胃癌免疫治疗的合适程序性死亡受体 1 配体（PD-L1）临界值：一项系统评价与荟萃分析

Appropriate PD-L1 Cutoff Value for Gastric Cancer Immunotherapy: A Systematic Review and Meta-Analysis.

作者信息

Xie Tong, Zhang Zhening, Zhang Xiaotian, Qi Changsong, Shen Lin, Peng Zhi

机构信息

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.

出版信息

Front Oncol. 2021 Sep 1;11:646355. doi: 10.3389/fonc.2021.646355. eCollection 2021.

BACKGROUND

Immunotherapy dramatically changed the treatment landscape of gastric cancer in recent years. PD-L1 expression was proposed as a biomarker; however, the treatment strategy according to PD-L1 is still uncertain. Here, we aimed to find the appropriate cutoff value of PD-L1 expression for gastric cancer immunotherapy.

METHODS

We did a systematic electronic research of prospective clinical trials of gastric cancer immunotherapy across databases. Studies that provided subgroup analysis results stratified by PD-L1 expression were included. Objective response rate (ORR), disease control rate (DCR), hazard ratio (HR), and 95% confidential interval (CI) of progression-free survival (PFS) and overall survival (OS) at different PD-L1 cutoff values were extracted.

RESULTS

Twelve studies and 6,488 patients in total were finally included for pooled analysis. ORR in allover, PD-L1-negative, combined positive score (CPS) ≥1, CPS ≥5, and CPS ≥10 population was 10%, 3%, 13%, 20%, and 23%, respectively. Immune checkpoint inhibitor (ICI) monotherapy failed to show survival advantage in allover and PD-L1-negative patients. Single-agent ICI therapy prolonged OS (HR = 0.84, 95% CI: 0.74-0.96) but not PFS (HR = 1.38, 95% CI: 0.91-2.09) in PD-L1 CPS ≥1 patients. For combined immunotherapy, ORR in allover, PD-L1-negative, CPS ≥1, CPS ≥5, and CPS ≥10 population was 64%, 57%, 48%, 60%, and 58%, respectively. Allover population could gain survival benefit from combined immunotherapy based on the results from Checkmate-649. OS (HR = 0.81, 95% CI: 0.71-0.92) and PFS (HR = 0.77, 95% CI: 0.69-0.86) were significantly prolonged in PD-L1 CPS ≥1 patients receiving combined immunotherapy.

CONCLUSION

Efficacy and survival advantages improved with PD-L1 CPS. CPS ≥1 was the cutoff value for ICI monotherapy to gain survival benefit. Combined immunotherapy prolonged PFS and OS in allover population but needs further study to confirm it.

背景

近年来，免疫疗法极大地改变了胃癌的治疗格局。PD-L1表达被提议作为一种生物标志物；然而，根据PD-L1的治疗策略仍不确定。在此，我们旨在找到胃癌免疫治疗中PD-L1表达的合适临界值。

方法

我们对各数据库中胃癌免疫治疗的前瞻性临床试验进行了系统的电子检索。纳入提供按PD-L1表达分层的亚组分析结果的研究。提取不同PD-L1临界值下的客观缓解率（ORR）、疾病控制率（DCR）、风险比（HR）以及无进展生存期（PFS）和总生存期（OS）的95%置信区间（CI）。

结果

最终纳入12项研究，共6488例患者进行汇总分析。总体、PD-L1阴性、联合阳性评分（CPS）≥1、CPS≥5和CPS≥10人群的ORR分别为10%、3%、13%、20%和23%。免疫检查点抑制剂（ICI）单药治疗在总体人群和PD-L1阴性患者中未显示出生存优势。在PD-L1 CPS≥1的患者中，单药ICI治疗可延长OS（HR = 0.84，95% CI：0.74 - 0.96），但不能延长PFS（HR = 1.38，95% CI：0.91 - 2.09）。对于联合免疫治疗，总体、PD-L1阴性、CPS≥1、CPS≥5和CPS≥10人群的ORR分别为64%、57%、48%、60%和58%。根据Checkmate-649的结果，总体人群可从联合免疫治疗中获得生存益处。接受联合免疫治疗的PD-L1 CPS≥1患者的OS（HR = 0.81，95% CI：0.71 - 0.92）和PFS（HR = 0.77，95% CI：0.69 - 0.86）显著延长。