DESTINY-Breast05 — Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in Patients With High-Risk HER2-Positive Early Breast Cancer With Residual Invasive Disease After Neoadjuvant Therapy

Phase 3 · 2025 · Breast Cancer

Design

Randomized, open-label phase 3 trial of adjuvant trastuzumab deruxtecan (5.4 mg/kg IV q3w × 14 cycles) versus trastuzumab emtansine (T-DM1, 3.6 mg/kg IV q3w × 14 cycles).

Population

High-risk HER2-positive early breast cancer (n=1,635) with residual invasive disease in the breast or axillary nodes after neoadjuvant therapy.

Primary Endpoint

invasive disease-free survival (IDFS)

Key Result

3-year IDFS 92.4% vs 83.7% — a 53% reduction in the risk of invasive recurrence or death (HR 0.47, 95% CI 0.34–0.66; P<0.0001); benefit consistent across all subgroups. Overall survival immature at interim analysis.

Guideline Impact

Positions adjuvant T-DXd as the leading post-neoadjuvant option for high-risk HER2-positive residual disease