Perez-Garcia, Jose ManuelVaz Batista, MartaCortez, PatriciaRuiz-Borrego, ManuelCejalvo, Juan Miguelde la Haba-Rodriguez, JuanGarrigos, LaiaRacca, FabricioServitja, SoniaBlanch, SalvadorGion, MariaNave, MonicaFernandez-Abad, MariaMartinez-Bueno, AlejandroLlombart-Cussac, AntonioSampayo-Cordero, MiguelMalfettone, AndreaCortes, JavierBraga, Sofia2023-05-032023-05-032023Pérez-García JM, Vaz Batista M, Cortez P, Ruiz-Borrego M, Cejalvo JM, de la Haba-Rodriguez J, et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial. Neuro Oncol. 2023 Jan 5;25(1):157-166http://hdl.handle.net/10668/19821Trastuzumab 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. 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. 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 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.enAttribution-NonCommercial 4.0 Internationalhttps://creativecommons.org/licenses/by-nc/4.0/HER2-positiveT-DXdAdvanced breast cancerBrain metastasesTrastuzumab deruxtecanHumansFemaleBreast neoplasmsQuality of lifeReceptor, ErbB-2Antibodies, monoclonal, humanizedTrastuzumabCamptothecinCentral nervous systemresearch article35639825open accessAnticuerpos monoclonales humanizadosCalidad de vidaCamptotecinaNeoplasias de la mamaReceptor ErbB-2Sistema nervioso central10.1093/neuonc/noac1441523-5866PMC9825345https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825345https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825345/pdf