机构：[1]Memorial Sloan Kettering Cancer Center, New York[2]Institut du Cancer de Montpellier, Université Montpellier, INSERM Unité 1194, Montpellier,France[3]Institut Curie, Université Paris Cité, Paris,France[4]Kanagawa Cancer Center, Yokohama,Japan[5]Kyushu Cancer Center, National Hospital Organization, Fukuoka,Japan[6]Showa University Hospital, Tokyo,Japan[7]Tokai University School of Medicine, Isehara-shi,Japan[8]Yonsei Cancer Center, Yonsei University Health System,South Korea[9]Samsung Medical Center,South Korea[10]Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University,South Korea[11]Asan Medical Center, University of Ulsan College of Medicine,South Korea[12]Seoul, Kyungpook National University Chilgok Hospital, Daegu,South Korea[13]National Cancer Center, Goyang-si,South Korea[14]Department of Medical Oncology, Hospital Clínic de Barcelona,Barcelona[15]Translational Genomics and Targeted Therapies in Solid Tumors, Institut d’Investigacions Biomèdiques August Pi i Sunyer,Barcelona[16]Department of Medicine, University of Barcelona,Barcelona[17]Breast Cancer Unit, Institute of Oncology (IOB)–Quirón Salud,Barcelona[18]Institut Catala d’Oncologia l’Hospitalet–Hospital Duran i Reynals,Barcelona[19]Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology,Barcelona[20]University of Texas M.D. Anderson Cancer Center, Houston[21]Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing,China[22]Zhejiang Cancer Hospital, Hangzhou,China浙江省肿瘤医院[23]First Hospital of Jilin University, Changchun,China[24]Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou,China中山大学附属第二医院[25]West China Hospital, Sichuan University, Chengdu,China四川大学华西医院[26]Liaoning Cancer Hospital and Institute, Shenyang,China[27]Cleveland Clinic Foundation, Cleveland[28]University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco[29]Rabin Medical Center, Petah Tikva, Tel Aviv University, Tel Aviv, Israel[30]Alexandra Regional General Hospital, Athens[31]Institut Jules Bordet, Brussels[32]Queen Mary University of London, London,United Kingdom[33]Edinburgh Cancer Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh,United Kingdom[34]Daiichi Sankyo, Basking Ridge, NJ[35]Breast Center, Department of Obstetrics and Gynecology, and Comprehensive Cancer Center Munich, Ludwig Maximilian University Hospital, Munich, Germany
BACKGROUND Among 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. METHODS 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. RESULTS 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. CONCLUSIONS 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, .)
第一作者机构：[1]Memorial Sloan Kettering Cancer Center, New York[*1]Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065
通讯作者：
通讯机构：[1]Memorial Sloan Kettering Cancer Center, New York[*1]Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065
推荐引用方式(GB/T 7714)：
Modi Shanu,Jacot William,Yamashita Toshinari,et al.Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer[J].NEW ENGLAND JOURNAL OF MEDICINE.2022,387(1):9-20.doi:10.1056/NEJMoa2203690.
APA：
Modi, Shanu,Jacot, William,Yamashita, Toshinari,Sohn, Joohyuk,Vidal, Maria...&Cameron, David A..(2022).Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer.NEW ENGLAND JOURNAL OF MEDICINE,387,(1)
MLA：
Modi, Shanu,et al."Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer".NEW ENGLAND JOURNAL OF MEDICINE 387..1(2022):9-20
医学