机构：[1]Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, GuangdongProvincial People’s Hospital and Guangdong Academy of MedicalSciences, Guangzhou, China广东省人民医院[2]Department of Medical Oncology, Second ChestCancer Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of XiangyaSchool of Medicine, Central South University, Changsha, China[3]ClinicalPharmacology Research Center, Peking Union Medical College Hospital, ChineseAcademy of Medical Sciences & Peking Union Medical College, Beijing, China[4]Department of Thoracic Oncology, Peking University Cancer Hospital &Institute, Beijing, China[5]Department of Respiratory Medicine, The First AffiliatedHospital, Zhejiang University School of Medicine, Hangzhou, China[6]Department of Respiratory and Critical Care Medicine, Peking Union MedicalCollege Hospital, Chinese Academy of Medical Sciences & Peking Union MedicalCollege, Beijing, China[7]Department of Lung Cancer, Fifth Medical Center of PLAGeneral Hospital, Beijing, China[8]Lung Cancer Center, West China Hospital ofSichuan University, Chengdu, China[9]Division of Thoracic Oncology, JilinProvincial Cancer Hospital, Changchun, China[10]Department of MedicalOncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central SouthUniversity, Changsha, China[11]Department of Medical Oncology, ChinaNational Cancer Center/China Cancer Research Foundation/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing, China[12]The Affiliated Cancer Hospital of Nanjing Medical University,Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing,Jiangsu, China[13]Department of Pulmonary Medicine, Shanghai ChestHospital, Shanghai Jiao Tong University, Shanghai 200030, China[14]Department of Respiratory and Critical Care Medicine, Jinling Hospital,Nanjing University School of Medicine, Nanjing, China[15]Department ofRespiratory Medicine, The Second Affiliated Hospital, Zhejiang UniversitySchool of Medicine, Hangzhou, China[16]Department of Medical Oncology,State Key Laboratory of Oncology in South China, Collaborative InnovationCenter for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou,China[17]Oncology Department, Chinese PLA General Hospital, Beijing,China[18]Department of Oncology, The First Affiliated Hospital with NanjingMedical University, Nanjing, China[19]Department of Medical Oncology, FujianMedical University Union Hospital, Fuzhou, China[20]ACEA PharmaceuticalResearch, Hangzhou, China[21]ACEA Therapeutics Inc.,San Diego, California
To establish RP2D in Phase 1 and evaluate safety and efficacy of abivertinib in EGFR T790M+ NSCLC patients with disease progression from prior EGFR inhibitors in Phase 2.This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50mg BID to 350 mg BID was evaluated in Phase 1 in continual 28-day cycles, and the RP2D of 300 mg BID was used in Phase 2 in continual 21-day cycles. Primary endpoints include RP2D in phase 1 and objective response rate (ORR) at RP2D in phase 2.The RP2D of 300 mg BID for abivertinib was established based on pharmacokinetics, efficacy and safety profiles across doses in Phase 1. In Phase 2, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43-129). Among 209 response evaluable patients, confirmed ORR was 52.2% (109/209; 95% CI: 45.2%, 59.1%). Disease control rate (DCR) was 88.0% (184/209, 95% CI: 82.9%, 92.1%). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1, 9.2) and 7.5 months (95% CI: 6.0, 8.8), respectively. The median OS was 24.9 months (95% CI: 22.4, NR). All (227/227) patients reported at least 1 AE, with 96.9% (220/227) of treatment-related AE. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment related.Abivertinib of 300 mg BID demonstrated favorable clinical efficacy with manageable side-effects in patients with EGFR T790M+NSCLC.
基金：
This research was supported by Key Lab System Project of Guangdong Science
and Technology Department – Guangdong Provincial Key Lab of Translational
Medicine in Lung Cancer (Grant No. 2017B030314120, to Y.L. Wu); High-level
Hospital Construction Project (Grant No. DFJH201810, to Q. Zhou); and
National Science and Technology Infrastructure Program (National Key Science
Projects Program, Grant No. 2018ZX09301–014–002, to W.H. Xu, W. Tang, X.
Zhang, and X. Xiao).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|1 区医学
小类|1 区肿瘤学
最新[2023]版：
大类|1 区医学
小类|1 区肿瘤学
第一作者：
第一作者机构：[1]Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, GuangdongProvincial People’s Hospital and Guangdong Academy of MedicalSciences, Guangzhou, China
通讯作者：
通讯机构：[1]Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, GuangdongProvincial People’s Hospital and Guangdong Academy of MedicalSciences, Guangzhou, China[*1]Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, No. 106 Zhongshan 2nd Road, Guangzhou 510080, China
推荐引用方式(GB/T 7714)：
Qing Zhou,Lin Wu,Pei Hu,et al.A novel third generation EGFR tyrosine kinase inhibitor Abivertinib for EGFR T790M mutant Non-Small Cell Lung Cancer: a multicenter phase1/2 study.[J].Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research.2021,doi:10.1158/1078-0432.CCR-21-2595.
APA：
Qing Zhou,Lin Wu,Pei Hu,Tongtong An,Jianying Zhou...&Yi-Long Wu.(2021).A novel third generation EGFR tyrosine kinase inhibitor Abivertinib for EGFR T790M mutant Non-Small Cell Lung Cancer: a multicenter phase1/2 study..Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research,,
MLA：
Qing Zhou,et al."A novel third generation EGFR tyrosine kinase inhibitor Abivertinib for EGFR T790M mutant Non-Small Cell Lung Cancer: a multicenter phase1/2 study.".Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research .(2021)
医学