Center of Predictive Molecular Medicine, Center for Excellence on Aging and Translational Medicine, University of Chieti-Pescara, Chieti, Italy.
Division of Pathology, European Institute of Oncology, Milan, Italy.
J Thorac Oncol. 2017 Nov;12(11):1654-1663. doi: 10.1016/j.jtho.2017.07.031. Epub 2017 Aug 14.
Among the several agents targeting the programmed cell death 1 (PD-1) pathway, pembrolizumab is currently the only one approved for the treatment of patients with NSCLC in association with a companion diagnostic assay, the anti-PD-L1 immunohistochemical (IHC) 22C3 PharmDx (Agilent Technologies, Santa Clara, CA) using the Dako Autostainer (Dako, Carpinteria, CA). However, the Dako platform is not present in each pathology department, and this technical limitation is a major problem for the diffusion of the PD-L1 IHC predictive test for pembrolizumab.
The Italian Society of Anatomic Pathology and Cytopathology and the Italian Association of Medical Oncology in an independent, multicenter study compared the in vitro diagnostics PD-L1 IHC 22C3 pharmDx test (Agilent) on the Dako Autostainer and the in vitro diagnostics Ventana PD-L1 (SP263) test on the Ventana BenchMark platform (Ventana Medical Systems, Tucson, AZ). Using serial sections from tissue microarrays, 100 lung adenocarcinomas were locally stained and scored in four centers with the same antibody batches.
A high analytical correlation (more than 90% at the lower 95% confidence interval [CI] value) between PD-L1 expression levels obtained with the 22C3 and SP263 assays was observed. At the proposed clinically relevant cutoffs (≥50% and ≥1%), the overall concordances between 22C3 and SP263 data were 0.99 (95% CI: 0.96-1) and 0.80 (95% CI: 0.68-0.91), respectively. The lower agreement between data obtained with the 22C3 and SP263 clones at the cutoff of 1% or higher was mainly related to the lower (about 80%) interrater agreement at this cutoff with each clone.
These results indicate a high correlation between PD-L1 IHC expression data obtained with the Agilent PD-L1 IHC 22C3 pharmDx and the Ventana PD-L1 (SP263) tests in NSCLC and suggest that the two assays could be utilized interchangeably as an aid to select patients for first-line and second-line treatment with pembrolizumab and potentially with other anti-PD-1/PD-L1 checkpoint inhibitors.
在几种针对程序性细胞死亡 1 (PD-1) 通路的药物中，pembrolizumab 是目前唯一一种与伴随诊断检测试剂（抗 PD-L1 免疫组化（IHC）22C3 PharmDx（Agilent Technologies，Santa Clara，CA））联合使用，用于治疗非小细胞肺癌（NSCLC）患者的药物，该检测试剂采用 Dako Autostainer（Dako，Carpinteria，CA）。然而，并非每个病理科都配备有 Dako 平台，这一技术限制极大地阻碍了 pembrolizumab 的 PD-L1 IHC 预测性检测的推广。
意大利解剖病理学协会和意大利医学肿瘤学协会在一项独立的多中心研究中，比较了 Agilent 的 PD-L1 IHC 22C3 pharmDx 检测试剂（Dako Autostainer）和 Ventana Medical Systems（Tucson，AZ）的 Ventana PD-L1（SP263）检测试剂在体外诊断中的应用。使用组织微阵列的连续切片，在四个中心用相同的抗体批次对 100 例肺腺癌进行局部染色和评分。
22C3 和 SP263 检测试剂得到的 PD-L1 表达水平具有高度的分析相关性（置信区间[CI]低值大于 90%）。在建议的临床相关截止值（≥50%和≥1%）下，22C3 和 SP263 数据之间的总体一致性分别为 0.99（95%CI：0.96-1）和 0.80（95%CI：0.68-0.91）。在 1%或更高的截止值下，22C3 和 SP263 检测试剂得到的数据之间的一致性较低，主要是由于每个检测试剂在该截止值下的组内一致性较低（约 80%）。
这些结果表明，在非小细胞肺癌中，Agilent PD-L1 IHC 22C3 pharmDx 和 Ventana PD-L1（SP263）检测试剂得到的 PD-L1 IHC 表达数据之间具有高度相关性，并表明这两种检测试剂可以相互替代，作为选择患者接受一线和二线 pembrolizumab 及潜在其他抗 PD-1/PD-L1 检查点抑制剂治疗的辅助手段。
