This phase 3 trial showed that T-DXd-THP significantly improved the pathological complete response rate compared with ddAC-THP in high-risk HER2-positive early breast cancer, with a pCR of 67.3%. T-DXd-THP also demonstrated a better safety profile with fewer serious adverse events. The hazard ratio for event-free survival favored T-DXd-THP, suggesting improved outcomes for this combination.
Study
|
Randomised, open-label, multicentre, phase 3 trial [NCT05113251] |
| High-risk HER2-positive early breast cancer (≥cT3cN0 or cT0–4cN1–3) |
| T-DXd x8 (n=286) vs T-DXd x4 -> THP x4 (n=321) vs ddAC x4 -> THP x4 (n=320)
|
Efficacy
|
pCR: 43% vs 67.3% vs 56.3% (T-DXd vs. T-DXd-THP vs. ddAC-THP) |
| pCR significantly better in T-DXd-THP vs. ddAC-THP (p=0.003) |
| pCR significantly worse in T-DXd x8 vs. ddAC-THP (p=0.001) |
| EFS HR: 0.56 [0.26-1.17] T-DXd-THP vs ddAC-THP
|
Safety
|
Grade >=3 AE: 22.6% vs 37.5% vs 55.8% |
| Serious AE: 10.2% vs 10.6% vs 20.2% |
| Left-ventricular dysfunction: 0.7% vs 1.3% vs 6.1% |
| Treatment-related deaths: 0.3% vs 0.6%
|
Ann Oncol. Published online 2025
http://doi.org/10.1016/j.annonc.2025.10.019
Reviewed by Ulas D. Bayraktar, MD on Nov 17, 2025
