Development of a Companion Diagnostic for Pembrolizumab in Non-Small Cell Lung Cancer Using Immunohistochemistry for Programmed Death Ligand-1
Development of a Companion Diagnostic for Pembrolizumab in Non-Small Cell Lung Cancer Using Immunohistochemistry for Programmed Death Ligand-1
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DOI：
10.5858/arpa.2015-0542-oa
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发表时间：
2016-11-01
影响因子：
4.6
通讯作者：
Emancipator, Kenneth
中科院分区：
文献类型：
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作者：
Dolled-Filhart, Marisa;Roach, Charlotte;Emancipator, Kenneth
背景.-肿瘤表达的程序性死亡配体-1 (PD-L1) 可能使它们能够避免免疫监视。目的.-使用 Dako 平台上的 22C3 抗 PD-L1 鼠单克隆抗体开发一种 PD-L1 免疫组织化学检测方法，作为非小细胞肺癌患者帕博利珠单抗的可能伴随诊断。设计.-来自 146 名接受过治疗的非小细胞肺癌患者的肿瘤样本KEYNOTE-001 中的派姆单抗以及可用的反应数据由一位病理学家使用 4 种方法根据染色强度进行评分：任意强度染色的肿瘤细胞百分比 (PS1)、中/强强度 (PS2)、强强度 (PS3) 和 H 评分 (PS1 + PS2 + PS3)。使用受试者操作特征分析确定预测派姆单抗反应的截止分数。根据实体瘤疗效评估标准 1.1 版 (n = 146)，对患有可测量疾病的患者进行无进展生存期和总生存期评估。结果 - 评估的 4 种评分方法表现相似；截止分数为 50% 的 PS1 是实践中最简单、最容易实施的方法。在 PS1 评分为 50% 或更高的 44 名患者中，有 19 名 (43%) 观察到对派姆单抗的反应，在 PS1 低于 50% 的 102 名患者中，有 8 名 (8%) 观察到对派姆单抗的反应（比值比，8.93）。 PS1 等于或高于 50% 的患者的中位无进展生存期和总生存期尚未达到，而 PS1 低于 50% 的患者的中位无进展生存期和总生存期分别为 2.1 个月和 6.1 个月。结论：PD-L1 免疫组织化学检测显示了丰富试验人群和作为非小细胞肺癌伴随诊断工具的潜力。
Context.-Programmed death ligand-1 (PD-L1) expression by tumors may enable them to avoid immunosurveillance.Objective.-To develop a PD-L1 immunohistochemical assay using the 22C3 anti-PD-L1 murine monoclonal antibody on the Dako platform as a possible companion diagnostic for pembrolizumab in patients with non-small cell lung cancer.Design.-Tumor samples from 146 patients with non-small cell lung cancer treated with pembrolizumab in KEYNOTE-001 and for whom response data were available were scored according to their staining intensity by a single pathologist using 4 methods: percentage of tumor cells staining at any intensity (PS1), moderate/strong intensity (PS2), strong intensity (PS3), and H-score (PS1 + PS2 + PS3). The cutoff score for predicting response to pembrolizumab was determined using receiver operating characteristic analysis. Progression-free and overall survival were assessed in patients with measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (n = 146).Results.-The 4 scoring methods assessed performed similarly; PS1 with a 50% cutoff score is the simplest and easiest method to implement in practice. Response to pembrolizumab was observed in 19 of 44 patients (43%) with a PS1 score of 50% or higher and 8 of 102 patients (8%) with PS1 lower than 50% (odds ratio, 8.93). Median progression-free and overall survival was 4.0 months and not yet reached, respectively, for patients with a PS1 of 50% or higher, and 2.1 and 6.1 months, respectively, for those with PS1 lower than 50%.Conclusion.-The PD-L1 immunohistochemical assay shows the potential for enrichment of trial populations and as a companion diagnostic tool in non-small cell lung cancer.