Trastuzumab Deruxtecan Provides Significant Clinical Benefit Over Trastuzumab Emtansine in HER2-Positive Early Breast Cancer
According to results from the phase 3 DESTINY-Breast05 trial, trastuzumab deruxtecan (T-DXd) significantly improved survival results compared to trastuzumab emtansine (T-DM1) among patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer.
These data were presented by Charles Geyer, MD, University of Pittsburgh, Pennsylvania, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
In this study, 1635 patients at high risk for recurrence following neoadjuvant treatment with a taxane-based chemotherapy and an anti-HER2 agent were randomized 1:1 to receive either 5.4 mg/kg of T-DXd (n = 818) or 3.6 mg/kg of T-DM1 (n = 817) once every 3 weeks for up to 14 cycles. The primary end point was invasive disease-free survival (iDFS). Key secondary end points included DFS and safety.
At analysis, the iDFS rate was 6.2% in the T-DXd arm and 12.5% in the T-DM1 arm (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.34 to 0.66; P <.0001). The DFS rates were 5.4% and 12.6%, respectively (HR 0.47; 95% CI, 0.34 to 0.66; P <.0001). Data presented also show a clinically meaningful improvement in brain metastasis-free interval with T-DXd vs T-DM1 (HR, 0.64; 95% CI, 0.35 to 1.17).
Grade ≥3 treatment-emergent adverse events occurred in 50.6% of patients in the T-DXd arm and 51.9% of patients in the T-DM1 arm and adjudicated drug-related interstitial lung disease occurred in 9.6% of patients and 1.6% of patients, respectively. Treatment-emergent events led to 3 deaths in the T-DXd arm and 5 deaths in the T-DM1 arm.
As Dr Geyer concluded, “T-DXd showed a statistically significant and clinically meaningful IDFS and DFS benefit vs T-DM1, extending its superiority to post-neoadjuvant residual disease in [patients] with [HER2-positive early breast cancer], and representing a potential new [standard of care].”
Source:
Geyer C, Park YH, Shao ZM, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): Interim analysis of DESTINY-Breast05. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA1
