Modi, ShaunJacot, WilliamYamashita, ToshinariSohn, JoohyukVidal, MariaTokunaga, ErikoTsurutani, JunjiUeno,Naoto T.Prat Aparicio, AleixChae, Yee SooLee, Keun SeokNiikura, NaokiPark, Yeon HeeXu, BingheWang, XiaojiaGil Gil, MiguelLi, WeiPierga, Jean YvesIm, Seock-AhMoore, Halle C.F.Rugo, Hope S.Yerushalmi, RinatZagouri, FloraGombos, AndreaKi, Sung BaeLiu, QiangLuo, TingSaura, CristinaSchmid, PeterSun,TaoGambhire, DhirajYung, LotusWang, YibinSingh, JasmeetVitazka, PatrikMeinhardt, GeroldHarbeck, NadiaCamero, David A.2023-04-262023-04-262022-07-070028-4793https://hdl.handle.net/2445/197309Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers.We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients.Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P?=?0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P?=?0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).Copyright © 2022 Massachusetts Medical Society.12 p.application/pdfeng(c) NEJM, 2022Càncer de mamaAnticossos monoclonalsBreast cancerMonoclonal antibodiesinfo:eu-repo/semantics/article2023-04-26info:eu-repo/semantics/openAccess931582635665782