# Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial

Source: https://onco.cc/key-papers/paper-destiny-breast12-nat-med-2024/  
OnCo record `paper-destiny-breast12-nat-med-2024` (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-Breast12 trial registered as NCT04739761, in Nature Medicine (2024), chosen as the most cited paper whose own text cites the registry id.

## Summary

Trastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2-positive (HER2 +) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2 + mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (n = 263) and no BMs (n = 241)) treated with one or more prior anti-HER2-based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (non-BMs cohort). Additional endpoints included central nervous system (CNS) PFS, ORR, time to second progression, CNS ORR (BMs cohort), incidence of new symptomatic CNS metastases (non-BMs cohort), time to progression, duration of response, overall survival and safety (both cohorts). No formal hypothesis testing was conducted for this single-arm, open-label study. In the BMs cohort, 12-month PFS was 61.6% (95% confidence interval (CI): 54.9-67.6), and 12-month CNS PFS was 58.9% (95% CI: 51.9-65.3). In the non-BMs cohort, ORR was 62.7% (95% CI: 56.5-68.8). Grade 3 or higher adverse events occurred in 51% (BMs cohort) and 49% (non-BMs cohort) of patients. Investigator-reported interstitial lung disease/pneumonitis occurred in 16% (grade ≥3: 3%) of patients with BMs and 13% (grade ≥3: 1%) of patients without BMs. These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated patients with HER2 + mBC irrespective of stable/active baseline BMs. ClinicalTrials.gov identifier: NCT04739761.

Indexed on Europe PMC as PubMed record 39271844 (DOI 10.1038/s41591-024-03261-7). Its abstract cites the registry id NCT04739761, 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: 2024
- DOI: 10.1038/s41591-024-03261-7
- Authors: Harbeck N, Ciruelos E, Jerusalem G, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT04739761 with the most citations, so it is the natural first reading for anyone following the DESTINY-Breast12 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

- Nat Med 2024: https://doi.org/10.1038/s41591-024-03261-7
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39271844/
- Europe PMC: https://europepmc.org/article/MED/39271844
- ClinicalTrials.gov NCT04739761: https://clinicaltrials.gov/study/NCT04739761

## Connected records

- trials: [DESTINY-Breast12](https://onco.cc/trials/destiny-breast12/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)

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