Amol Akhade, Senior Consultant at Fortis Hospitals Mumbai, shared a post on LinkedIn:
“DESTINY-Breast11: Anthracyclines May Finally Be Retired?
Destiny Breast 11 abstract out at ESMO 2025
Study Design
Phase 3, open-label trial comparing:
- T-DXd-THP – Trastuzumab deruxtecan (T-DXd ×4) – THP (Taxane + H + P ×4)
- vs ddAC-THP – Standard dose-dense anthracycline + cyclophosphamide – THP
Primary endpoint: pCR (ypT0/Tis, ypN0)
Key secondary: Event-Free Survival (EFS), safety.
n = 641 (321 vs 320)
Key Results
- pCR: 67.3% vs 56.3% – Δ +11.2% (95% CI 4.0–18.3; p=0.003)
- EFS HR: 0.56 (95% CI 0.26–1.17) – early favorable trend (only 4.5% maturity)
- Grade ≥3 AE: 37.5% vs 55.8% LVEF dysfunction: 1.9% vs 9.0%
ILD/pneumonitis: 4.4% vs 5.1%
Serious AEs: 10.6% vs 20.2%
Interpretation Efficacy: T-DXd-THP achieves significantly higher pCR across HR+ and HR- subsets.
Safety: Remarkable reduction in cardiac toxicity (1.9% vs 9%) and fewer high-grade events overall.
ILD: 4–5%, largely low-grade and manageable, no surgical delays.
EFS: Promising HR 0.56, but needs longer follow-up before changing practice.
Critical View
The data clearly point to better efficacy and tolerability with an anthracycline-free ADC regimen.
But a few caveats remain:
pCR ≠ long-term survival – history has taught us to be cautious. EFS data immature (4.5% maturity); we must await the full analysis. Cost, logistics, and ILD monitoring could be limiting factors in LMIC practice.
Still, if future data confirm durable benefit, this could mark the end of anthracyclines in HER2+ early breast cancer — a long-awaited paradigm shift.
Takeaway
DESTINY-Breast11 positions T-DXd-THP as the first anthracycline-free ADC regimen to outperform ddAC-THP in efficacy and safety.
A step closer to precision-driven, less toxic neoadjuvant therapy.”
More posts featuring Amol Akhade.
