Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies

作者全名："Yang, Sheng; Wu, Shiman; Zhao, Yanqiu; Chen, Gongyan; Zhu, Bo; Li, Xingya; Wang, Ke; Shi, Jianhua; Cang, Shundong; Yao, Wenxiu; Fan, Yun; Fang, Jian; Zhang, Liangming; Zhou, Jianying; Wu, Lin; Zheng, Rongsheng; Huang, Meijuan; Pan, Yueyin; Yang, Zhixiong; Sun, Meili; Yu, Huiqing; Wang, Donglin; Huang, Jianan; Wang, Lijun; Shu, Yongqian; Chen, Zhaohong; Liu, Chunling; Li, Jingzhang; Liu, Jiwei; Sun, Shenghua; Guo, Yanzhen; Meng, Zili; Liu, Zhefeng; Han, Zhigang; Wu, Gang; Lu, Hong; Ma, Rui; Hu, Sheng; Zhao, Guofang; Zhang, Longzhen; Liu, Zheng; Xie, Congying; Zhong, Diansheng; Zhao, Hui; Bi, Minghong; Yi, Shanyong; Guo, Shuliang; Yi, Tienan; Li, Wen; Lin, Yingcheng; Chen, Zhendong; Zhuang, Zhixiang; Guo, Zhongliang; Greco, Michael; Wang, Tingting; Zhou, Anqi; Shi, Yuankai"

