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

• Published in: The lancet oncology Vol. 14; no. 10; pp. 953 - 961
• Main Authors: Shi, Yuankai, MD, Zhang, Li, MD, Liu, Xiaoqing, MD, Zhou, Caicun, MD, Zhang, Shucai, MD, Wang, Dong, MD, Li, Qiang, MD, Qin, Shukui, MD, Hu, Chunhong, MD, Zhang, Yiping, MD, Chen, Jianhua, MD, Cheng, Ying, MD, Feng, Jifeng, MD, Zhang, Helong, MD, Song, Yong, MD, Wu, Yi-Long, MD, Xu, Nong, MD, Zhou, Jianying, MD, Luo, Rongcheng, MD, Bai, Chunxue, MD, Jin, Yening, MD, Liu, Wenchao, MD, Wei, Zhaohui, PhD, Tan, Fenlai, MD, Wang, Yinxiang, PhD, Ding, Lieming, MD, Dai, Hong, MD, Jiao, Shunchang, MD, Wang, Jie, MD, Liang, Li, MD, Zhang, Weimin, MD, Sun, Yan, Prof
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2013; Elsevier Limited
• Subjects: Antineoplastic Agents - therapeutic use; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Chemotherapy; Crown Ethers - adverse effects; Crown Ethers - therapeutic use; Disease-Free Survival; Double-Blind Method; Drug dosages; Female; Hematology, Oncology and Palliative Medicine; Humans; Kinases; Lung cancer; Lung diseases; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Metastasis; Middle Aged; Mutation; Quality of life; Quinazolines - adverse effects; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - genetics; Toxicity; China
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(13)70355-3

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 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. Funding Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.