Bevacizumab biosimilar LY01008 compared with bevacizumab (Avastin) as first-line treatment for Chinese patients with unresectable, metastatic, or recurrent non-squamous non–small-cell lung cancer: A multicenter, randomized, double-blinded, phase III trial

Cancer Communications

article

Yuankai Shi¹  Kaijian Lei²  Yuming Jia²  Bingqiang Ni³  Zhiyong He⁴  Minghong Bi⁵  Xicheng Wang⁶  Jianhua Shi⁷  Ming Zhou⁸  Qian Sun⁹  Guolei Wang⁹  Dongji Chen^1,10  Yongqian Shu^1,11  Lianke Liu^1,11  Zhongliang Guo^1,12  Yong Liu^1,13  Junquan Yang^1,14  Ke Wang^1,15  Ke Xiao^1,16  Lin Wu^1,17  Tienan Yi^1,18  Debin Sun^1,19  Mafei Kang^2,20  Tianjiang Ma^2,21  Yimin Mao^2,22  Jinsheng Shi^2,23  Tiegang Tang^2,24  Yan Wang¹  Puyuan Xing¹  Dongqing Lv^2,25  Wangjun Liao^2,26  Zhiguo Luo^2,27  Bin Wang^2,28  Xiaohong Wu^2,29  Xiaoli Zhu^3,30  Shuhua Han^3,30  Qisen Guo^3,31  Rongyu Liu^3,32  Zhiwei Lu^3,33  Jianyong Zhang^3,34  Jian Fang^3,35  Changlu Hu^3,36  Yinghua Ji^3,37  Guolong Liu^3,38  Hong Lu^3,39  Dedong Wu^4,40  Junhong Zhang^4,41  Shuyang Zhu^4,42  Zheng Liu^4,43  Wensheng Qiu^4,44  Feng Ye^4,45  Yan Yu^4,46  Yanqiu Zhao^4,47  Qinhong Zheng^4,48  Jun Chen^4,49  Zhanyu Pan^5,50  Yiping Zhang^5,51  Wenjuan Lian^5,52  Bo Jiang^5,53  Bo Qiu^5,54  Guojun Zhang^5,55  Hua Zhang^5,56  Yanju Chen^5,57  Yuan Chen^5,58  Hongbing Duan^5,59  Manxiang Li^6,60  Shengming Liu^6,61  Lijun Ma^6,62  Hongming Pan^6,63  Xia Yuan^6,64  Xueli Yuan^6,65  Yulong Zheng^6,66  Emei Gao^6,67  Li Zhao^6,67  Shumin Wang^6,67  Can Wu^6,67 

