Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial
Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial
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DOI：
10.1016/s1470-2045(12)70087-6
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发表时间：
2012-05-01
期刊：
影响因子：
51.1
通讯作者：
Yang, James Chih-Hsin
中科院分区：
文献类型：
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作者：
Miller, Vincent A.;Hirsh, Vera;Yang, James Chih-Hsin
背景：阿法替尼是一种不可逆erbb家族阻滞剂，在EGFR突变模型中显示出临床前活性，该模型具有对EGFR酪氨酸激酶抑制剂产生耐药性的突变。我们的目的是评估其在既往使用EGFR酪氨酸激酶抑制剂治疗失败的晚期肺腺癌患者中的疗效。在这项2b/3期试验中，研究人员招募了IIIB或IV期腺癌患者，这些患者既往接受过一种或两种化疗方案，并在厄洛替尼或吉非替尼治疗至少12周后出现疾病进展。我们使用计算机生成的序列随机分配患者（2:1）至阿法替尼组（每天50mg）或安慰剂组；所有患者均接受了最佳支持性护理。随机分组为3组，并根据性别和基线ECOG表现状态（0-1 vs 2）进行分层。研究者、患者和试验发起者对治疗分配不知情。主要终点是总生存期（从随机化日期到死亡），以意向治疗为基础进行分析。本研究已在ClinicalTrials.gov注册，注册号NCT00656136。在2008年5月26日至2009年9月21日期间，我们确定了697例患者，其中585例随机分配到治疗组（390例阿法替尼组，195例安慰剂组）。阿法替尼组中位总生存期为10.8个月（95% CI 10.0-12.0），安慰剂组中位总生存期为12.0个月（10.2-14.3）（风险比1.08,95% CI 0.86-1.35; p=0.74）。阿法替尼组的中位无进展生存期（3.3个月，95% CI 2.79-4.40）长于安慰剂组(1.1个月，0.95-1.68；风险比0.38,95% CI 0.31-0.48; p
Background Afatinib, an irreversible ErbB-family blocker, has shown preclinical activity when tested in EGFR mutant models with mutations that confer resistance to EGFR tyrosine-kinase inhibitors. We aimed to assess its efficacy in patients with advanced lung adenocarcinoma with previous treatment failure on EGFR tyrosine-kinase inhibitors.Methods In this phase 2b/3 trial, we enrolled patients with stage IIIB or IV adenocarcinoma and an Eastern Cooperative Oncology Group performance (ECOG) performance score of 0-2 who had received one or two previous chemotherapy regimens and had disease progression after at least 12 weeks of treatment with erlotinib or gefitinib. We used a computer-generated sequence to randomly allocate patients (2: 1) to either afatinib (50 mg per day) or placebo; all patients received best supportive care. Randomisation was done in blocks of three and was stratified by sex and baseline ECOG performance status (0-1 vs 2). Investigators, patients, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival (from date of randomisation to death), analysed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00656136.Findings Between May 26, 2008, and Sept 21, 2009, we identified 697 patients, 585 of whom were randomly allocated to treatment (390 to afatinib, 195 to placebo). Median overall survival was 10.8 months (95% CI 10.0-12.0) in the afatinib group and 12.0 months (10.2-14.3) in the placebo group (hazard ratio 1.08, 95% CI 0.86-1.35; p=0.74). Median progression-free survival was longer in the afatinib group (3.3 months, 95% CI 2.79-4.40) than it was in the placebo group (1.1 months, 0.95-1.68; hazard ratio 0.38, 95% CI 0.31-0.48; p