Dr Yuan on T-DXd in First-Line HER2+ Advanced/Metastatic Breast Cancer

“[With T-DXd,] most patients will enjoy a very durable, progression-free period without any intensive chemotherapy or chemotoxicity.”

Yuan Yuan, MD, PhD, the director of Breast Medical Oncology Medicine, the medical director of the Breast Oncology Disease Research Group, and a professor at Cedars-Sinai Medical Cente;, as well as a health sciences clinical professor at the University of California, Los Angeles, discussed findings from the phase 3 DESTINY-Breast09 trial (NCT04784715) of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta) for the frontline treatment of patients with HER2-positive advanced/metastatic breast cancer.

DESTINY-Breast09 compared treatment with T-DXd plus pertuzumab with the current frontline standard of care of a taxane plus trastuzumab (Herceptin) and pertuzumab (THP), Yuan began. Prior to DESTINY-Breast 09, T-DXd monotherapy was evaluated in patients who experienced disease progression following treatment with ado-trastuzumab emtansine (T-DM1; Kadcyla) in the phase 3 DESTINY-Breast02 study (NCT03523585) and was compared with T-DM1 in patients who previously received trastuzumab and a taxane in the phase 3 DESTINY-Breast03 trial (NCT03529110), she added.

During the 2025 ASCO Annual Meeting, updated data from DESTINY-Breast09 were demonstrated that patients who received T-DXd (n = 383) achieved a median progression-free survival (PFS) of 40.7 months (95% CI, 36.5-not calculable [NC]) compared with 26.9 months (95% CI, 21.8-NC) among patients who received THP (n = 387; HR, 0.56; 95% CI, 0.44-0.71; P < .00001). The 24-month PFS rates were 70.1% (95% CI, 64.8%-74.8%) and 52.1% (95% CI, 46.4%-57.5%), respectively.

In terms of safety, treatment with T-DXd can lead to gastrointestinal toxicities, such as nausea, as well as hair loss, Yuan said. Additionally, the continuous dosing of the agent can lead to interstitial lung disease (ILD), she added; any-grade occurred in 12.1% of patients who received T-DXd (n = 381) compared with 1.0% of patients treated with THP (n = 382).