# Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer

Source: https://onco.cc/key-papers/paper-destiny-breast09-n-engl-j-med-2026/  
OnCo record `paper-destiny-breast09-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-Breast09 trial registered as NCT04784715, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.

## Summary

Background: Trastuzumab deruxtecan has shown efficacy in patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer. The efficacy and safety of trastuzumab deruxtecan in patients with no previous therapy for HER2-positive advanced or metastatic breast cancer are unclear.

Methods: We conducted a phase 3 trial involving patients with HER2-positive advanced or metastatic breast cancer and no previous chemotherapy or HER2-directed therapy for metastatic disease. Patients were randomly assigned in a 1:1:1 ratio to receive trastuzumab deruxtecan plus pertuzumab; trastuzumab deruxtecan plus placebo; or a taxane, trastuzumab, and pertuzumab (THP). The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included objective response, duration of response, and safety.

Results: For this prespecified interim analysis, data for trastuzumab deruxtecan plus pertuzumab and for THP are reported; data for trastuzumab deruxtecan plus placebo remain blinded until the final analysis of progression-free survival. At the data-cutoff date (February 26, 2025), the median progression-free survival was 40.7 months with trastuzumab deruxtecan plus pertuzumab (383 patients) and 26.9 months with THP (387 patients) (hazard ratio for progression or death, 0.56; 95% confidence interval [CI], 0.44 to 0.71; P<0.00001 [P-value boundary for superiority, 0.00043]). The incidence of a confirmed response was 85.1% with trastuzumab deruxtecan plus pertuzumab and 78.6% with THP (complete responses in 15.1% and 8.5%, respectively), with a median duration of response of 39.2 months and 26.4 months. Safety was consistent with the known profiles of the individual treatments. The incidence of grade 3 or higher adverse events was 63.5% with trastuzumab deruxtecan plus pertuzumab and 62.3% with THP; the most common were neutropenia, hypokalemia, and anemia with trastuzumab deruxtecan plus pertuzumab and neutropenia, leukopenia, and diarrhea with THP. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.1% of patients receiving trastuzumab deruxtecan plus pertuzumab (grade 1 or 2 in 44 patients and grade 5 [death] in 2 patients) and in 1.0% of those receiving THP (all grade 1 or 2).

Conclusions: Trastuzumab deruxtecan plus pertuzumab led to a significantly lower risk of progression or death than THP when used as first-line treatment for HER2-positive advanced or metastatic breast cancer, with no new safety signals. (Funded by AstraZeneca and Daiichi Sankyo; DESTINY-Breast09 ClinicalTrials.gov number, NCT04784715.).

Indexed on Europe PMC as PubMed record 41160818 (DOI 10.1056/nejmoa2508668). Its abstract cites the registry id NCT04784715, 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/nejmoa2508668
- Authors: Tolaney SM, Jiang Z, Zhang Q, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT04784715 with the most citations, so it is the natural first reading for anyone following the DESTINY-Breast09 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/nejmoa2508668
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41160818/
- Europe PMC: https://europepmc.org/article/MED/41160818
- ClinicalTrials.gov NCT04784715: https://clinicaltrials.gov/study/NCT04784715

## Connected records

- trials: [DESTINY-Breast09](https://onco.cc/trials/destiny-breast09/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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