Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial  

作　　者：Yunpeng Yang Jie Min Nong Yang Qitao Yu Ying Cheng Yanqiu Zhao Manxiang Li Hong Chen Shou’an Ren Jianying Zhou Wu Zhuang Xintian Qin Lejie Cao Yan Yu Jian Zhang Jianxing He Jifeng Feng Hao Yu Li Zhang Wenfeng Fang 

机构地区：[1]Department of Medical Oncology,Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangzhou 510060,China [2]Department of Oncology,The Second Affiliated Hospital of Air Force Medical University,Xi’an 710038,China [3]Department of Medical Oncology,Lung Cancer and Gastrointestinal Unit,Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University,Changsha 410013,China [4]Department of Medical Oncology of Respiratory,Affiliated Tumor Hospital of Guangxi Medical University,Guangxi,Nanning 530021,China [5]Department of Thoracic Medical Oncology,Jilin Provincial Cancer Hospital,Changchun 130012,China [6]Department of Medical Oncology,The Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450003,China [7]Department of Respiratory,First Affiliated Hospital of Xian Jiaotong University,Xi’an 710061,China [8]Department of Respiratory and Critical Care Medicine,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400050,China [9]Department of Respiratory,The First Hospital of Shanxi Medical University,Taiyuan 030001,China [10]Department of Respiratory Disease,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China [11]Department of Medical Oncology,Fujian Cancer Hospital,Fuzhou 350014,China [12]The First Department of Oncology,The First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510699,China [13]Department of Respiratory and Critical Care Medicine,Anhui Provincial Hospital,Hefei 230000,China [14]Department of Respiratory Medicine,Affiliated Cancer Hospital of Harbin Medical University,Harbin 150000,China [15]Department of Respiratory Medicine,The First Affiliated Hospital of Air Force Medical University,Xi’an 710032,China [16]Department of Cardiothoracic Surgery,The First Affiliated Hospital of Guangzhou Medical College,Guangzhou Research Institute of Respiratory Disease and China State Key Laborat

出　　处：《Signal Transduction and Targeted Therapy》2023年第9期4338-4345,共8页信号转导与靶向治疗(英文)

基　　金：This study was funded by the National Natural Science Foundation Project of China(Grant No.82072558).

摘　　要：Anaplastic lymphoma kinase(ALK)rearrangements are present in about 5–6%of non-small cell lung cancer(NSCLC)cases and associated with increased risks of central nervous system(CNS)involvement.Envonalkib,a novel ALK inhibitor,demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study.This phase III trial(ClinicalTrials.gov NCT04009317)investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases.Totally 264 participants were randomized 1:1 to receive envonalkib(n=131)or crizotinib(n=133).Median independent review committee(IRC)-assessed progression-free survival(PFS)times were 24.87(95%confidence interval[CI]:15.64–30.36)and 11.60(95%CI:8.28–13.73)months in the envonalkib and crizotinib groups,respectively(hazard ratio[HR]=0.47,95%CI:0.34–0.64,p<0.0001).IRC-assessed confirmed objective response rate(ORR)was higher(81.68%vs.70.68%,p=0.056)and duration of response was longer(median,25.79[95%CI,16.53–29.47]vs.11.14[95%CI,9.23–16.59]months,p=0.0003)in the envonalkib group compared with the crizotinib group.In participants with baseline brain target lesions,IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib(78.95%vs.23.81%).Overall survival(OS)data were immature,and median OS was not reached in either group(HR=0.84,95%CI:0.48–1.47,p=0.5741).The 12-month OS rates were 90.6%(95%CI,84.0%–94.5%)and 89.4%(95%CI,82.8%–93.6%)in the envonalkib and crizotinib groups,respectively.Grade≥3 treatment-related adverse events were observed in 55.73%and 42.86%of participants in the envonalkib and crizotinib groups,respectively.Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC.

关 键 词：CRIZOTINIB RANDOMIZED cancer 

分 类 号：R734.2[医药卫生—肿瘤]