{"entity":{"id":"destiny-breast12","kind":"trial","name":"DESTINY-Breast12","aka":[],"tldr":"Enhertu shrank brain metastases in most patients, including those with untreated lesions, answering a question its earlier trials had excluded.","summary":"DESTINY-Breast12, trial NCT04739761 sponsored by AstraZeneca and Daiichi Sankyo and reported in 2024, was a phase 3b/4 single-arm study showing that trastuzumab deruxtecan shrinks brain metastases in most patients with HER2-positive metastatic breast cancer, including those with untreated lesions, answering a question its earlier trials had excluded. Among 504 patients, 263 with brain metastases, the intracranial objective response rate was high, higher still in active or untreated brain metastases, and most patients with brain disease were progression-free at twelve months. OnCo links it to trastuzumab deruxtecan, the HER2-positive brain metastases term, the idea of systemic-first management of brain metastases and the brain as a bottleneck. Without a randomised comparison, whether systemic therapy should replace radiotherapy first in selected patients remains open.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04739761","url":"https://clinicaltrials.gov/study/NCT04739761"}],"tags":[],"related":[],"cancers":["breast-her2-positive","secondary-brain-tumours","her2-positive-breast-brain-metastases"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":["trastuzumab-deruxtecan"],"companies":["astrazeneca","daiichi-sankyo"],"institutions":[],"pathways":[],"terms":["her2-brain-metastases"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-destiny-breast12-nat-med-2024"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04739761","phase":"3","setting":"HER2+ metastatic breast cancer with or without brain metastases: single-arm T-DXd","sponsor":"AstraZeneca / Daiichi Sankyo","result":"CNS ORR 71.7%; 12-month PFS 61.6% in brain-metastasis cohort.","started":"2021-06-22","startedType":"actual","yearReported":2024,"enrolled":506,"enrolledBasis":"registry","outcomes":[{"endpoint":"Intracranial objective response rate","primary":true,"unit":"%","arms":[{"name":"T-DXd (brain metastasis cohort)","n":263,"value":71.7}],"source":"https://www.nature.com/articles/s41591-024-03261-7"}],"replication":"Consistent with DEBBRAH and TUXEDO phase 2 studies of T-DXd in brain metastases."},"route":"/trials/destiny-breast12/","neighbours":{"cancer":[{"id":"secondary-brain-tumours","kind":"cancer","name":"Brain metastases (secondary brain tumours)","route":"/cancers/secondary-brain-tumours/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"her2-positive-breast-brain-metastases","kind":"cancer","name":"HER2-positive breast cancer with brain metastases","route":"/cancers/her2-positive-breast-brain-metastases/"}],"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":"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-brain-metastases","kind":"term","name":"HER2-positive brain metastases","route":"/terms/her2-brain-metastases/"}],"paper":[{"id":"paper-destiny-breast12-nat-med-2024","kind":"paper","name":"Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial","route":"/key-papers/paper-destiny-breast12-nat-med-2024/"}],"idea":[{"id":"idea-cns-first-adc-strategy","kind":"idea","name":"Systemic-first management of HER2-positive brain metastases","route":"/ideas/idea-cns-first-adc-strategy/"}],"bottleneck":[{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}]}}