{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:07:29Z","timestamp":1790856449557,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022274","name":"Daiichi Sankyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Trastuzumab deruxtecan (T-DXd) has shown durable antitumor activity in pretreated patients with HER2-positive advanced breast cancer (ABC), but its efficacy has not yet been evaluated in patients with active brain metastases (BMs). DEBBRAH aims to assess T-DXd in patients with HER2-positive or HER2-low ABC and central nervous system involvement.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This ongoing, five-cohort, phase II study (NCT04420598) enrolled patients with pretreated HER2-positive or HER2-low ABC with stable, untreated, or progressing BMs, and\/or leptomeningeal carcinomatosis. Here, we report findings from HER2-positive ABC patients with non-progressing BMs after local therapy (n = 8; cohort 1), asymptomatic untreated BMs (n = 4; cohort 2), or progressing BMs after local therapy (n = 9; cohort 3). Patients received 5.4 mg\/kg T-DXd intravenously once every 21 days. The primary endpoint was 16-week progression-free survival (PFS) for cohort 1 and intracranial objective response rate (ORR-IC) for cohorts 2 and 3.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>As of October 20, 2021, 21 patients received T-DXd. In cohort 1, 16-week PFS rate was 87.5% (95%CI, 47.3-99.7; P &amp;lt; .001). ORR-IC was 50.0% (95%CI, 6.7-93.2) in cohort 2 and 44.4% (95%CI, 13.7-78.8; P &amp;lt; .001) in cohort 3. Overall, the ORR-IC in patients with active BMs was 46.2% (95%CI, 19.2-74.9). Among patients with measurable intracranial or extracranial lesions at baseline, the ORR was 66.7% (12 out of 18 patients; 95%CI, 41.0-86.7), 80.0% (95%CI, 28.4-99.5) in cohort 1, 50.0% (95%CI, 6.7-93.2) in cohort 2, and 66.7% (95%CI, 29.9-92.5) in cohort 3. All responders had partial responses. The most common adverse events included fatigue (52.4%; 4.8% grade \u22653), nausea (42.9%; 0% grade \u22653), neutropenia (28.6%; 19% grade \u22653), and constipation (28.6%; 0% grade \u22653). Two (9.5%) patients suffered grade 1 interstitial lung disease\/pneumonitis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>T-DXd showed intracranial activity with manageable toxicity and maintained the quality of life in pretreated HER2-positive ABC patients with stable, untreated, or progressing BMs. Further studies are needed to validate these results in larger cohorts.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noac144","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T19:31:13Z","timestamp":1654025473000},"page":"157-166","source":"Crossref","is-referenced-by-count":222,"title":["Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial"],"prefix":"10.1093","volume":"25","author":[{"given":"Jos\u00e9 Manuel","family":"P\u00e9rez-Garc\u00eda","sequence":"first","affiliation":[{"name":"International Breast Cancer Center (IBCC), Quironsalud Group , Barcelona , Spain"},{"name":"Medica Scientia Innovation Research (MEDSIR) , Barcelona , Spain"},{"name":"Medica Scientia Innovation Research (MEDSIR) , Ridgewood, New Jersey , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Vaz Batista","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MEDSIR) , Barcelona , Spain"},{"name":"Medica Scientia Innovation Research (MEDSIR) , Ridgewood, New Jersey , USA"},{"name":"Hospital Professor Doutor Fernando Fonseca EPE , Lisbon , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Cortez","sequence":"additional","affiliation":[{"name":"IOB Institute of Oncology, Hospital Ruber Internacional, Quiron Group , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Ruiz-Borrego","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Roc\u00edo , Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Miguel","family":"Cejalvo","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico Universitario de Valencia, Biomedical Research Institute INCLIVA , Valencia , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"de la Haba-Rodriguez","sequence":"additional","affiliation":[{"name":"Instituto Maimonides de Investigacion Biomedica, Hospital Reina Sofia, Universidad de C\u00f3rdoba , C\u00f3rdoba , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Garrig\u00f3s","sequence":"additional","affiliation":[{"name":"International Breast Cancer Center (IBCC), Quironsalud Group , Barcelona , Spain"},{"name":"Hospital Universitari Dexeus , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabricio","family":"Racca","sequence":"additional","affiliation":[{"name":"IOB Institute of Oncology, Quiron Group , Madrid and Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Servitja","sequence":"additional","affiliation":[{"name":"Hospital del Mar , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Blanch","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MEDSIR) , Barcelona , Spain"},{"name":"Medica Scientia Innovation Research (MEDSIR) , Ridgewood, New Jersey , USA"},{"name":"Hospital Professor Doutor Fernando Fonseca EPE , Lisbon , Portugal"},{"name":"Fundaci\u00f3n Instituto Valenciano de Oncolog\u00eda , Valencia , 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Spain"},{"name":"Medica Scientia Innovation Research (MEDSIR) , Ridgewood, New Jersey , USA"},{"name":"Hospital Arnau de Vilanova, FISABIO , Valencia , Spain"},{"name":"Universidad Cat\u00f3lica de Valencia , Valencia , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Sampayo-Cordero","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MEDSIR) , Barcelona , Spain"},{"name":"Medica Scientia Innovation Research (MEDSIR) , Ridgewood, New Jersey , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Malfettone","sequence":"additional","affiliation":[{"name":"Medica Scientia Innovation Research (MEDSIR) , Barcelona , Spain"},{"name":"Medica Scientia Innovation Research (MEDSIR) , Ridgewood, New Jersey , 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Portugal"},{"name":"Fundaci\u00f3n Instituto Valenciano de Oncolog\u00eda , Valencia , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"issue":"12","key":"2023010802382083600_CIT0001","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.3390\/cancers13122927","article-title":"Brain metastases in HER2-positive breast cancer: current and novel treatment strategies","volume":"13","author":"Garcia-Alvarez","year":"2021","journal-title":"Cancers."},{"issue":"5","key":"2023010802382083600_CIT0002","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.3390\/cancers13051078","article-title":"Breast cancer brain metastasis\u2014overview of disease state, treatment options and future 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