Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer
Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer
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DOI：
10.1056/nejmoa1214886
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发表时间：
2013-06-20
影响因子：
158.5
通讯作者：
Jaenne, Pasi A.
中科院分区：
文献类型：
--
作者：
Shaw, Alice T.;Kim, Dong-Wan;Jaenne, Pasi A.
背景：在单组研究中，间变性淋巴瘤激酶基因（ALK）的染色体重排与克唑替尼（一种针对ALK的口服酪氨酸激酶抑制剂）的显著临床反应相关。克里唑替尼在疗效方面是否优于标准化疗尚不清楚。方法：我们进行了一项3期开放标签试验，比较了347例局部晚期或转移性alk阳性肺癌患者的克里唑替尼与化疗，这些患者先前接受过一种基于铂的方案。患者被随机分配接受克唑替尼（250毫克）口服治疗，每日两次，或静脉化疗培美曲塞（500毫克/平方米体表面积）或多西他赛（75毫克/平方米）每3周。在另一项单独的研究中，化疗组中有疾病进展的患者被允许使用克唑替尼。主要终点为无进展生存期。结果克唑替尼组的中位无进展生存期为7.7个月，化疗组的中位无进展生存期为3.0个月(克唑替尼进展或死亡的危险比为0.49；95%可信区间[CI]， 0.37 ~ 0.64
BackgroundIn single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown.MethodsWe conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival.ResultsThe median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P