Lantuejoul Sylvie, Damiola Francesca, Adam Julien
Département de Biopathologie et Département de la Recherche Translationnelle et de l'Innovation, Centre Léon Bérard Unicancer, Lyon, France.
Université Grenoble Alpes, Grenoble, France.
Transl Lung Cancer Res. 2020 Jun;9(3):906-916. doi: 10.21037/tlcr.2020.03.23.
Immune checkpoint inhibitors (ICI) including programmed death 1 (PD-1) inhibitors, such as nivolumab and pembrolizumab, or programmed death ligand 1 (PD-L1) inhibitors, such as atezolizumab and durvalumab, have recently emerged in advanced stage lung cancer as new standards of care. They are now indicated in first- line and second- or later-line treatment of metastatic or locally-advanced stage III non-small cell lung cancer (NSCLC), as well as for metastatic small cell lung cancer (SCLC), as single agent immunotherapy or in combination with chemotherapy. Four PD-L1 immunohistochemistry (IHC) assays have been established and validated in randomized trials, each for a specific ICI. They use different primary monoclonal antibodies, platforms and detection systems, as well as different scoring systems to assess PD-L1 expression either by tumor cells (TCs) and/or by infiltrating immune cells (ICs). Most studies have shown a close analytical performance of three of these clinically-validated standardized assays, but their use restricted to dedicated platforms, which are not all available in most laboratories, questions their applicability. In addition, the relative high costs of the assays have led to the development of in-house protocols in many pathology laboratories. Their use in clinical practice to assess the predictive value of PD-L1 expression for prescription of ICI raises the issue of their reliability and their validation as compared to standardized assays. This article discusses the main comparative studies available between LDT and assays, with clear evidence that LDT can reach a performance equivalent to the trial-validated assays. The requirements are an adequate validation as compared to an appropriate standard, and the participation to external quality assurance programs and training programs for PD-L1 IHC assessment for pathologists.
免疫检查点抑制剂（ICI），包括程序性死亡蛋白1（PD-1）抑制剂，如纳武利尤单抗和帕博利珠单抗，或程序性死亡配体1（PD-L1）抑制剂，如阿特珠单抗和度伐利尤单抗，最近已成为晚期肺癌治疗的新标准。它们目前被用于转移性或局部晚期III期非小细胞肺癌（NSCLC）的一线和二线或后续治疗，以及转移性小细胞肺癌（SCLC），作为单药免疫疗法或与化疗联合使用。四种PD-L1免疫组织化学（IHC）检测方法已在随机试验中建立并验证，每种方法对应一种特定的ICI。它们使用不同的一抗单克隆抗体、平台和检测系统，以及不同的评分系统来评估肿瘤细胞（TCs）和/或浸润免疫细胞（ICs）的PD-L1表达。大多数研究表明，这三种经过临床验证的标准化检测方法具有相近的分析性能，但它们仅限于特定的平台使用，而大多数实验室并非都具备这些平台，这对它们的适用性提出了质疑。此外，检测方法相对较高的成本促使许多病理实验室开发内部方案。在临床实践中使用这些方法来评估PD-L1表达对ICI处方的预测价值，引发了与标准化检测方法相比其可靠性和验证的问题。本文讨论了实验室自建检测方法（LDT）与标准化检测方法之间的主要比较研究，有明确证据表明LDT可以达到与试验验证检测方法相当的性能。要求是与适当的标准相比进行充分的验证，并参与外部质量保证计划以及针对病理学家的PD-L1 IHC评估培训计划。
