Performance of the Food and Drug Administration/EMA-approved programmed cell death ligand-1 assays in urothelial carcinoma with emphasis on therapy stratification for first-line use of atezolizumab and pembrolizumab
Performance of the Food and Drug Administration/EMA-approved programmed cell death ligand-1 assays in urothelial carcinoma with emphasis on therapy stratification for first-line use of atezolizumab and pembrolizumab
复制标题
DOI：
10.1016/j.ejca.2018.11.007
复制
发表时间：
2019-01-01
影响因子：
8.4
通讯作者：
Erlmeier, Franziska
中科院分区：
文献类型：
--
作者：
Eckstein, Markus;Erben, Philipp;Erlmeier, Franziska
背景：最近，美国食品和药物管理局(FDA)/欧洲药品管理局(EMA)通过定义不同的程序性细胞死亡配体-1截止点，限制了阿替唑单抗和培溴利珠单抗在转移性尿路上皮癌患者中的一线使用。我们分析了所有FDA/EMA批准的程序性细胞死亡配体-1检测的诊断性能，重点是阿替唑单抗和培溴利珠单抗一线治疗的新限制。患者和方法：在组织芯片上分析251例尿路上皮癌，每个肿瘤有四个核心。染色是在认证的实验室中进行的，使用的是Ventana Benchmark Ultra和DAKO LINK 48台自动染色设备。染色由两名训练有素的病理学家逐个化验。总体同意百分比(OPA)是在预设的截止点上计算的。通过不同的评分算法计算阳性符合率(PPA)和阴性符合率(NPA)。结果：DAKO 28-8、22C3和Ventana SP263具有高度的批间相关性(r范围为0.83-0.91)。Ventana SP142与其他三种检测方法的批间相关性为中等(r范围为0.66-0.75)。DAKO 28-8、22C3和Ventana SP263检测的OPA为93.3%。包括SP142在内的OPA为84.1%。在DAKO 28-8、22C3和SP263检测中，不同计分算法的混合PPA和NPA分别为89.4%和95.3%。用SP142检测，聚合的PPA为59.1%。SP142检测确定较少的合格患者接受阿替唑珠单抗/培溴珠单抗一线治疗。结论：DAKO 28-8、22C3和SP263检测具有互换性能。SP142检测显示出不同的染色结果。试验间的变异性导致使用阿泰唑单抗和培溴利珠单抗一线治疗的合格患者的检测率不同。(C)2018爱思唯尔有限公司。保留所有权利。
Background: Recently, the Food and Drug Administration (FDA)/European Medicines Agency (EMA) restricted first-line use of atezolizumab and pembrolizumab in patients with metastasised urothelial carcinoma by defining distinct programmed cell death ligand-1 cut-offs. We analysed the diagnostic performance of all FDA/EMA-approved programmed cell death ligand-1 assays with emphasis on new restrictions for first-line treatment with atezolizumab and pembrolizumab.Patients and methods: Two hundred fifty-one urothelial carcinomas were analysed on tissue microarrays with four cores of each tumour. Stains were performed in certified laboratories on Ventana Benchmark Ultra and Dako Link 48 autostainers. Stains were read on an assay-by-assay basis by two trained pathologists. Overall percentage agreement (OPA) was calculated across the preset cut-offs. Positive percentage agreement (PPA) and negative percentage agreement (NPA) were calculated across different scoring algorithms. Venn diagrams were constructed to illustrate discordance according to the recent FDA/EMA guidelines.Results: The Dako 28-8, 22c3 and the Ventana SP263 assays showed high interassay correlation (r-range 0.83-0.91). Interassay correlation between the Ventana SP142 and the three other assays was moderate (r-range 0.66-0.75). OPA of 93.3% was achieved between the Dako 28-8, 22c3 and Ventana SP263 assays. OPA including the SP142 was 84.1%. Pooled PPA and NPA of different scoring algorithms was 89.4% and 95.3% for the Dako 28-8, 22c3 and the SP263 assays, respectively. With the SP142 assay, pooled PPA was 59.1%. The SP142 assay identifies fewer eligible patients for first-line treatment with atezolizumab/pembrolizumab.Conclusion: Dako 28-8, 22c3 and SP263 assays show interchangeable performance. The SP142 assay shows divergent staining results. Interassay variability leads to different detection rates of eligible patients for first-line treatment with atezolizumab and pembrolizumab. (C) 2018 Elsevier Ltd. All rights reserved.