Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial - 02/09/13

Doi : 10.1016/S1470-2045(13)70355-3

Yuankai Shi, MD ^a,^b,^{^{†
These authors contributed equally}}, Li Zhang, MD ^c,^{^{†
These authors contributed equally}}, Xiaoqing Liu, MD ^d, Caicun Zhou, MD ^e, Li Zhang, MD ^f, Shucai Zhang, MD ^g, Dong Wang, MD ^h, Qiang Li, MD ⁱ, Shukui Qin, MD ^j, Chunhong Hu, MD ^k, Yiping Zhang, MD ^l, Jianhua Chen, MD ^m, Ying Cheng, MD ⁿ, Jifeng Feng, MD ^o, Helong Zhang, MD ^p, Yong Song, MD ^r, Yi-Long Wu, MD ^s, Nong Xu, MD ^t, Jianying Zhou, MD ^t, Rongcheng Luo, MD ^u, Chunxue Bai, MD ^v, Yening Jin, MD ^w, Wenchao Liu, MD ^q, Zhaohui Wei, PhD ^x, Fenlai Tan, MD ^y, Yinxiang Wang, PhD ^y, Lieming Ding, MD ^y, Hong Dai, MD ^z, Shunchang Jiao, MD ^aa, Jie Wang, MD ^ab, Li Liang, MD ^ac, Weimin Zhang, MD ^ad, Yan Sun, ProfMD ^a,^⁎
^a Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
^b Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China
^c Sun Yat-Sen University Cancer Center, Guangzhou, China
^d Department of Pulmonary Oncology, 307 Hospital of the Academy of Military Medical Sciences, Cancer Center, Beijing, China
^e Shanghai Pulmonary Hospital, Tongji University, Shanghai, China
^f Peking Union Medical Hospital, Beijing, China
^g Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
^h Daping Hospital, Third Military Medical University, Chongqing, China
ⁱ Changhai Hospital, Second Military Medical University, Shanghai, China
^j Nanjing Bayi Hospital of People’s Liberation Army, Nanjing, China
^k Second Xiangya Hospital of Central South University, Changsha, China
^l Zhejiang Cancer Hospital, Hangzhou, China
^m Hunan Cancer Hospital, Changsha, China
ⁿ Jilin Province Cancer Hospital, Changchun, China
^o Jiangsu Province Cancer Hospital, Nanjing, China
^p Tangdu Hospital, Fourth Military Medical University, Xi’an, China
^q Xijing Hospital, Fourth Military Medical University, Xi’an, China
^r Nanjing Military General Hospital, Nanjing, China
^s Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
^t First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China
^u Nanfang Hospital, Southern Medical University, Guangzhou, China
^v Affiliated Zhongshan Hospital of Fudan University, Shanghai, China
^w Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China
^x Hangzhou Tigermed Consulting, Hangzhou, China
^y Zhejiang Beta Pharma, Hangzhou, China
^z Beijing Chao-Yang Hospital, Beijing, China
^aa General Hospital of People’s Liberation Army, Beijing, China
^ab Beijing Cancer Hospital, Beijing, China
^ac Peking University Third Hospital, Beijing, China
^ad Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China

^*Correspondence to: Prof Yan Sun, Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, 100021, China

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.

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Plan

Introduction

Methods

Study design and patients

Randomisation and masking

Procedures

Statistical analysis

Role of the funding source

Results

Discussion

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Vol 14 - N° 10

P. 953-961 - septembre 2013 Retour au numéro

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Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial - 02/09/13

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