A Comprehensive Analysis of Programmed Cell Death Ligand-1 Expression With the Clone SP142 Antibody in Non–Small-Cell Lung Cancer Patients

医学 肺癌 阿替唑单抗 免疫组织化学 肿瘤科 克隆(Java方法) 免疫疗法 切断 单变量分析 癌症 内科学 癌症研究 病理 多元分析 无容量 生物 基因 物理 量子力学 生物化学
作者
Kazuki Takada,Gouji Toyokawa,Tatsuro Okamoto,Mototsugu Shimokawa,Yuka Kozuma,Taichi Matsubara,Naoki Haratake,Takaki Akamine,Shinkichi Takamori,Masakazu Katsura,Shoji Fukushima,Yoshinao Oda,Yoshihiko Maehara
出处
期刊:Clinical Lung Cancer [Elsevier]
卷期号:18 (5): 572-582.e1 被引量:47
标识
DOI:10.1016/j.cllc.2017.02.004
摘要

Background Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with anti–PD-1 therapy currently the standard treatment for non–small-cell lung cancer (NSCLC) patients after the failure of first-line chemotherapy treatment. The recent phase II POPLAR and phase III OAK studies showed that atezolizumab, a representative PD-L1 inhibitor, exhibited a survival benefit compared with standard therapy in patients with NSCLC. Patients and Methods We examined PD-L1 expression in NSCLC using the clone SP142 of POPLAR and OAK studies. PD-L1 expression in 499 surgically resected NSCLC patients was evaluated using immunohistochemistry using SP142. We set cutoff values as 1%, 5%, 10%, and 50%. Results The samples from 189 (37.9%), 119 (23.8%), 71 (14.2%), and 39 (7.8%) patients were positive for PD-L1 expression at cutoff values of 1%, 5%, 10%, and 50%, respectively. Fisher exact tests showed that PD-L1 positivity was significantly associated with male sex, smoking, advanced stage, the presence of vascular invasion, squamous cell carcinoma, and wild type epidermal growth factor receptor gene mutation status at all cutoff values. Univariate and multivariate survival analyses revealed that PD–L1-positive patients had a worse prognosis than PD–L1-negative patients only at the 1% cutoff value. Forest plot analyses showed that the 1% cutoff provided a more sensitive value for the prediction of postoperative prognosis. Conclusion PD-L1 expression varied greatly according to different cutoff values. This study might be a useful reference to understand the results of POPLAR and OAK studies and to select patients likely to benefit from atezolizumab.
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