Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib-refractory ALK-positive NSCLC from a phase II study  

作　　者：Jing Zheng Tao Wang Yunpeng Yang Jie Huang Jifeng Feng Wu Zhuang Jianhua Chen Jun Zhao Wei Zhong Yanqiu Zhao Yiping Zhang Yong Song Yi Hu Zhuang Yu Youling Gong Yuan Chen Feng Ye Shucai Zhang Lejie Cao Yun Fan Gang Wu Yubiao Guo Chengzhi Zhou Kewei Ma Jian Fang Weineng Feng Yunpeng Liu Zhendong Zheng Gaofeng Li Huijie Wang Shundong Cang Ning Wu Wei Song Xiaoqing Liu Shijun Zhao Lieming Ding Giovanni Selvaggi Yang Wang Shanshan Xiao Qian Wang Zhilin Shen Jianya Zhou Jianying Zhou Li Zhang 

机构地区：[1]Department of Respiratory Disease,Thoracic Disease Center,The First Affiliated Hospital,College of Medicine,Zhejiang University,Zhejiang Provincial Clinical Research Center for Respiratory Disease,Hangzhou,Zhejiang,P.R.China [2]Hangzhou Repugene Technology Co.,Ltd,Hangzhou,Zhejiang,P.R.China [3]Department of Medical Oncology,Sun Yat-sen University Cancer Cen-ter,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangzhou,Guangdong,P.R.China [4]Department of Medical Oncology,Jiangsu Cancer Hospital,Jiangsu Institute of Cancer Research,The Affiliated Cancer Hospital of Nanjing Medical University,Nanjing,Jiangsu,P.R.China [5]Department of Thoracic Oncology,Fujian Provincial Cancer Hospital,Fujian Medical University Cancer Hospital,Fuzhou,Fujian,P.R.China [6]Department of Medical Oncology-Chest,Hunan Cancer Hospital,Changsha,Hunan,P.R.China [7]Department of Thoracic Oncology,Beijing Cancer Hospital,Beijing,P.R.China [8]Department of Pulmonary Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing,P.R.China [9]Respiratory Department of Internal Medicine,Henan Provincial Can-cer Hospital,Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou,Henan,P.R.China [10]Thoracic Medical Oncology,Zhejiang Cancer Hospital,Hangzhou,Zhejiang,P.R.China [11]Division of Respiratory Medicine,Jinling Hospital,Nanjing University School of Medicine,Nanjing,Jiangsu,P.R.China [12]Department of Oncology,Chinese People’s Liberation Army(PLA)General Hospital,Beijing,P.R.China [13]Department of Oncology,The Affiliated Hospital of Qingdao University,Qingdao,Shandong,P.R.China [14]Department of Thoracic Oncology,Cancer Center,West China Hospital,Sichuan University,Chengdu,Sichuan,P.R.China [15]Department of Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,P.R.China [16]Department of Medical Oncology,Cancer Hospital,The First Affiliated Hospital of Xiamen University,S

出　　处：《Cancer Communications》2024年第4期455-468,共14页癌症通讯（英文）

摘　　要：Background:The initial phase II stuty(NCT03215693)demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory,anaplastic lymphoma kinase(ALK)-positive non-small cell lung cancer(NSCLC).Herein,we reported the updated data on overall survival(OS)and molecular profiling from the initial phase Ⅱ study.Methods:In this study,180 patients received 225 mg of ensartinib orally once daily until disease progression,death or withdrawal.OS was estimated by Kaplan‒Meier methods with two-sided 95%confidence intervals(CIs).Next-generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib.Circulating tumor DNA(ctDNA)was detected to dynamically monitor the genomic alterna-tions during treatment and indicate the existence of molecular residual disease,facilitating improvement of clinical management.Results:At the data cut-off date(August 31,2022),with a median follow-up time of 53.2 months,97 of 180(53.9%)patients had died.The median OS was 42.8 months(95%CI:29.3-53.2 months).A total of 333 plasma samples from 168 patients were included for ctDNA analysis.An inferior OS correlated sig-nificantly with baseline ALK or tumor protein 53(TP53)mutation.In addition,patients with concurrent TP53 mutations had shorter OS than those without con-current TP53 mutations.High ctDNA levels evaluated by variant allele frequency(VAF)and haploid genome equivalents per milliliter of plasma(hGE/mL)at baseline were associated with poor OS.Additionally,patients with ctDNA clear-ance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth,respectively.Furthermore,patients who had a lower tumor burden,as evaluated by the diameter of target lesions,had a longer OS.Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases,higher hGE,and elevated ALK mutation abundance at 6 weeks.Conclusion:Ensartinib led to a favorable

关 键 词：anaplastic lymphoma kinase CTDNA ensartinib non-small cell lung cancer overall survival 

分 类 号：R730.2[医药卫生—肿瘤]