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

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• 作者：Prof Li Zhang ; MD^a ; ^{li-zhang@csco.org.cn} ; Shenglin Ma ; MD^b ; Xiangqun Song ; MSc^c ; Baohui Han ; MD^d ; Ying Cheng ; MSc^e ; Cheng Huang ; MD^f ; Shujun Yang ; MD^g ; Xiaoqing Liu ; MD^h ; Yunpeng Liu ; MDⁱ ; Shun Lu ; MD^j ; Jie Wang ; MD^k ; Shucai Zhang ; MD^l ; Caicun Zhou ; MD^m ; Xiangwei Zhang ; MDⁿ ; Nobuya Hayashi ; BA^o ; Mengzhao Wang ; MD^p ; on behalf of the INFORM investigators^&Dagger ;
• 刊名：Lancet Oncology
• 出版年：2012
• 期刊代码：184_14702045
• 类别：med
• 出版时间：May, 2012
• 卷：13
• 期：5
• 页码：466-475
• 文件大小：371 K

摘要

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Summary

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 , number .

Findings

Progression-free survival was significantly longer with gefitinib (n=148) than with placebo (148) (median progression-free survival 4路8 months [95%CI 3路2-8路5] vs 2路6 months [1路6-2路8]; hazard ratio [HR] 0路42, 95%CI 0路33-0路55; p<0路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.

Funding

AstraZeneca.