IN the first presidential symposium of ESMO 2025, the results from the phase 3 DESTINY-Breast11 trial were presented. It highlights the potential of the neoadjuvant, anthracycline-free T-DXd-THP regimen to redefine treatment for patients with high-risk HER2-positive early breast cancer (HER2+ eBC).
Study Overview and Design
The multicentre, open-label study evaluated trastuzumab deruxtecan (T-DXd) in combination with trastuzumab, pertuzumab, and a taxane (THP), compared against the standard dose-dense doxorubicin plus cyclophosphamide (ddAC) followed by THP. Eligible participants included adults with untreated, high-risk HER2+ eBC—tumours ≥T3, node-positive (N1–3), or inflammatory disease. The primary objective was to see how many patients had no remaining invasive cancer in their breast or lymph nodes at surgery (called pathologic complete response, or pCR), and secondary endpoints included event-free survival (EFS) and safety.
Efficacy Advantage with Higher pCR and Early EFS Trend
As of March 2025, 640 patients were randomly assigned to receive either T-DXd followed by other drugs (THP treatment) or the standard chemotherapy regimen (ddAC-THP). The pathologic complete response rates, or pCR, were 67.3% for the T-DXd-THP arm versus 56.3% for ddAC-THP (Δ11.2%, 95% CI: 4.0–18.3; P=0.003). Improvements were consistent across hormone receptor–positive and hormone receptor–negative subgroups.
An early favourable event-free survival (EFS) trend was observed in the T-DXd-THP arm (hazard ratio 0.56; 95% CI: 0.26–1.17), suggesting possible long-term benefit with T-DXd therapy in the neoadjuvant setting.
Reduced Toxicity and Enhanced Safety
The T-DXd-THP regimen demonstrated a safer toxicity profile, with fewer grade ≥3 adverse events (37.5% vs 55.8%) and a markedly lower rate of left ventricular dysfunction (1.9% vs 9.0%). Cases of drug-related pneumonitis/interstitial lung disease (ILD) were infrequent and comparable across arms. Notably, no adverse event prevented surgical intervention.
A New Standard Emerging in Breast Cancer Care
Findings from DESTINY-Breast11, presented at ESMO 2025, reinforce neoadjuvant T-DXd-THP as a potential new standard for high-risk HER2-positive early breast cancer, delivering superior efficacy with reduced toxicity compared with traditional anthracycline-based regimens.
Reference
Harbeck N et al. DESTINY-Breast11: Neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC). Abstract 291O. ESMO; 17-21 October, Berlin, Germany.
