- 作者：Yuankai Shi ; Li Zhang ; Xiaoqing Liu ; Caicun Zhou ; Li Zhang ; Shucai Zhang ; Dong Wang ; Qiang Li ; Shukui Qin ; Chunhong Hu ; Yiping Zhang ; Jianhua Chen ; Ying Cheng ; Jifeng Feng ; Helong Zhang ; Yong Song ; Yi-Long Wu ; Nong Xu ; Jianying Zhou ; Rongcheng Luo ; et al.
- 刊名：Lancet Oncology
- 出版年：2013
- 出版时间：September, 2013
- 年：2013
- 卷：14
- 期：10
- 页码：953-961
- 全文大小：490 K
Summary
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 , number , 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.
Funding
Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.