[1] Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs;Department of Oncology, Yibin Second People's Hospital;Department of Oncology, Liuzhou People's Hospital;Department of Thoracic Oncology, Fujian Provincial Cancer Hospital;Oncology Department, the First Affiliated Hospital of Bengbu Medical College;Department of Oncology, the First Affiliated Hospital of Guangdong Pharmaceutical University;Department of Internal medicine, Linyi Cancer Hospital;Department of Thoracic Surgery, the Affiliated Cancer Hospital of Guangzhou Medical University;Department of Internal Medicine-Oncology/Department of thoracic oncology, Henan Chest Hospital;The Second Department of Radiotherapy, Wuwei Cancer Hospital of Gansu Province;Department of Oncology, the People's Hospital of Jiangsu Province;Respiratory Medicine Department, Shanghai East Hospital;The Second Department of Internal Medicine-Oncology, Xuzhou Central Hospital;Oncology Department, Tangshan People's Hospital;Respiratory Medicine Department, West China Hospital of Sichuan University;Thoracic Surgery, the Second Affiliated Hospital of Shantou University Medical College;Internal Medicine-Oncology, Hunan Cancer Hospital;Department of Oncology, Xiangyang Central Hospital;Respiratory Department, Lishui Central Hospital;Oncology Department, The Affiliated Hospital of Guilin Medical College;Internal Medicine-Oncology, Luohe Central Hospital;Respiratory Department, the First Affiliated Hospital of Henan University of Science and Technology;Oncology Department, Cangzhou People's Hospital;Oncology Department, Xiangtan Central Hospital;Respiratory Department, Taizhou Hospital of Zhejiang Province;Department of Oncology, Nanfang Hospital of Southern Medical University;Department of Oncology, Taihe Hospital of Shiyan City;Respiratory Department, Huzhou Central Hospital;Internal Medicine-Oncology, the Fourth People's Hospital of Wuxi City;Department of Oncology, Zhongda Hospital of Southeast University;The Second Department of Internal Medicine, Shandong Cancer Hospital;Respiratory Department, the First Affiliated Hospital of Anhui Medical University;Respiratory Department, The First Affiliated Hospital of Wannan Medical College;The Second Department of Respiratory Medicine, the Affiliated Hospital of Zunyi Medical College;The Second Department of thoracic oncology, Beijing Cancer Hospital;Department of Oncology, Anhui Cancer Hospital;Oncology Department, the First Affiliated Hospital of Xinxiang Medical College;Department of Oncology, the First People's Hospital of Guangzhou;Oncology Department, Huaihe Hospital of Henan University;Department of Oncology and Hematology, The First People's Hospital of Zhengzhou;Oncology Department, Zhongnan Hospital of Wuhan University;Respiratory Department, The Affiliated Hospital of Xuzhou Medical University;The Third Department of Oncology, Handan Central Hospital;Oncology Department, The Affiliated Hospital of Qingdao University;Oncology Department, the First Affiliated Hospital of Xiamen University;The Sixth Department of Internal Medicine, the Affiliated Cancer Hospital of Harbin Medical University;Respiratory Department, Henan Cancer Hospital;Internal Medicine-Oncology, Quzhou People's Hospital;Lung tumor surgery Department, General Hospital of Tianjin Medical University;Integrated Traditional Chinese and Western Medicine Department, Tianjin Cancer Hospital;Department of Thoracic Cancer, Zhejiang Cancer Hospital;Department of Oncology, Xi'an Chest Hospital;Special Medical Treatment, Yunnan Cancer Hospital;Department of Oncology, Zhuzhou Central Hospital;Respiratory Department, The First Affiliated Hospital of Zhengzhou University;Second Department of Cancer Center, The First Affiliated Hospital of Xinjiang Medical University;Internal Medicine-Oncology, Hainan Provincial People's Hospital;Oncology Department, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology;Thoracic Surgery, Zhongshan Hospital Affiliated to Xiamen University;Respiratory Department, The First Affiliated Hospital of Xi'an Jiaotong University;Respiratory Department, The First Affiliated Hospital of Jinan University;Oncology Department, Shanghai Tongren Hospital;Internal Medicine-Oncology, Shaoyifu Hospital Affiliated to Medical College of Zhejiang University;Internal Medicine-Oncology, Huizhou Central People's Hospital;Oncology Department, the Fourth Affiliated Hospital of Harbin Medical University;Respiratory Department, Huai'an Second People's Hospital;Clinical Research Center of Luye Pharma Group Ltd, Luye Life Sciences Group

关键词: anti-angiogenesis;    anti-VEGF monoclonal antibody;    avastin;    bevacizumab;    biosimilar;    non-small cell lung cancer;    LY01008;    vascular endothelial growth factor;   

DOI  :  10.1002/cac2.12179

学科分类：社会科学、人文和艺术（综合）

来源: Springer

【 摘 要 】

Background Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). Methods Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). Results Between December 15 th , 2017, and May 15 th , 2019, a total of 649 patients were randomized to the LY01008 ( n = 324) or Avastin ( n = 325) group. As of September 25 th , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15 th , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. Conclusions LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting.

【 授权许可】

CC BY|CC BY-NC-ND