{"entity":{"id":"paper-destiny-breast04-nat-med-2025-update","kind":"paper","name":"Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial","aka":[],"tldr":"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.\n\nIndexed 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.","asOf":"2026-09-22","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-025-03981-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41062831/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41062831"},{"label":"ClinicalTrials.gov NCT03734029","url":"https://clinicaltrials.gov/study/NCT03734029"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-breast04"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-025-03981-4","pmid":"41062831","authors":"Modi S, Jacot W, Iwata H, et al.","paperType":"rct","findings":[],"whatItMeans":"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."]},"route":"/key-papers/paper-destiny-breast04-nat-med-2025-update/","neighbours":{"trial":[{"id":"destiny-breast04","kind":"trial","name":"DESTINY-Breast04","route":"/trials/destiny-breast04/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}]}}