Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial

被引：777

作者：

Shi, Yuankai ^{[1
,2
]}

Zhang, Li ^{[3
,6
]}

Liu, Xiaoqing ^{[4
]}

Zhou, Caicun ^{[5
]}

Zhang, Li ^{[3
,6
]}

Zhang, Shucai ^{[7
]}

Wang, Dong ^{[8
,25
]}

Li, Qiang ^{[9
]}

Qin, Shukui ^{[10
]}

Hu, Chunhong ^{[11
]}

Zhang, Yiping ^{[12
]}

Chen, Jianhua ^{[13
]}

Cheng, Ying ^{[14
]}

Feng, Jifeng ^{[15
]}

Zhang, Helong ^{[16
]}

Song, Yong ^{[18
]}

Wu, Yi-Long ^{[19
]}

Xu, Nong ^{[20
]}

Zhou, Jianying ^{[20
]}

Luo, Rongcheng ^{[21
]}

Bai, Chunxue ^{[22
]}

Jin, Yening ^{[23
]}

Liu, Wenchao ^{[17
]}

Wei, Zhaohui ^{[24
]}

Tan, Fenlai ^{[25
]}

Wang, Yinxiang

Ding, Lieming ^{[25
]}

Dai, Hong ^{[26
]}

Jiao, Shunchang

Wang, Jie

Liang, Li

Zhang, Weimin

Sun, Yan ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Med Oncol, Beijing 100730, Peoples R China

[2] Key Lab Clin Study Anticanc Mol Targeted Drugs, Beijing, Peoples R China

[3] Sun Yat Sen Univ, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China

[4] Acad Mil Med Sci, Ctr Canc, Dept Pulm Oncol, Hosp 307, Beijing, Peoples R China

[5] Tongji Univ, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China

[6] Peking Union Med Hosp, Beijing, Peoples R China

[7] Capital Med Univ, Beijing TB & Thorac Tumor Res Inst, Dept Med Oncol, Beijing Chest Hosp, Beijing, Peoples R China

[8] Third Mil Med Univ, Daping Hosp, Chongqing, Peoples R China

[9] Second Mil Med Univ, Changhai Hosp, Shanghai, Peoples R China

[10] Nanjing Bayi Hosp Peoples Liberat Army, Nanjing, Jiangsu, Peoples R China

[11] Cent S Univ, Xiangya Hosp 2, Changsha, Hunan, Peoples R China

[12] Zhejiang Canc Hosp, Hangzhou, Zhejiang, Peoples R China

[13] Hunan Canc Hosp, Changsha, Hunan, Peoples R China

[14] Jilin Prov Canc Hosp, Changchun, Peoples R China

[15] Jiangsu Prov Canc Hosp, Nanjing, Jiangsu, Peoples R China

[16] Tangdu Hosp, Xian, Peoples R China

[17] Xijing Hosp, Xian, Peoples R China

[18] Fourth Mil Med Univ, Nanjing Mil Gen Hosp, Xian 710032, Peoples R China

[19] Guangdong Acad Med Sci, Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China

[20] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China

[21] Southern Med Univ, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China

[22] Fudan Univ, Affiliated Zhongshan Hosp, Shanghai 200433, Peoples R China

[23] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai 200030, Peoples R China

[24] Hangzhou Tigermed Consulting, Hangzhou, Zhejiang, Peoples R China

[25] Zhejiang Beta Pharma, Hangzhou, Zhejiang, Peoples R China

[26] Beijing Chao Yang Hosp, Beijing, Peoples R China

来源：

LANCET ONCOLOGY | 2013年 / 14卷 / 10期

关键词：

TYROSINE KINASE INHIBITOR; RECEPTOR GENE-MUTATIONS; ERLOTINIB; EGFR; DOCETAXEL;

D O I：

10.1016/S1470-2045(13)70355-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1: 1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1.14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n = 199; gefitinib, n = 196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0.84, 95% CI 0.67-1.05; median progression-free survival 4.6 months [95% CI 3.5-6.3] vs 3.4 months [2.3-3.8]; p = 0.13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p = 0.046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p = 0.033). Interpretation Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer.

引用

页码：953 / 961

页数：9

共 27 条

[1]

RELIABILITY AND VALIDITY OF THE FUNCTIONAL ASSESSMENT OF CANCER-THERAPY - LUNG (FACT-L) QUALITY-OF-LIFE INSTRUMENT [J].