Phase III study of dulanermin (recombinant human tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand) combined with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer
机构：[1]Department of Medical Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzong Clinical College, Fujian Medical University, Fuzhou, China[2]Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University affiliated Cancer Hospital, No.42 Baiziting, Xuanwu District, Nanjing, Jiangsu, 210009, China[3]Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China[4]Department of Medical Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China[5]Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China[6]Department of Chemotherapy, Qilu Hospital of Shandong University, Jinan, Shandong, China[7]Department of Medical Oncology, Fujian Provincial Cancer Hospital, The Teaching Hospital of Fujian Medical University, The Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China[8]Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China[9]Department of internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, China[10]Department of Radiation andMedical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China[11]Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China四川省人民医院[12]Department of Oncology, Jiangsu Proving Hospital, The First Affiliated Hospital of NanjingMedical University, Nanjing, Jiangsu, China[13]Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China[14]Department of Oncology, Renji Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China[15]Department of Medical Oncology, Zhejiang Cancer Hospital, Zhejiang, Hangzhou, China[16]Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China[17]Department of Respiratory and Critical Care Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, China[18]Department of Respiratory Medicine, Shanghai East Hospital, Tongji University, Shanghai, China[19]Department of Medical Oncology, Hunan Cancer Hospital, Changsha, Hunan, China[20]Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China[21]Department of Respiratory Medicine, Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu, China[22]Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China[23]Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China[24]Department of Medical Oncology, Changzheng Hospital, Shanghai, China[25]Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China[26]Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China[27]Department of Respiratory Medicine, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China[28]Department of Respiratory, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[29]Department of Respiratory Medicine, Changhai Hospital, The Second Military Medical University, Shanghai, China[30]Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
Background Dulanermin is a recombinant soluble human Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that activates apoptotic pathways by binding to proapoptotic death receptor (DR) 4 and DR5. The purpose of this study was to evaluate the efficacy and safety of dulanermin combined with vinorelbine and cisplatin (NP) as the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). Experimental design Patients were randomly assigned to receive NP chemotherapy (vinorelbine 25 mg/m(2) on days 1 and 8 and cisplatin 30 mg/m(2) on days 2 to 4) for up to six cycles plus dulanermin (75 mu g/kg on days 1 to 14) or placebo every three weeks until disease progression, intolerable toxicity, or withdrawal of consent. The primary end point was progression-free survival (PFS), and the secondary end points included objective response rate (ORR), overall survival (OS), and safety evaluation. Results Between October 2009 and June 2012, 452 untreated patients with stage IIIB to IV NSCLC were randomly assigned to receive dulanermin plus NP (n = 342) and placebo plus NP (n = 110). Median PFS was 6.4 months in the dulanermin arm versus 3.5 months in the placebo arm (hazard ratio (HR), 0.4034; 95% CI, 0.3181 to 0.5117, p < 0.0001). ORR was 46.78% in the dulanermin arm versus 30.00% in the placebo arm (p = 0.0019). Median OS was 14.6 months in the dulanermin arm versus 13.9 months in the placebo arm (HR, 0.94; 95% CI, 0.74 to 1.21, p = 0.64). The most common grade ae<yen> 3 adverse events (AEs) were oligochromemia, leukopenia, neutropenia, and oligocythemia. Overall incidence of AEs, grade ae<yen> 3 AEs, and serious AEs were similar across the two arms. Conclusion Addition of dulanermin to the NP regimen significantly improved PFS and ORR. However, our results showed that the combination of dulanermin with chemotherapy had a synergic activity and favorable toxic profile in the treatment of patients with advanced NSCLC.
基金：
The work was also funded by Shanghai Biomedical Technology
fund (grant number 08431901100), National Innovation Fund (grant
number 10C26213100701), and National Science and Technology
Major Project fund (grant number 2010ZX09401-301).
第一作者机构：[1]Department of Medical Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzong Clinical College, Fujian Medical University, Fuzhou, China
共同第一作者：
通讯作者：
通讯机构：[2]Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University affiliated Cancer Hospital, No.42 Baiziting, Xuanwu District, Nanjing, Jiangsu, 210009, China
推荐引用方式(GB/T 7714)：
Xuenong Ouyang,Meiqi Shi,Fangwei Jie,et al.Phase III study of dulanermin (recombinant human tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand) combined with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer[J].INVESTIGATIONAL NEW DRUGS.2018,36(2):315-322.doi:10.1007/s10637-017-0536-y.
APA：
Xuenong Ouyang,Meiqi Shi,Fangwei Jie,Yuxian Bai,Peng Shen...&Jifeng Feng.(2018).Phase III study of dulanermin (recombinant human tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand) combined with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer.INVESTIGATIONAL NEW DRUGS,36,(2)
MLA：
Xuenong Ouyang,et al."Phase III study of dulanermin (recombinant human tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand) combined with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer".INVESTIGATIONAL NEW DRUGS 36..2(2018):315-322
