Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, United Kingdom.
Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, United Kingdom.
Clin Cancer Res. 2017 Jul 15;23(14):3585-3591. doi: 10.1158/1078-0432.CCR-16-2375. Epub 2017 Jan 10.
Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized, and different assay methods could lead to inappropriate treatment selection. This study establishes the extent of concordance between three validated, commercially available PD-L1 IHC diagnostic assays for NSCLC patients [Ventana SP263 (durvalumab), Dako 22C3 (pembrolizumab), and Dako 28-8 (nivolumab)]. Five hundred formalin-fixed, paraffin-embedded archival NSCLC samples were obtained from commercial sources. Stained slides were read in batches on an assay-by-assay basis by a single pathologist trained in all methods, in a Clinical Laboratory Improvements Amendments program-certified laboratory. An additional pathologist performed an independent review of 200 stained samples for each assay. PD-L1 expression was evaluable with all assays in 493 samples. The three assays showed similar patterns of tumor membrane staining, with high correlation between percent PD-L1 staining. An overall percentage agreement of >90% was achieved between assays at multiple expression cutoffs, including 1%, 10%, 25%, and 50% tumor membrane staining. This study builds optimism that harmonization between assays may be possible, and that the three assays studied could potentially be used interchangeably to identify patients most likely to respond to anti-PD-1/PD-L1 immunotherapies, provided the appropriate clinically defined algorithm and agent are always linked. .
免疫疗法靶向程序性细胞死亡受体-1（PD-1）和程序性细胞死亡配体-1（PD-L1）在非小细胞肺癌（NSCLC）中显示出令人鼓舞的抗肿瘤活性和可管理的耐受性，尤其是在高肿瘤 PD-L1 表达的患者中，这些表达是通过针对单个药物开发的伴随或互补诊断检测来检测的。实验室不太可能使用多种检测平台。此外，商业上可用的诊断检测方法没有标准化，不同的检测方法可能导致不适当的治疗选择。本研究评估了三种经过验证的、商业上可用的 NSCLC 患者 PD-L1 IHC 诊断检测方法[Ventana SP263（度伐利尤单抗）、Dako 22C3（帕博利珠单抗）和 Dako 28-8（纳武利尤单抗）]之间的一致性程度。从商业来源获得了 500 例福尔马林固定、石蜡包埋的存档 NSCLC 样本。染色的幻灯片在一个临床实验室改进修正案计划认证的实验室中，由一名接受过所有方法培训的单一病理学家在逐个检测的基础上进行批处理读取。每个检测还由另一名病理学家对 200 个染色样本进行独立审查。所有检测均可评估 493 个样本中的 PD-L1 表达。三种检测均显示出相似的肿瘤膜染色模式，PD-L1 染色百分比之间具有高度相关性。在多个表达截止值下，包括 1%、10%、25%和 50%肿瘤膜染色，检测之间达到了>90%的总体百分比一致性。这项研究使人们乐观地认为，检测之间的协调是可能的，并且所研究的三种检测方法有可能相互替换，以识别最有可能对抗 PD-1/PD-L1 免疫疗法有反应的患者，前提是始终将适当的临床定义算法和药物联系起来。
