Shukuya Takehito, Carbone David P
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
J Thorac Oncol. 2016 Jul;11(7):976-88. doi: 10.1016/j.jtho.2016.02.015. Epub 2016 Mar 2.
Blockade of the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis using antibodies against the associated receptors and ligands has yielded good clinical responses and improved overall survival in patients with non-small cell lung cancer (NSCLC). Once patients show a response to anti-PD-1/PD-L1 antibody, the median duration of response is often longer than that achieved using existing cytotoxic agents and even some molecular targeted agents. However, the response rates to these antibodies are only 15% to 20% in unselected patients with NSCLC and the cost of this therapy is high. Therefore, there is an urgent need for effective predictive biomarkers to identify patients likely to benefit. PD-L1 expression, which can be detected by immunohistochemical analysis, is a rational biomarker for selecting responders to anti-PD-1/PD-L1 antibody treatments, and this selection method has been introduced into clinical practice. However, the response rate to anti-PD-1/PD-L1 antibody in PD-L1-expressing patients with NSCLC is only 15% to 45%, response can occur in PD-L1-negative patients, and predictability based on PD-L1 expression may differ between nonsquamous NSCLC and squamous cell NSCLC. In addition, the methods of immunohistochemical analysis and evaluation of its results differ for different anti-PD-1/PD-L1 agents. This article reviews the existing data on predictive markers for the efficacy of anti-PD-1/PD-L1 antibodies in NSCLC.
使用针对程序性死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）轴相关受体和配体的抗体进行阻断，已在非小细胞肺癌（NSCLC）患者中产生了良好的临床反应并改善了总生存期。一旦患者对抗PD-1/PD-L1抗体产生反应，反应的中位持续时间通常比使用现有的细胞毒性药物甚至一些分子靶向药物所达到的时间更长。然而，在未经选择的NSCLC患者中，这些抗体的反应率仅为15%至20%，并且这种治疗的成本很高。因此，迫切需要有效的预测生物标志物来识别可能受益的患者。通过免疫组织化学分析可检测到的PD-L1表达，是选择抗PD-1/PD-L1抗体治疗反应者的合理生物标志物，并且这种选择方法已被引入临床实践。然而，在PD-L1表达的NSCLC患者中，抗PD-1/PD-L1抗体的反应率仅为15%至45%，PD-L1阴性患者也可能出现反应，并且基于PD-L1表达的可预测性在非鳞状NSCLC和鳞状细胞NSCLC之间可能有所不同。此外，不同抗PD-1/PD-L1药物的免疫组织化学分析方法及其结果评估也有所不同。本文综述了关于NSCLC中抗PD-1/PD-L1抗体疗效预测标志物的现有数据。
