First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study
First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study
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DOI：
10.1016/s0140-6736(17)30123-x
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发表时间：
2017-03-04
期刊：
影响因子：
168.9
通讯作者：
de Castro, Gilberto, Jr.
中科院分区：
文献类型：
--
作者：
Soria, Jean-Charles;Tan, Daniel S. W.;de Castro, Gilberto, Jr.
背景西瑞替尼治疗未经治疗的间变性淋巴瘤激酶（ALK）重排非小细胞肺癌（NSCLC）的疗效尚不清楚。我们在这些患者中评估了西瑞替尼与铂基化疗的疗效和安全性。这项随机、开放标签的3期研究在28个国家的134个中心进行，研究对象是未经治疗的IIIB/IV期alk重排非鳞状NSCLC患者。符合条件的患者通过交互反应技术被分配到口服塞瑞替尼750 mg/天或铂基化疗([顺铂75 mg/m（2)或卡铂AUC 5-6加培美曲塞500 mg/m(2)]，每3周4个周期，随后维持培美曲塞）；根据世界卫生组织的表现状况（0 vs 1-2）、既往新辅助或辅助化疗以及筛查时研究者评估的脑转移是否存在，对随机分组进行分层。研究人员和患者没有被掩盖治疗分配。主要终点是盲法独立审查委员会评估的无进展生存期，基于所有随机分配的患者（完整分析集）。基于完整的分析集进行疗效分析。所有的安全性分析都是基于安全集进行的，其中包括所有接受至少一剂研究药物的患者。该试验已在ClinicalTrials.gov注册，注册号为NCT01828099。在2013年8月19日至2015年5月11日期间，376名患者被随机分配到ceritinib （n=189）或化疗（n=187）组。经盲法独立审查委员会评估的中位无进展生存期（ceritinib组）为16.6个月（95% CI 12.6-27.2），化疗组为8.1个月（5.8-11.1）(风险比0.55 [95% CI 0.42-0.73]
Background The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is not known. We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients.Methods This randomised, open-label, phase 3 study in untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC was done in 134 centres across 28 countries. Eligible patients were assigned via interactive response technology to oral ceritinib 750 mg/day or platinum-based chemotherapy ([cisplatin 75 mg/m(2) or carboplatin AUC 5-6 plus pemetrexed 500 mg/m(2)] every 3 weeks for four cycles followed by maintenance pemetrexed); randomisation was stratified by World Health Organization performance status (0 vs 1-2), previous neoadjuvant or adjuvant chemotherapy, and presence of brain metastases as per investigator's assessment at screening. Investigators and patients were not masked to treatment assignment. The primary endpoint was blinded independent review committee assessed progression-free survival, based on all randomly assigned patients (the full analysis set). Efficacy analyses were done based on the full analysis set. All safety analyses were done based on the safety set, which included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01828099.Findings Between Aug 19, 2013, and May 11, 2015, 376 patients were randomly assigned to ceritinib (n=189) or chemotherapy (n=187). Median progression-free survival (as assessed by blinded independent review committee) was 16.6 months (95% CI 12.6-27.2) in the ceritinib group and 8.1 months (5.8-11.1) in the chemotherapy group (hazard ratio 0.55 [95% CI 0.42-0.73]; p