# Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial

Source: https://onco.cc/key-papers/paper-destiny-breast04-nat-med-2025-update/  
OnCo record `paper-destiny-breast04-nat-med-2025-update` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Later report from the DESTINY-Breast04 trial registered as NCT03734029, in Nature Medicine (2025); its title describes an updated or longer-term analysis.

## Summary

In DESTINY-Breast04 ( NCT03734029), trastuzumab deruxtecan (T-DXd) significantly improved overall survival (OS) and progression-free survival compared with treatment of physician's choice of chemotherapy (TPC) for patients with human epidermal growth factor receptor 2-low (HER2-low) (immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization-negative) metastatic breast cancer. After an extended median follow-up of 32.0 months, median OS in the overall cohort was 22.9 months for T-DXd and 16.8 months for TPC (hazard ratio 0.69; 95% confidence interval 0.55-0.86). For the hormone receptor-positive cohort, median OS was 23.9 and 17.6 months for T-DXd and TPC, respectively (hazard ratio 0.69; 95% confidence interval 0.55-0.87). Median OS also favored T-DXd in exploratory analyses of hormone receptor-negative, estrogen receptor IHC 1%-10% and estrogen receptor IHC >10% cohorts. The overall safety profile of T-DXd was acceptable and generally manageable. Results confirm T-DXd as standard of care after prior chemotherapy in patients with HER2-low metastatic breast cancer. ClinicalTrials.gov identifier: NCT03734029.

Indexed on Europe PMC as PubMed record 41062831 (DOI 10.1038/s41591-025-03981-4). Its abstract cites the registry id NCT03734029, 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: Nature Medicine
- Year: 2025
- DOI: 10.1038/s41591-025-03981-4
- Authors: Modi S, Jacot W, Iwata H, et al.
- What it means: A second publication from the DESTINY-Breast04 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; 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.; Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper.

## Sources

- Nat Med 2025: https://doi.org/10.1038/s41591-025-03981-4
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41062831/
- Europe PMC: https://europepmc.org/article/MED/41062831
- ClinicalTrials.gov NCT03734029: https://clinicaltrials.gov/study/NCT03734029

## Connected records

- trials: [DESTINY-Breast04](https://onco.cc/trials/destiny-breast04/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)

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