Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial
Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial
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DOI：
10.1016/s0140-6736(16)00587-0
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发表时间：
2016-04-30
期刊：
影响因子：
168.9
通讯作者：
Rittmeyer, Achim
中科院分区：
文献类型：
--
作者：
Fehrenbacher, Louis;Spira, Alexander;Rittmeyer, Achim
背景：既往治疗过的晚期或转移性非小细胞肺癌(NSCLC)患者的预后很差。抗程序性死亡配体1(PD-L1)抗体在临床上具有抗肿瘤活性，包括非小细胞肺癌，特别是肿瘤细胞和/或肿瘤浸润性免疫细胞上表达PD-L1的癌症。我们通过肿瘤细胞和肿瘤浸润性免疫细胞上PD-L1的表达水平以及意向治疗人群中的分析，评估了阿替唑单抗与多西紫杉醇在先前治疗的NSCLC中的有效性和安全性。方法在这项开放的第二阶段随机对照试验中，在欧洲和北美13个国家的61个学术医学中心和社区肿瘤学实践中招募了在铂化疗后进展的NSCLC患者。主要纳入标准是东方合作肿瘤学小组表现状态0或1，实体肿瘤1.1版(RECIST v1.1)的反应评估标准可测量的疾病，以及足够的血液学和末端器官功能。患者根据PD-L1肿瘤浸润性免疫细胞状态、组织学和以前的治疗路线进行分层，并按置换区组随机(1：1，区组大小为4)随机分配(1：1)，使用交互式语音或网络系统接受静脉注射阿替唑单抗1200 mg或多西紫杉醇75 mg/m(2)，每3周一次。用免疫组织化学方法对肿瘤细胞中PD-L1的基础表达进行评分(肿瘤细胞表达PD-L1的百分比分别为TC3和TC2=5%和=1%和=5%和=1%和
Background Outcomes are poor for patients with previously treated, advanced or metastatic non-small-cell lung cancer (NSCLC). The anti-programmed death ligand 1 (PD-L1) antibody atezolizumab is clinically active against cancer, including NSCLC, especially cancers expressing PD-L1 on tumour cells, tumour-infiltrating immune cells, or both. We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC, analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population.Methods In this open-label, phase 2 randomised controlled trial, patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practices across 13 countries in Europe and North America. Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), and adequate haematological and end-organ function. Patients were stratified by PD-L1 tumour-infiltrating immune cell status, histology, and previous lines of therapy, and randomly assigned (1: 1) by permuted block randomisation (with a block size of four) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2) once every 3 weeks. Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells (as percentage of PD-L1-expressing tumour cells TC3 >= 50%, TC2 >= 5% and = 1% and = 5% and = 1% and