|Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial|
|Zhang, Li1; Ma, Shenglin2; Song, Xiangqun3; Han, Baohui4; Cheng, Ying5; Huang, Cheng6; Yang, Shujun7; Liu, Xiaoqing8; Liu, Yunpeng9; Lu, Shun10; Wang, Jie11; Zhang, Shucai12; Zhou, Caicun13; Zhang, Xiangwei14; Hayashi, Nobuya15; Wang, Mengzhao16; INFORM Investigators|
|WOS标题词||Science & Technology|
|关键词[WOS]||QUALITY-OF-LIFE ; CLINICALLY SELECTED PATIENTS ; III TRIAL ; 1ST-LINE CHEMOTHERAPY ; FUNCTIONAL ASSESSMENT ; JAPANESE PATIENTS ; SUPPORTIVE CARE ; ADVANCED NSCLC ; CARBOPLATIN ; DOCETAXEL|
Background Maintenance treatment of patients with advanced non-small-cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of the randomised, double-blind, placebo-controlled, INFORM study was to investigate the efficacy, safety, and tolerability of the EGFR-tyrosine-kinase inhibitor gefitinib in the maintenance setting.
Methods Patients were aged 18 years or older, were of east Asian ethnic origin, had a life expectancy of more than 12 weeks, histologically or cytologically confirmed stage IIIb or IV NSCLC, a WHO performance status of 0-2, and had completed four cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects. Between Sept 28, 2008 and Aug 11, 2009, 296 patients were randomly assigned 1: 1 to receive either gefitinib (250 mg per day orally) or placebo (orally) within 3-6 weeks after chemotherapy until progression or unacceptable toxic effects. Randomisation was done via an interactive web response system with computer-generated randomisation codes. Our primary endpoint was progression-free survival assessed in the intention-to-treat population. This completed study is registered with Clinicaltrials.gov, number NCT00770588.
Findings Progression-free survival was significantly longer with gefitinib (n=148) than with placebo (148) (median progression-free survival 4.8 months [95% CI 3.2-8.5] vs 2.6 months [1.6-2.8]; hazard ratio [HR] 0.42, 95% CI 0.33-0.55; p<0.0001). Adverse events occurred more frequently with gefitinib than with placebo; the most common adverse events of any grade were rash (73 [50%] of 147 in the gefitinib group vs 14 [9%] of 148 in the placebo group), diarrhoea (37 [25%] vs 13 [9%]), and alanine aminotransferase increase (31 [21%] vs 12 [8%]). The most commonly reported grade 3 or 4 adverse event was alanine aminotransferase increase (3 [2%] of 147 in the gefitinib group, none of 148 in the placebo group). Ten of 147 (7%) patients given gefitinib and five of 148 (3%) patients given placebo had serious adverse events. Three deaths were thought to be related to treatment with gefitinib: one from interstitial lung disease; one from lung infection; and one from pneumonia.
Interpretation Maintenance treatment with gefitinib significantly prolonged progression-free survival compared with placebo in patients from east Asia with advanced NSCLC who achieved disease control after first-line chemotherapy. Clinicians should consider these data when making decisions about maintenance treatment in such patients.
|作者单位||1.Sun Yat Sen Univ, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China|
2.Zhejiang Canc Hosp, Dept Radiat Therapy, Hangzhou, Zhejiang, Peoples R China
3.Guangxi Zhuang Autonomous Reg Tumour Hosp, Nanning, Peoples R China
4.Shanghai Chest Hosp, Dept Pulm Med, Shanghai, Peoples R China
5.Jilin Prov Tumour Hosp, Changchun, Peoples R China
6.Fujian Prov Tumor Hosp, Fuzhou, Peoples R China
7.Henan Prov Tumour Hosp, Dept Chemotherapy, Zhengzhou, Peoples R China
8.Peoples Liberat Army, Hosp 307, Dept Oncol, Beijing, Peoples R China
9.China Med Univ, Hosp 1, Shenyang, Peoples R China
10.Beijing Chest Hosp, Dept Med Oncol, Beijing, Peoples R China
11.AstraZeneca, Shanghai, Peoples R China
12.AstraZeneca KK, Osaka, Japan
13.Shanghai Chest Hosp, Med Ctr, Lung Tumour Clin, Shanghai, Peoples R China
14.Beijing Canc Hosp, Dept Thorac Med Oncol, Beijing, Peoples R China
15.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Oncol, Shanghai 200092, Peoples R China
16.Peking Union Med Coll, Dept Resp Dis, Beijing 100021, Peoples R China
|Zhang, Li,Ma, Shenglin,Song, Xiangqun,et al. Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial[J]. LANCET ONCOLOGY,2012,13(5):466-475.|
|APA||Zhang, Li.,Ma, Shenglin.,Song, Xiangqun.,Han, Baohui.,Cheng, Ying.,...&INFORM Investigators.(2012).Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial.LANCET ONCOLOGY,13(5),466-475.|
|MLA||Zhang, Li,et al."Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial".LANCET ONCOLOGY 13.5(2012):466-475.|