Dr Foldi on the Evolving Role of T-DXd 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, UPMC Hillman Cancer Center, discusses the evolving role of fam-trastuzumab deruxtecan-nxki (Enthertu; T-DXd) in the treatment of metastatic HER2-positive breast cancer.

Within the HER2-positive setting there is also the HER2-low setting, which can make treatment navigation even more complicated, Foldi begins. In HER2-positive disease, T-DXd is the current standard of care (SOC) in the second-line setting following progression on standard, first-line pertuzumab (Verzenio), trastuzumab (Herceptin), and docetaxel, Foldi begins. In the phase 3 DESTINY-Breast03 trial (NCT03529110), T-DXd demonstrated a significant progression-free survival (PFS) and overall survival (OS) benefit over the prior SOC, ado-trastuzumab emtansine (Kadcyla; T-DM1), and was accordingly established as the preferred second-line treatment option, Foldi reports.

Prior trials such as the phase 2 DESTINY-Breast01 (NCT03248492) and phase 3 DESTINY-Breast02 (NCT03523585) studies had already positioned T-DXd as an effective treatment in later lines of therapy, demonstrating its efficacy and tolerability in more advanced stages of the disease, Foldi explains. IN DESTINY-Breast01, T-DXd generated superior response rates in a heavily pretreated patient population; T-DXd also produced superior efficacy vs physician's choice of chemotherapy in the third-line and beyond in the DESTINY-Breast02 trial, she says. Foldi emphasizes that the DESTINY-Breast03 trial expanded on these findings by confirming T-DXd's role in earlier lines of therapy.

Ongoing research is exploring the potential use of T-DXd in earlier treatment lines, including the first-line setting, Foldi continues. An ongoing trial will compare T-DXd with taxane-based chemotherapy and HER2-targeting antibody combinations. This approach reflects a broader effort to optimize treatment strategies and leverage the benefits of T-DXd across different stages of HER2-positive breast cancer, Foldi explains.

Overall, T-DXd's emergence represents a significant advancement in the therapeutic landscape, improving outcomes for patients with HER2-positive breast cancer, especially those facing disease progression after initial therapies.