First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer
First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer
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DOI：
10.1056/nejmoa1408440
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发表时间：
2014-12-04
影响因子：
158.5
通讯作者：
Waqar, S.
中科院分区：
文献类型：
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作者：
Solomon, Benjamin J.;Mok, Tony;Waqar, S.
ALK抑制剂克唑替尼作为晚期ALK阳性非小细胞肺癌（NSCLC）一线治疗的疗效与标准化疗相比尚不清楚。METHODS我们进行了一项开放标签的3期临床试验，在343例晚期ALK阳性非鳞状NSCLC患者中比较克唑替尼与化疗，这些患者既往未接受过晚期疾病的系统治疗。患者被随机分配接受口服克唑替尼，剂量为250 mg，每日两次，或接受静脉化疗（培美曲塞，每平方米体表面积500 mg，加上顺铂，每平方米75 mg，或卡铂，目标曲线下面积）每3周接受一次，最多接受6个周期。毫升每分钟5至6毫克。允许接受化疗的患者在疾病进展后交叉至克唑替尼治疗。主要终点是通过独立的放射学检查评估的无进展生存期。结论克唑替尼组的无进展生存期显著长于化疗组（中位数，10.9个月vs. 7.0个月;克唑替尼组进展或死亡的风险比，0.45; 95%可信区间[CI]，0.35 - 0.60; P
BACKGROUNDThe efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown.METHODSWe conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease. Patients were randomly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy (pemetrexed, 500 mg per square meter of body-surface area, plus either cisplatin, 75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy. The primary end point was progression-free survival as assessed by independent radiologic review.RESULTSProgression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P