{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T01:27:58Z","timestamp":1794014878826,"version":"4.8.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002973","name":"Daiichi-Sankyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002973","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report the final PFS and OS results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and Methods<\/jats:title>\n                  <jats:p>TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analyzed in the per-protocol population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At 26.5 months median follow-up, median PFS was 21 months (95% CI: 13.3\u2013n.r.) and median OS was not reached (95% CI: 22.2\u2013n.r.). With longer follow-ups, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of antibody-drug-conjugates as systemic therapy for active BM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae123","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T17:17:17Z","timestamp":1720113437000},"page":"2305-2315","source":"Crossref","is-referenced-by-count":54,"title":["Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4384-6917","authenticated-orcid":false,"given":"Rupert","family":"Bartsch","sequence":"first","affiliation":[{"name":"Department of Medicine I, Division of Oncology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Sophie","family":"Berghoff","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Oncology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Furtner","sequence":"additional","affiliation":[{"name":"Research Center for Medical Image Analysis and Artificial Intelligence (MIAAI), Faculty of Medicine and Dentistry, Danube Private University , Krems ,","place":["Austria"]},{"name":"Department of Radiology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Marhold","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Oncology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth Sophie","family":"Bergen","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Oncology, Medical University of Vienna , Vienna 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