Dr Bardia on Efficacy Data from the DESTINY-Breast06 Trial of T-DXd in HER2-Low/-Ultralow Metastatic Breast Cancer

“Interestingly, the outcomes were similar in the HER2-low and -ultralow [populations, which] speaks to the mechanism of action of this drug.”

Aditya Bardia, MD, MPH, FASCO, a professor in the Department of Medicine in the Division of Hematology/Oncology, as well as the director, of Translational Research Integration at the UCLA Health Jonsson Comprehensive Cancer Center, discussed key efficacy findings from the phase 3 DESTINY-Breast06 trial (NCT04494425) in patients with HER2-low and -ultralow metastatic breast cancer.

On January 27, 2025, the FDA approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of adult patients with unresectable or metastatic, hormone receptor–positive, HER2-low or -ultralow breast cancer who progressed on at least 1 endocrine therapy in the metastatic setting.

DESTINY-Breast06 was a global clinical trial designed to compare the efficacy of T-DXd vs physician’s choice of chemotherapy—either a taxane or capecitabine—in patients with hormone receptor–positive, HER2-negative (including HER2-low and HER2-ultralow) metastatic breast cancer who had not previously received chemotherapy in the metastatic setting and had progressed on endocrine-based therapy. The trial demonstrated a statistically and clinically significant improvement in progression-free survival (PFS) for patients treated with T-DXd compared with standard chemotherapy, according to Bardia. The median PFS was 13.2 months (95% CI, 12.0-15.2) in the T-DXd arm vs 8.1 months (95% CI, 7.0-9.0) in the chemotherapy arm. Notably, in patients previously treated with CDK4/6 inhibitors, T-DXd generated a median PFS exceeding 1 year. This outcome underscores the efficacy of T-DXd in this treatment-refractory population, Bardia explained.

Additionally, the objective response rate was substantially higher in the T-DXd group compared with the chemotherapy group, at 62.6% vs 34.4%, respectively. Outcomes were consistent across both the HER2-low and HER2-ultralow expression subgroups, suggesting that the therapeutic activity of T-DXd is not strictly dependent on higher levels of HER2 expression andhighlighting the antibody-drug conjugate’s unique mechanism of action, Bardia concluded.