituzumab govitecan-hziy (Trodelvy) have demonstrated superior outcomes compared with standard chemotherapy drugs commonly used in patients, Foldi begins. These ADCs consistently outperform conventional chemotherapy in all evaluated outcomes, indicating a significant advancement in targeting chemotherapy more effectively, she explains, noting that these drugs deliver more targeted versions of traditional cytotoxic chemotherapy.

Given these findings, Foldi recommends incorporating ADCs in second-line and subsequent treatment settings across all three subtypes of metastatic breast cancer. For HER2-positive breast cancer, an overwhelming amount of data supports the use of T-DXd in the second-line setting, she continues. However, this treatment space was previously dominated by the use of ado-trastuzumab emtansine (Kadcyla; T-DM1) as the standard of care, Foldi explains. However, the question remains whether there is still a role for T-DM1 following the establishment of T-DXd in this setting.

This paradigm shift underscores the importance of utilizing more targeted chemotherapy approaches to improve patient outcomes in metastatic breast cancer treatment, Foldi expands, noting that this approach could potentially extend survival rates and improve the quality of life for patients with HER2-positive metastatic breast cancer. Therefore, integrating ADCs like T-DXd and sacituzumab govitecan into treatment regimens could significantly enhance the care provided to patients with metastatic HER2-positive breast cancer, she concludes.