肿瘤细胞和免疫细胞对作为转移性三阴性乳腺癌预测性生物标记物的 PD-L1 表达的贡献:来自 KEYNOTE-119 的探索性分析

IF 3.4 2区 医学 Q1 PATHOLOGY
Javier Cortes, Eric P Winer, Oleg Lipatov, Seock-Ah Im, Anthony Gonçalves, Eva Muñoz-Couselo, Keun Seok Lee, Peter Schmid, Kenji Tamura, Laura Testa, Isabell Witzel, Shoichiro Ohtani, Stephanie Hund, Karina Kulangara, Vassiliki Karantza, Jaime A Mejia, Junshui Ma, Petar Jelinic, Lingkang Huang, Scott K Pruitt, Kenneth Emancipator
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引用次数: 0

摘要

在3期KEYNOTE-119研究中,在既往接受过治疗的转移性三阴性乳腺癌(mTNBC)患者中,随着程序性死亡配体1(PD-L1)表达量的增加,pembrolizumab单药与化疗相比的疗效也会增加,其量化指标为联合阳性评分(CPS;PD-L1在肿瘤细胞和免疫细胞上的表达量)。这项探索性分析旨在确定肿瘤细胞中 PD-L1 的表达是否有助于 PD-L1 CPS 在 mTNBC 中的预测价值。使用 PD-L1 IHC 22C3 pharmDx 评估肿瘤样本中的 PD-L1 表达,并使用 CPS 和肿瘤比例评分(TPS;仅肿瘤细胞上的 PD-L1 表达)进行量化。计算的免疫细胞密度(CID)定义为 CPS 减 TPS。评估了每种评分方法(CPS、TPS和CID)预测使用pembrolizumab的临床结果的能力。使用 Pembrolizumab 时,CPS 的接收器操作特征曲线下面积为 0.69(95% CI = 0.58-0.80),TPS 为 0.55(95% CI = 0.46-0.64),CID 为 0.67(95% CI = 0.56-0.77)。校正截断流行率后,CPS 在预测客观反应率、无进展生存期和总生存期方面的表现与 CID 相当,甚至更好。这项探索性分析的数据表明,虽然免疫细胞上的 PD-L1 表达本身就能预测 mTNBC 对程序性死亡 1 阻断剂的反应,但增加肿瘤 PD-L1 表达评估(即 CPS,结合了免疫细胞和肿瘤细胞的 PD-L1 表达)可能会提高预测效果。因此,PD-L1 CPS仍是一种有效且广泛适用的统一评分系统,可用于丰富pembrolizumab对mTNBC和其他肿瘤类型的程序性死亡1阻断治疗的反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Contribution of tumour and immune cells to PD-L1 expression as a predictive biomarker in metastatic triple-negative breast cancer: exploratory analysis from KEYNOTE-119

Contribution of tumour and immune cells to PD-L1 expression as a predictive biomarker in metastatic triple-negative breast cancer: exploratory analysis from KEYNOTE-119

The efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD-L1) expression, as quantified by combined positive score (CPS; PD-L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple-negative breast cancer (mTNBC) in the phase 3 KEYNOTE-119 study. This exploratory analysis was conducted to determine whether the expression of PD-L1 on tumour cells contributes to the predictive value of PD-L1 CPS in mTNBC. PD-L1 expression in tumour samples was assessed using PD-L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD-L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58–0.80) for CPS, 0.55 (95% CI = 0.46–0.64) for TPS, and 0.67 (95% CI = 0.56–0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression-free survival, and overall survival. Data from this exploratory analysis suggest that, although PD-L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD-L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD-L1 expression) may improve prediction. PD-L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types.

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来源期刊
Journal of Pathology Clinical Research
Journal of Pathology Clinical Research Medicine-Pathology and Forensic Medicine
CiteScore
7.40
自引率
2.40%
发文量
47
审稿时长
20 weeks
期刊介绍: The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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