作者地址："[Yang, Sheng; Shi, Yuankai] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc,Dept Med Oncol ,Beijing Key, Beijing, Peoples R China; [Wu, Shiman] Shanxi Med Univ, Dept Resp Med, Hosp 1, Taiyuan, Peoples R China; [Zhao, Yanqiu] Zhengzhou Univ, Dept Resp Med, Affiliated Canc Hosp, Zhengzhou, Peoples R China; [Chen, Gongyan] Harbin Med Univ, Dept Resp Med, Canc Hosp, Harbin, Peoples R China; [Zhu, Bo] Third Mil Med Univ, Xinqiao Hosp, Inst Canc, Dept Oncol, Chongqing, Peoples R China; [Li, Xingya] Zhengzhou Univ, Dept Oncol, Affiliated Hosp 1, Zhengzhou, Peoples R China; [Wang, Ke] Sichuan Univ, Dept Resp & Crit Care Med, West China Hosp, Chengdu, Peoples R China; [Shi, Jianhua] Linyi Canc Hosp, Dept Med Oncol, Linyi, Peoples R China; [Cang, Shundong] Henan Prov Peoples Hosp, Dept Med Oncol, Zhengzhou, Peoples R China; [Yao, Wenxiu] Sichuan Canc Hosp, Dept Med Oncol, Chengdu, Peoples R China; [Fan, Yun] Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou, Peoples R China; [Fang, Jian] Beijing Canc Hosp, Dept Thorac Oncol, Beijing, Peoples R China; [Zhang, Liangming] Yantai Yuhuangding Hosp, Dept Med Oncol, Yantai, Peoples R China; [Zhou, Jianying] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Resp Med, Hangzhou, Peoples R China; [Wu, Lin] Cent South Univ, Hunan Canc Hosp, Xiangya Sch Med, Dept Thorac Med Oncol,Affiliated Canc Hosp, Changsha, Peoples R China; [Zheng, Rongsheng] Bengbu Med Coll, Dept Med Oncol, Affiliated Hosp 1, Bengbu, Peoples R China; [Huang, Meijuan] Sichuan Univ, West China Hosp, Thorac Oncol Ward, Div Med Oncol, Chengdu, Peoples R China; [Pan, Yueyin] Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Thorac Canc Chemotherapy, Div Life Sci & Med, Hefei, Peoples R China; [Yang, Zhixiong] Guangdong Med Univ, Canc Ctr, Affiliated Hosp, Zhanjiang, Peoples R China; [Sun, Meili] Shandong Univ, Dept Oncol, Jinan Cent Hosp, Jinan, Peoples R China; [Yu, Huiqing; Wang, Donglin] Chongqing Univ, Dept Palliat Care, Dept Geriatr Oncol, Canc Hosp, Chongqing, Peoples R China; [Huang, Jianan] Soochow Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, Suzhou, Peoples R China; [Wang, Lijun] Xingtai Med Coll, Canc Ctr, Affiliated Hosp 2, Xingtai, Peoples R China; [Shu, Yongqian] Jiangsu Prov Hosp, Dept Oncol, Nanjing, Peoples R China; [Chen, Zhaohong] Peoples Hosp Deyang City, Dept Oncol, Deyang, Peoples R China; [Liu, Chunling; Han, Zhigang] Xinjiang Med Univ, Pulm Canc Med, Affiliated Tumor Hosp, Urumqi, Peoples R China; [Li, Jingzhang] Liuzhou Peoples Hosp, Dept Oncol, Liuzhou, Peoples R China; [Liu, Jiwei] Dalian Med Univ, Dept Oncol, Affiliated Hosp 1, Dalian, Peoples R China; [Sun, Shenghua] Cent South Univ, Dept Resp Med, Third Xiangya Hosp, Changsha, Peoples R China; [Guo, Yanzhen] Henan Univ Sci & Technol, Dept Med Oncol, Affiliated Hosp 1, Luoyang, Peoples R China; [Meng, Zili] Nanjing Med Univ, Dept Resp Med, Affiliated Huaian 1 Peoples Hosp, Huaian, Peoples R China; [Liu, Zhefeng] Chinese Peoples Liberat Army Gen Hosp, Dept Oncol, Beijing, Peoples R China; [Wu, Gang] Liaoning Canc Hosp & Inst, Dept Thorac Oncol, Shenyang, Peoples R China; [Wu, Gang] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Canc Ctr, Wuhan, Peoples R China; [Lu, Hong] Henan Univ, Dept Oncol, Huaihe Hosp, Kaifeng, Peoples R China; [Ma, Rui] Univ Chinese Acad Sci, Hwa Mei Hosp, Dept Thorac Surg, Ningbo, Peoples R China; [Liu, Zheng] Xuzhou Med Univ, Dept Radiotherapy, Affiliated Hosp, Xuzhou, Peoples R China; [Xie, Congying] HanDan Cent Hosp, Dept Oncol, Handan, Peoples R China; [Zhong, Diansheng] Wenzhou Med Univ, Dept Radiotherapy, Affiliated Hosp 1, Wenzhou, Peoples R China; [Zhao, Hui] Bengbu Med Coll, Dept Med Oncol, Affiliated Hosp 1, Bengbu, Peoples R China; [Bi, Minghong] Tianjin Med Univ, Dept Med Oncol, Gen Hosp, Tianjin, Peoples R China; [Yi, Shanyong] Anhui Med Univ, Dept Resp Med, Hosp 2, Hefei, Peoples R China; [Guo, Shuliang] Zhengzhou Univ, Dept Med Oncol, Zhengzhou Cent Hosp, Zhengzhou, Peoples R China; [Yi, Tienan] Chongqing Med Univ, Dept Resp Med, Affiliated Hosp 1, Chongqing, Peoples R China; [Li, Wen] Hubei Univ Arts & Sci, Xiangyang Cent Hosp, Dept Oncol, Affiliated Hosp, Xiangyang, Peoples R China; [Lin, Yingcheng] Zhejiang Univ, Dept Resp & Crit Care Med, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China; [Lin, Yingcheng] Shantou Univ, Dept Med Oncol, Canc Hosp, Med Coll, Shantou, Peoples R China; [Chen, Zhendong] Anhui Med Univ, Dept Oncol, Hosp 2, Hefei, Peoples R China; [Zhuang, Zhixiang] Soochow Univ, Dept Oncol, Affiliated Hosp 2, Suzhou, Peoples R China; [Guo, Zhongliang] Shanghai East Hosp, Dept Resp Med, Shanghai, Peoples R China; [Greco, Michael] Beta Pharm Inc, Dept Drug Discovery, Princeton, NJ USA; [Wang, Tingting; Zhou, Anqi] Beta Pharm Shanghai Co Ltd, Dept Clin Dev, Shanghai, Peoples R China; [Shi, Yuankai] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc,Dept Med Oncol ,Beijing Key, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China"

通信作者："Shi, YK (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc,Dept Med Oncol ,Beijing Key, Beijing, Peoples R China.; Shi, YK (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc,Dept Med Oncol ,Beijing Key, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China."

来源：LUNG CANCER

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001015396600001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：180

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Rezivertinib; BPI-7711; EGFR T790M mutation; CNS; NSCLC

摘要："Background: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyro-sine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here.Methods: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (& GE;180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated.Results: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were-52.0% (range:-100.0 to 16.1%) and-46.8% (95% CI: -55.5 to-38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months.Conclusions: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases."

基金机构："Beta Pharma (Shanghai) Co., Ltd. Shanghai, People's Republic of China [NCT03812809, 81972805]; Shanghai, People's Republic of China; China National Major Project for New Drug Innovation [NCT03386955]; New National Natural Science Foundation of China [82172856]; [2017ZX09304015]"

基金资助正文："In this pooled analysis, both previous clinical studies (NCT03386955; NCT03812809) were funded by Beta Pharma (Shanghai) Co., Ltd. Shanghai, People's Republic of China, and partly supported by the China National Major Project for New Drug Innovation (2017ZX09304015) and the New National Natural Science Foundation of China (81972805; 82172856)."