Programmed Death-Ligand 1 Immunohistochemistry Assay Comparison Studies in NSCLC: Characterization of the 73-10 Assay
Programmed Death-Ligand 1 Immunohistochemistry Assay Comparison Studies in NSCLC: Characterization of the 73-10 Assay
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DOI：
10.1016/j.jtho.2020.04.013
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发表时间：
2020-08-01
影响因子：
20.4
通讯作者：
Kerr, Keith M.
中科院分区：
文献类型：
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作者：
Grote, Hans Juergen;Feng, Zheng;Kerr, Keith M.
前言：在治疗性抗程序性细胞死亡蛋白1(抗PD-1)或PD-L1抗体的临床程序中，已经独立开发了几种程序性死亡配体1(PD-L1)免疫组织化学(IHC)分析方法，这使得有必要对检测结果的可比性进行评估。我们鉴定了在Avelumab(抗PD-L1)或bintrafusp alfa(M7824；双功能免疫疗法)临床试验中使用的DAKO PD-L1 IHC 73-10试验，并将其与DAKO PD-L1 IHC 22C3药物Dx试验进行比较，Dx试验被批准用于晚期NSCLC患者的Pembrolizumab单一治疗。在148例商业非小细胞肺癌标本中，73-10法染色大于或等于1%、大于或等于50%、大于或等于80%的肿瘤细胞分别为64.2%、36.5%和23.6%，而22C3法染色为大于或等于50%的肿瘤细胞占20.3%。在83个NSCLC临床试验样本中，73-10法染色大于或等于1%和大于或等于80%PD-L1+的样本分别占79.5%和31.3%，而22C3法染色大于或等于1%和大于或等于50%的Pd-L1+分别占59.0%和21.7%。Avelumab在大于或等于80%PD-L1+和大于等于50%PD-L1+界值的73-10和22C3亚组中的疗效相似，客观应答率分别为26.9%和33.3%。结论：73-10法对PD-L1染色具有很高的敏感性，在73-10法大于或等于80%的界值与22C3大于或等于50%的界值之间染色效果相当。(C)2020年国际肺癌研究协会。由爱思唯尔公司出版。
Introduction: Several programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays have been developed independently within clinical programs for therapeutic anti-programmed cell death protein 1 (anti-PD-1) or PD-L1 antibodies, necessitating assessment of assay comparability. We characterized the Dako PD-L1 IHC 73-10 assay used in clinical trials of avelumab (anti-PD-L1) or bintrafusp alfa (M7824; bifunctional immunotherapy) and compared it with the Dako PD-L1 IHC 22C3 pharmDx assay, an approved companion diagnostic for pembrolizumab monotherapy in patients with advanced NSCLC.Methods: Formalin-fixed, paraffin-embedded NSCLC tumor samples from a commercial source and from the JAVELIN Solid Tumor phase 1 trial of avelumab (NCT01772004) were stained using the 73-10 and 22C3 IHC assays with a standard protocol.Results: Both assays displayed expected PD-L1 staining patterns. In 148 commercial NSCLC samples, the 73-10 assay stained greater than or equal to 1%, greater than or equal to 50%, and greater than or equal to 80% of tumor cells as PD-L1+ in 64.2%, 36.5%, and 23.6% of the samples, respectively, whereas the 22C3 assay stained 20.3% of the samples as greater than or equal to 50% PD-L1+. In 83 NSCLC clinical trial samples, the 73-10 assay stained 79.5% and 31.3% of the samples as greater than or equal to 1% and greater than or equal to 80% PD-L1+, respectively, whereas the 22C3 assay stained 59.0% and 21.7% as greater than or equal to 1% and greater than or equal to 50% PD-L1+, respectively. Efficacy of avelumab was similar in the subgroups classified with the 73-10 and 22C3 assays using greater than or equal to 80% and greater than or equal to 50% PD-L1+ cutoffs, with objective response rates of 26.9% and 33.3%, respectively.Conclusions: The 73-10 assay demonstrated high sensitivity for PD-L1 staining, and staining was comparable between the greater than or equal to 80% cutoff of the 73-10 assay and greater than or equal to 50% cutoff of the 22C3 assay. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc.