# Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): a randomised, open-label, multicentre, phase III trial

Source: https://onco.cc/key-papers/paper-trastuzumab-deruxtecan-breast-hr-positive-ann-oncol-2026/  
OnCo record `paper-trastuzumab-deruxtecan-breast-hr-positive-ann-oncol-2026` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Phase 2 or 3 results paper on Trastuzumab deruxtecan in HR-positive / HER2-negative breast cancer, in Annals of Oncology (2026), one of the most cited Europe PMC records with Trastuzumab deruxtecan in its title.

## Summary

Background: Neoadjuvant standard-of-care for HER2-positive early-stage breast cancer is trastuzumab + pertuzumab with polychemotherapy; however, existing regimens have high toxicity burdens and suboptimal outcomes. DESTINY-Breast11 assessed efficacy and safety of neoadjuvant trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel + trastuzumab + pertuzumab (THP) versus dose-dense doxorubicin + cyclophosphamide (ddAC) followed by THP for high-risk (≥cT3cN0 or cT0-4cN1-3) HER2-positive disease.

Patients and methods: This open-label, phase III trial (147 sites, 18 countries) randomised adults 1: 1: 1 to T-DXd (×8 cycles), T-DXd-THP (4 + 4 cycles), or ddAC-THP (4 + 4 cycles). T-DXd-alone arm enrolment closed early following the Independent Data Monitoring Committee recommendation. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0; intent-to-treat population). Secondary endpoints included event-free survival (EFS; intent-to-treat population) and safety (safety analysis set).

Results: Between 25 October 2021 and 12 March 2025, 286 (T-DXd), 321 (T-DXd-THP), and 320 (ddAC-THP) female patients were randomised. pCR rates were 43.0% (T-DXd, n = 123), 67.3% (T-DXd-THP, n = 216), and 56.3% (ddAC-THP, n = 180). T-DXd-THP versus ddAC-THP absolute pCR rate difference was 11.2% [95% confidence interval (CI), 4.0% to 18.3%, P = 0.003], with benefit in hormone receptor (HR)-positive [61.4% (n/N = 145/236) versus 52.3% (n/N = 123/235); difference in pCR (ΔpCR) 9.1% (95% CI 0.2% to 17.9%)] and HR-negative [83.1% (n/N = 69/83) versus 67.1% (n/N = 57/85); ΔpCR 16.1% (95% CI 3.0% to 28.8%)] subgroups. Median EFS (T-DXd-THP versus ddAC-THP, maturity 4.5%) hazard ratio was 0.56 (95% CI 0.26 to 1.17). Grade ≥3 adverse events (AE; T-DXd, 22.6% (n = 64); T-DXd-THP, 37.5% (n = 120); ddAC-THP, 55.8% (n = 174)], serious AE [T-DXd, 10.2% (n = 29); T-DXd-THP, 10.6% (n = 34); ddAC-THP, 20.2% (n = 63)], and all-grade left-ventricular dysfunction [T-DXd, 0.7% (n = 2); T-DXd-THP, 1.3% (n = 4); ddAC-THP, 6.1% (n = 19)] rates were lower for T-DXd and T-DXd-THP than ddAC-THP. All-grade adjudicated drug-related interstitial lung disease/pneumonitis rates were low and similar across arms [T-DXd, 4.9% (n = 14); T-DXd-THP, 4.4% (n = 14); ddAC-THP, 5.1% (n = 16)]. Three treatment-related deaths occurred [T-DXd-THP, 0.3% (n = 1); ddAC-THP, 0.6% (n = 2)].

Conclusions: Neoadjuvant T-DXd-THP demonstrated statistically significant and clinically meaningful pCR benefit and improved safety versus ddAC-THP.

Indexed on Europe PMC as PubMed record 41130363 (DOI 10.1016/j.annonc.2025.10.019). Its title names Trastuzumab deruxtecan and its text names HR-positive / HER2-negative breast cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea "AI quantification of HER2-low and HER2-ultralow" and no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Annals of Oncology
- Year: 2026
- DOI: 10.1016/j.annonc.2025.10.019
- Authors: Harbeck N, Modi S, Pusztai L, et al.
- What it means: One of the most cited trial reports Europe PMC returns for Trastuzumab deruxtecan in HR-positive / HER2-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Caveats: Matched by Trastuzumab deruxtecan in the title and HR-positive / HER2-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper.

## Sources

- Ann Oncol 2026: https://doi.org/10.1016/j.annonc.2025.10.019
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41130363/
- Europe PMC: https://europepmc.org/article/MED/41130363

## Connected records

- journals: [Annals of Oncology](https://onco.cc/journals/annals-of-oncology/)
- ideas: [AI quantification of HER2-low and HER2-ultralow](https://onco.cc/ideas/idea-ai-her2-low-scoring/)

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