Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer
Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer
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DOI：
10.1056/nejmoa1501824
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发表时间：
2015-05-21
影响因子：
158.5
通讯作者：
Gandhi, Leena
中科院分区：
文献类型：
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作者：
Garon, Edward B.;Rizvi, Naiyer A.;Gandhi, Leena
背景：我们评估了pembrolizumab抑制晚期非小细胞肺癌患者程序性细胞死亡1 （PD-1）的有效性和安全性。我们还试图定义和验证与临床获益可能性相关的PD-1配体1 （PD-L1）的表达水平。方法：我们将495名接受派姆单抗治疗的患者（剂量为每3周每公斤体重2mg或10mg或每2周每公斤10mg）分配到训练组（182名患者）或验证组（313名患者）。我们使用免疫组织化学分析评估肿瘤样本中PD-L1的表达，结果报告为膜性PD-L1染色的肿瘤细胞的百分比（比例评分）。每9周进行一次中央评价。结果派姆单抗的常见副作用是疲劳、瘙痒和食欲下降，剂量或方案无明显差异。客观缓解率为19.4%，中位缓解持续时间为12.5个月。无进展生存期中位数为3.7个月，总生存期中位数为12.0个月。在至少50%的肿瘤细胞中PD-L1的表达被选择作为训练组的分界线。验证组中比例评分≥50%的患者，有效率为45.2%。在所有比例评分至少为50%的患者中，中位无进展生存期为6.3个月；中位总生存期未达到。结论spembrolizumab具有可接受的副作用，并且在晚期非小细胞肺癌患者中显示出抗肿瘤活性。PD-L1在至少50%的肿瘤细胞中的表达与派姆单抗疗效的提高相关。
BACKGROUNDWe assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit.METHODSWe assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review.RESULTSCommon side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached.CONCLUSIONSPembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab.