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


RESULTS
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).


CONCLUSIONS
Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer.
Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yuankai
Y
Shi
Li
L
Zhang
Xiaoqing
X
Liu
Caicun
C
Zhou
Li
L
Zhang
Shucai
S
Zhang
Dong
D
Wang
Qiang
Q
Li
Shukui
S
Qin
Chunhong
C
Hu
Yiping
Y
Zhang
Jianhua
J
Chen
Ying
Y
Cheng
Jifeng
J
Feng
Helong
H
Zhang
Yong
Y
Song
Yi-Long
YL
Wu
Nong
N
Xu
Jianying
J
Zhou
Rongcheng
R
Luo
Chunxue
C
Bai
Yening
Y
Jin
Wenchao
W
Liu
Zhaohui
Z
Wei
Fenlai
F
Tan
Yinxiang
Y
Wang
Lieming
L
Ding
Hong
H
Dai
Shunchang
S
Jiao
Jie
J
Wang
Li
L
Liang
Weimin
W
Zhang
Yan
Y
Sun
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D043844:Crown Ethers / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D043844:Crown Ethers; D011799:Quinazolines; C531470:icotinib; D066246:ErbB Receptors; D000077156:Gefitinib