PD-1 或 PD-L1 抑制剂及 PD-L1 表达状态在癌症中的疗效：荟萃分析。

Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis.

机构信息

Center for Precision Medicine, 109 Xueyuan West Road, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.

出版信息

BMJ. 2018 Sep 10;362:k3529. doi: 10.1136/bmj.k3529.

DOI:10.1136/bmj.k3529

PMID:30201790

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6129950/

Abstract

OBJECTIVE

To evaluate the relative efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive and PD-L1 negative.

DESIGN

Meta-analysis of randomised controlled trials.

DATA SOURCES

PubMed, Embase, Cochrane database, and conference abstracts presented at the American Society of Clinical Oncology and European Society of Medical Oncology up to March 2018.

REVIEW METHODS

Studies of PD-1 or PD-L1 inhibitors (avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab) that had available hazard ratios for death based on PD-L1 positivity or negativity were included. The threshold for PD-L1 positivity or negativity was that PD-L1 stained cell accounted for 1% of tumour cells, or tumour and immune cells, assayed by immunohistochemistry staining methods.

RESULTS

4174 patients with advanced or metastatic cancers from eight randomised controlled trials were included in this study. Compared with conventional agents, PD-1 or PD-L1 inhibitors were associated with significantly prolonged overall survival in both patients that were PD-L1 positive (n=2254, hazard ratio 0.66, 95% confidence interval 0.59 to 0.74) and PD-L1 negative (1920, 0.80, 0.71 to 0.90). However, the efficacies of PD-1 or PD-L1 blockade treatment in patients that were PD-L1 positive and PD-L1 negative were significantly different (P=0.02 for interaction). Additionally, in both patients that were PD-L1 positive and PD-L1 negative, the long term clinical benefits from PD-1 or PD-L1 blockade were observed consistently across interventional agent, cancer histotype, method of randomisation stratification, type of immunohistochemical scoring system, drug target, type of control group, and median follow-up time.

CONCLUSIONS

PD-1 or PD-L1 blockade therapy is a preferable treatment option over conventional therapy for both patients that are PD-L1 positive and PD-L1 negative. This finding suggests that PD-L1 expression status alone is insufficient in determining which patients should be offered PD-1 or PD-L1 blockade therapy.

摘要

目的

评估程序性细胞死亡蛋白 1（PD-1）或程序性细胞死亡配体 1（PD-L1）抑制剂与常规药物在 PD-L1 阳性和 PD-L1 阴性癌症患者中的相对疗效。

设计

随机对照试验的荟萃分析。

数据来源

PubMed、Embase、Cochrane 数据库以及截至 2018 年 3 月在美国临床肿瘤学会和欧洲肿瘤内科学会上提交的会议摘要。

检索方法

纳入了 PD-1 或 PD-L1 抑制剂（avelumab、atezolizumab、durvalumab、nivolumab 和 pembrolizumab）的研究，这些研究具有基于 PD-L1 阳性或阴性的死亡风险比。PD-L1 阳性或阴性的阈值是肿瘤细胞或肿瘤和免疫细胞中 PD-L1 染色细胞占 1%，通过免疫组织化学染色方法检测。

结果

8 项随机对照试验中共有 4174 名晚期或转移性癌症患者纳入本研究。与常规药物相比，PD-1 或 PD-L1 抑制剂在 PD-L1 阳性（n=2254，风险比 0.66，95%置信区间 0.59 至 0.74）和 PD-L1 阴性（1920，0.80，0.71 至 0.90）患者中均显著延长了总生存期。然而，PD-1 或 PD-L1 阻断治疗在 PD-L1 阳性和 PD-L1 阴性患者中的疗效差异具有显著意义（P=0.02 用于交互作用）。此外，在 PD-L1 阳性和 PD-L1 阴性患者中，PD-1 或 PD-L1 阻断的长期临床获益在干预药物、癌症组织类型、随机分组分层方法、免疫组织化学评分系统类型、药物靶点、对照组类型和中位随访时间方面均一致。