biostudies-literatureHarbeck NHealth Research Board3717-3727https://www.ebi.ac.uk/biostudies/studies/S-EPMC11645283biostudies-literatureUnknown30(12)Trastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2-positive (HER2⁺) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2⁺ mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (n = 263) and no BMs (n = 241)) treated with one or more prior anti-HER2-based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria iNature medicineTrastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial.PMC11645283CTIC-2021-002Connolly RMClay TDe Laurentiis MTsurutani JHarbeck NJerusalem GBraun MEngebraten OFotia VMuller VRossi LHuovinen RCaruso MBrix EGuarneri VNiikura NDe Cuypere ESousa ARUntch MMurray NMcCarthy NTsugawa KPilskog MTesch HPrahladan MBerardi RMarti MPLMcCartney ADuchnowska RCastan JCHall PYeo BBiganzoli LAnders CBianchini GScotto NKillander FTanner MGrischke EMDel Prado PMZaman KRonlev JMattson JViale GKlint LGombos AMarme Fde Boer MTomioka NSætersdal AWildiers HCollignon JReinisch MSimoes JLosada MJVKurzeder Cvan Mackelenbergh MGregori JGKuptsova-Clarkson NAebi SManich CSBorrego MRGonzalez CHEscriva-de-Romani SJassem JVerma SRadecka BJerzak KPark-Simon TWBridge HLopez RLNowecki ZGion MChia SCiruelos EHoutsma DSanchez CRHiggins MJDESTINY-Breast12 study groupFasching PYamashita TMaraldo MTio JWimberger PMcCaffrey JWysocki PBaron-Hay SCardoso FSchiza ABartsch RLin NUFlores EGfalseTrastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial.Trastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2-positive (HER2⁺) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2⁺ mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (n = 263) and no BMs (n = 241)) treated with one or more prior anti-HER2-based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria i2024-01-01T00:00:00Z2024 Dec2026-06-01T07:15:14.615Z2025-04-04T01:54:51.384ZS-EPMC116452833927184410.1038/s41591-024-03261-7