Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer
Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer
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DOI：
10.1056/nejmoa1704795
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发表时间：
2017-08-31
影响因子：
158.5
通讯作者：
Mok, Tony
中科院分区：
文献类型：
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作者：
Peters, Solange;Camidge, D. Ross;Mok, Tony
Alectinib是一种高度选择性的间变性淋巴瘤激酶（ALK）抑制剂，在治疗ALK阳性非小细胞肺癌（NSCLC）中显示出全身和中枢神经系统（CNS）疗效。我们调查阿来替尼与克唑替尼相比，在以前未经治疗的，先进的ALK阳性NSCLC患者，包括那些无症状的CNS diseases.METHODSIn一项随机，开放标签，3期试验，我们随机分配303例以前未经治疗的，先进的ALK阳性NSCLC患者接受阿来替尼（600毫克，每日两次）或克唑替尼（250毫克，每日两次）。主要终点是研究者评估的无进展生存期。次要终点是独立审查委员会评估的无进展生存期、CNS进展时间、客观缓解率和总生存期。（克唑替尼）和18.6个月（阿来替尼），Alectinib组62/152例患者（41%）和102/151例患者（68%）发生疾病进展或死亡事件克唑替尼组。阿来替尼治疗组经评估的无进展生存率显著高于克唑替尼治疗组（12个月无事件生存率，阿来替尼组为68.4% [95%置信区间（CI），61.0 - 75.9]，克唑替尼组为48.7% [95% CI，40.4 - 56.9];疾病进展或死亡的风险比，0.47 [95% CI，0.34 - 0.65]; P
BACKGROUNDAlectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease.METHODSIn a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival.RESULTSDuring a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P