# Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer

Source: https://onco.cc/key-papers/paper-destiny-breast05-n-engl-j-med-2026/  
OnCo record `paper-destiny-breast05-n-engl-j-med-2026` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the DESTINY-Breast05 trial registered as NCT04622319, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.

## Summary

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer and residual disease after neoadjuvant therapy are at high risk for recurrence.

Methods: In a phase 3, open-label, international, randomized trial, we investigated postneoadjuvant trastuzumab deruxtecan (T-DXd; 5.4 mg per kilogram of body weight) as compared with trastuzumab emtansine (T-DM1; 3.6 mg per kilogram), the current standard treatment, in patients with HER2-positive breast cancer with residual invasive disease and node-positive disease at surgery or inoperable disease at diagnosis. The primary end point was invasive disease-free survival, and the key secondary end point was disease-free survival (including survival free from noninvasive breast cancers and second primary nonbreast cancers). Other end points included overall survival, distant recurrence-free interval, brain metastasis-free interval, and safety.

Results: A total of 1635 patients were randomly assigned (in a 1:1 ratio) to receive T-DXd (818 patients) or T-DM1 (817 patients). At the data-cutoff date, the median duration of follow-up was approximately 30 months in each group. Invasive-disease events or deaths were reported in 51 patients (6.2%) in the T-DXd group and 102 patients (12.5%) in the T-DM1 group (hazard ratio, 0.47; 95% confidence interval [CI], 0.34 to 0.66; P<0.001); 3-year invasive disease-free survival was 92.4% and 83.7%, respectively. Invasive-disease events, noninvasive-disease events, or deaths were reported in 52 patients (6.4%) in the T-DXd group and 103 patients (12.6%) in the T-DM1 group (hazard ratio, 0.47; 95% CI, 0.34 to 0.66; P<0.001); 3-year disease-free survival was 92.3% and 83.5%, respectively. The most common adverse events were nausea (71.3% of patients), constipation (32.0%), decreased neutrophil count (31.6%), and vomiting (31.0%) with T-DXd and increased liver-enzyme levels (aspartate aminotransferase [50.2%] and alanine aminotransferase [45.3%]) and decreased platelet count (49.8%) with T-DM1. The incidence of adjudicated drug-related interstitial lung disease was higher with T-DXd than with T-DM1 (9.6% vs. 1.6%). Two patients with interstitial lung disease in the T-DXd group died.

Conclusions: In patients with high-risk, residual invasive HER2-positive breast cancer, postneoadjuvant T-DXd resulted in a significantly higher likelihood of invasive disease-free survival than T-DM1; toxic effects were mainly gastrointestinal and hematologic. An important identified risk of T-DXd is interstitial lung disease, which requires appropriate monitoring and management. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast05 ClinicalTrials.gov number, NCT04622319.).

Indexed on Europe PMC as PubMed record 41370739 (DOI 10.1056/nejmoa2514661). Its abstract cites the registry id NCT04622319, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: New England Journal of Medicine
- Year: 2026
- DOI: 10.1056/nejmoa2514661
- Authors: Loibl S, Park YH, Shao Z, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT04622319 with the most citations, so it is the natural first reading for anyone following the DESTINY-Breast05 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- N Engl J Med 2026: https://doi.org/10.1056/nejmoa2514661
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41370739/
- Europe PMC: https://europepmc.org/article/MED/41370739
- ClinicalTrials.gov NCT04622319: https://clinicaltrials.gov/study/NCT04622319

## Connected records

- trials: [DESTINY-Breast05](https://onco.cc/trials/destiny-breast05/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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