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

作者全名："Yang, Yunpeng; Min, Jie; Yang, Nong; Yu, Qitao; Cheng, Ying; Zhao, Yanqiu; Li, Manxiang; Chen, Hong; Ren, Shouan; Zhou, Jianying; Zhuang, Wu; Qin, Xintian; Cao, Lejie; Yu, Yan; Zhang, Jian; He, Jianxing; Feng, Jifeng; Yu, Hao; Zhang, Li; Fang, Wenfeng"

作者地址："[Yang, Yunpeng; Zhang, Li; Fang, Wenfeng] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept Med Oncol, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Peoples R China; [Min, Jie] AF Med Univ, Affiliated Hosp 2, Dept Oncol, Xian 710038, Peoples R China; [Yang, Nong] Cent South Univ, Dept Med Oncol, Lung Canc & Gastrointestinal Unit, Hunan Canc Hosp,Affiliated Canc Hosp,Xiangya Sch M, Changsha 410013, Peoples R China; [Yu, Qitao] Guangxi Med Univ, Affiliated Tumor Hosp, Dept Med Oncol Resp, Nanning 530021, Guangxi, Peoples R China; [Cheng, Ying] Jilin Prov Canc Hosp, Dept Thorac Med Oncol, Changchun 130012, Peoples R China; [Zhao, Yanqiu] Zhengzhou Univ, Affiliated Canc Hosp, Dept Med Oncol, Zhengzhou 450003, Peoples R China; [Li, Manxiang] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Resp, Xian 710061, Peoples R China; [Chen, Hong] Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing 400050, Peoples R China; [Ren, Shouan] Shanxi Med Univ, Hosp 1, Dept Resp, Taiyuan 030001, Peoples R China; [Zhou, Jianying] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Resp Dis, Hangzhou 310003, Peoples R China; [Zhuang, Wu] Fujian Canc Hosp, Dept Med Oncol, Fuzhou 350014, Peoples R China; [Qin, Xintian] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Dept Oncol 1, Guangzhou 510699, Peoples R China; [Cao, Lejie] Anhui Prov Hosp, Dept Resp & Crit Care Med, Hefei 230000, Peoples R China; [Yu, Yan] Harbin Med Univ, Affiliated Canc Hosp, Dept Resp Med, Harbin 150000, Peoples R China; [Zhang, Jian] AF Med Univ, Affiliated Hosp 1, Dept Resp Med, Xian 710032, Peoples R China; [He, Jianxing] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Res Inst Resp Dis, Dept Cardiothorac Surg, Guangzhou 510120, Peoples R China; [He, Jianxing] China State Key Lab Resp Dis, Guangzhou 510120, Peoples R China; [Feng, Jifeng] Nanjing Med Univ, Affiliated Canc Hosp, Dept Med Oncol, Jiangsu Canc Hosp,Jiangsu Inst Canc Res, Nanjing 210009, Peoples R China; [Yu, Hao] Nanjing Med Univ, Dept Biostat, Nanjing 211166, Peoples R China"

通信作者："Zhang, L; Fang, WF (通讯作者)，Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept Med Oncol, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Peoples R China."

来源：SIGNAL TRANSDUCTION AND TARGETED THERAPY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001048628000003

JCR分区：Q1

影响因子：40.8

年份：2023

卷号：8

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

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 & GE;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."

基金机构：National Natural Science Foundation Project of China [82072558]

基金资助正文：AcknowledgementsThis study was funded by the National Natural Science Foundation Project of China (Grant No. 82072558).