Dr Bardia on Findings From DESTINY-Breast06 in HER2-Low Breast Cancer

Aditya Bardia, MD, MPH, FASCO, professor, Department of Medicine, Division of Hematology/Oncology, director, Translational Research Integration, member, Signal Transduction and Therapeutics, UCLA Jonsson Comprehensive Cancer Center, discusses the quality of life (QOL) outcomes in the HER2-low and HER2-ultralow populations of patients with metastatic hormone receptor–positive breast cancer who were treated with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in the phase 3 DESTINY-Breast06 trial (NCT04494425).

The DESTINY-Breast06 trial included patients with both HER2-low and HER2-ultralow metastatic breast cancer and assessed the effects of T-DXd on QOL and survival, Bardia begins. T-DXd was associated with less deterioration in QOL and health-related QOL compared with standard chemotherapy, a crucial consideration for patients with metastatic breast cancer who need both extended survival and maintained QOL, he reports. Given that in this trial T-DXd was given in the post-endocrine therapy setting, these findings are particularly valuable, according to Bardia. Improved disease control with T-DXd was correlated with better QOL, as disease progression often worsens QOL, he adds. Notably, T-DXd was associated with sustained health-related QOL in several domains, although some patients experienced more nausea with T-DXd than with physician’s choice of chemotherapy, such as capecitabine, underscoring the importance of managing adverse effects (AEs), Bardia notes.

This positive study demonstrated a median progression-free survival (PFS) of 13.2 months with T-DXd, alongside a trend toward improved overall survival, he reports. Unlike previous studies, DESTINY-Breast06 enrolled both HER2-low and HER2-ultralow subgroups, he expands. Even within the HER2-ultralow subgroup, T-DXd generated superior outcomes over standard chemotherapy, showcasing the efficacy of the antibody-drug conjugate across patients with varied levels of HER2 expression, Bardia states. These findings emphasize the clinical value of T-DXd in this setting, offering effective disease control, improved PFS, and, in some patients, better QOL, as well as underscoring the need for AEmanagement to optimize treatment tolerance, he concludes.