PD-L1 表达对胆道癌抗 PD-1/PD-L1 治疗反应的预测价值：系统评价和荟萃分析。

The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis.

机构信息

Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea.

出版信息

Front Immunol. 2024 Mar 28;15:1321813. doi: 10.3389/fimmu.2024.1321813. eCollection 2024.

DOI:10.3389/fimmu.2024.1321813

PMID:38605964

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11007040/

Abstract

BACKGROUND

Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy.

METHODS

We conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity.

RESULTS

A total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 PD-L1), presence of additional intervention (monotherapy combination therapy), and PD-L1 cut-off level (1% ≥5%) significantly affected the predictive value of PD-L1 expression.

CONCLUSION

PD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.

摘要

背景

最近，抗程序性细胞死亡蛋白 1（PD-1）/程序性死亡配体 1（PD-L1）免疫疗法为晚期胆道癌（BTC）患者带来了有希望的结果。然而，患者对治疗的反应存在高度异质性，并且缺乏预测性生物标志物。我们进行了一项系统评价和荟萃分析，以评估 PD-L1 表达作为 BTC 患者接受抗 PD-1/PD-L1 治疗的治疗反应和生存的潜在生物标志物。

方法

我们通过 PubMed、EMBASE 和 Cochrane Library 数据库进行了全面的系统文献检索，检索时间截至 2023 年 6 月。主要结局指标包括根据 PD-L1 表达评估的客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。进行了亚组分析和荟萃回归分析，以确定可能的异质性来源。

结果

最终分析共纳入 30 项研究。汇总分析显示，PD-L1（+）和 PD-L1（-）患者之间的 ORR（比值比 [OR]，1.56；95%置信区间 [CI]，0.94-2.56）和 DCR（OR，1.84；95%CI，0.88-3.82）无显著差异。相比之下，PD-L1（+）患者的 PFS（风险比 [HR]，0.54，95%CI，0.41-0.71）和 OS（HR，0.58；95%CI，0.47-0.72）均优于 PD-L1（-）患者。排除回顾性研究的敏感性分析结果与主要结果无显著差异。此外，荟萃回归表明，药物靶点（PD-1/PD-L1）、是否存在其他干预（单药治疗/联合治疗）以及 PD-L1 截断值（1%/≥5%）显著影响 PD-L1 表达的预测价值。