{"entity":{"id":"destiny-breast06","kind":"trial","name":"DESTINY-Breast06","aka":[],"tldr":"Moved Enhertu ahead of chemotherapy in hormone-positive breast cancer and extended it to 'ultralow' HER2.","summary":"DESTINY-Breast06, trial NCT04494425 sponsored by Daiichi Sankyo and AstraZeneca and published in the New England Journal of Medicine in 2024, moved trastuzumab deruxtecan ahead of chemotherapy in HR-positive, HER2-low breast cancer after endocrine therapy and extended it to HER2-ultralow tumours. It randomised 866 chemotherapy-naive patients to trastuzumab deruxtecan or chemotherapy, met its primary progression-free survival endpoint in HER2-low disease with a similar benefit in the ultralow group and a much higher response rate, and was approved in 2025. It replicates DESTINY-Breast04 in an earlier line, and whether any HER2 expression threshold matters at all is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT04494425","url":"https://clinicaltrials.gov/study/NCT04494425"}],"tags":[],"related":[],"cancers":["breast-hr-positive","her2-low-metastatic-breast-cancer","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":["trastuzumab-deruxtecan"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":["her2-low"],"trials":[],"people":["giuseppe-curigliano"],"bottlenecks":[],"keyPapers":["paper-destiny-breast06-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04494425","phase":"3","setting":"HR+ HER2-low/ultralow breast cancer after endocrine therapy, chemotherapy-naive: T-DXd vs chemotherapy","sponsor":"Daiichi Sankyo / AstraZeneca","result":"PFS HR 0.62.","started":"2020-07-24","startedType":"actual","yearReported":2024,"enrolled":866,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival, HER2-low (BICR)","primary":true,"unit":"months","arms":[{"name":"Trastuzumab deruxtecan","n":359,"value":13.2},{"name":"Chemotherapy (TPC)","n":354,"value":8.1}],"hr":0.62,"ci":[0.51,0.74],"p":"<0.0001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2407086"},{"endpoint":"Progression-free survival, ITT (HER2-low + ultralow)","unit":"months","arms":[{"name":"Trastuzumab deruxtecan","n":436,"value":13.2},{"name":"Chemotherapy (TPC)","n":430,"value":8.1}],"hr":0.63,"ci":[0.53,0.75],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2407086"},{"endpoint":"Objective response rate, HER2-low","unit":"%","arms":[{"name":"Trastuzumab deruxtecan","value":56.5},{"name":"Chemotherapy (TPC)","value":32.2}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2407086"}],"replication":"Replicates DESTINY-Breast04 in an earlier line and extends it to HER2-ultralow."},"route":"/trials/destiny-breast06/","neighbours":{"cancer":[{"id":"her2-low-metastatic-breast-cancer","kind":"cancer","name":"HER2-low and HER2-ultralow metastatic breast cancer","route":"/cancers/her2-low-metastatic-breast-cancer/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"drug":[{"id":"her2-testing-assays","kind":"drug","name":"HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)","route":"/drugs/her2-testing-assays/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"}],"term":[{"id":"her2-low","kind":"term","name":"HER2-low and HER2-ultralow","route":"/terms/her2-low/"}],"person":[{"id":"giuseppe-curigliano","kind":"person","name":"Giuseppe Curigliano","route":"/people/giuseppe-curigliano/"}],"paper":[{"id":"paper-destiny-breast06-nejm-2024","kind":"paper","name":"DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer","route":"/key-papers/paper-destiny-breast06-nejm-2024/"}],"pairing":[{"id":"her2-low-to-tdxd","kind":"pairing","name":"HER2-low scoring → T-DXd","route":"/pairings/her2-low-to-tdxd/"}],"idea":[{"id":"idea-ai-her2-low-scoring","kind":"idea","name":"AI quantification of HER2-low and HER2-ultralow","route":"/ideas/idea-ai-her2-low-scoring/"},{"id":"idea-tr2-her2-low-reference-materials","kind":"idea","name":"Calibrated reference slides so every lab scores HER2-low the same way","route":"/ideas/idea-tr2-her2-low-reference-materials/"},{"id":"idea-tr2-biomarker-negative-arms","kind":"idea","name":"Randomised trials to test whether biomarker-negative patients really do not benefit","route":"/ideas/idea-tr2-biomarker-negative-arms/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}],"roadmap":[{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"}]}}