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靶向PD-1/PD-L1抗体治疗晚期非小细胞肺癌的疗效和安全性的荟萃分析。

A meta-analysis of efficacy and safety of antibodies targeting PD-1/PD-L1 in treatment of advanced nonsmall cell lung cancer.

作者信息

Wang Cuihua, Yu Xuetao, Wang Wei

机构信息

Oncology Department, Shanghai Putuo District Liqun Hospital Oncology Department, Shanghai Tianyou Hospital Affiliated to Tongji University, Shanghai Radiology Department, The Third People's Hospital of Dalian, Dalian, PR China.

出版信息

Medicine (Baltimore). 2016 Dec;95(52):e5539. doi: 10.1097/MD.0000000000005539.

Abstract

BACKGROUND

Nonsmall cell lung cancer (NSCLC)-patients treated with standard chemotherapy experienced progression rapidly. A novel therapy based on programed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors showed an increasing potential in several malignancies including advanced NSCLC.

OBJECTIVES

This article is a meta-analysis aiming to systematically evaluate the efficacy and safety profiles of PD-1/PD-L1 agents in patients with NSCLC.

DATA SOURCES

Data were collected from eligible studies searched from PubMed, ScienceDirect, and Web of Science.

SYNTHESIS METHODS

Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was estimated to assess the efficacy of PD-1/PD-L1 inhibitors versus docetaxel, pooled odds ratio (OR) was calculated for objective response rate (ORR). The overall frequency was estimated for 1-year OS, 1-year progression-free survival, and ORR. A subgroup analysis among NSCLC patients tested with different epidermal growth factor receptor (EGFR) status was also performed to figure out the relationship between EGFR status and efficacy of PD-1/PD-L1 therapies. OR for occurrence of any grade and grade 3 to 5 treatment-related adverse effect was calculated for evaluating the safety of PD-1/PD-L1 therapies.

RESULTS

Nine studies were included in this analysis. The pooled HRs for OS and PFS were 0.68 (95% confidence interval [CI] 0.61-0.75) and 0.83 (95% CI 0.75-0.91), respectively, the pooled OR for ORR was 1.83 (95% CI 1.41-2.36), indicating a significant improvement in OS, PFS, and ORR. In the results of subgroup analysis, the HR for OS in NSCLC patients was 1.05 (95% CI 0.69-1.59) in patients with mutant EGFR and 0.66 (95% CI 0.57-0.77) in patients with wild-type EGFR status. OR for occurrence was 0.36 (95% CI 0.28-0.46) in any grade treatment-related adverse effect and 0.18 (95% CI 0.14-0.22) in grade 3 to 5 treatment-related adverse effect, suggesting a superior safety profile of PD-1/PD-L1 inhibitors.

CONCLUSION

The PD-1/PD-L1 therapy significantly prolonged the OS and improved the ORR, simultaneously lowering the treatment-related adverse effect events versus docetaxel.

摘要

背景

接受标准化疗的非小细胞肺癌(NSCLC)患者病情进展迅速。一种基于程序性死亡1(PD-1)/程序性死亡配体1(PD-L1)抑制剂的新型疗法在包括晚期NSCLC在内的多种恶性肿瘤中显示出越来越大的潜力。

目的

本文是一项荟萃分析,旨在系统评估PD-1/PD-L1药物在NSCLC患者中的疗效和安全性。

数据来源

数据收集自从PubMed、ScienceDirect和Web of Science检索到的符合条件的研究。

合成方法

估计总生存期(OS)和无进展生存期(PFS)的合并风险比(HR),以评估PD-1/PD-L1抑制剂与多西他赛相比的疗效,计算客观缓解率(ORR)的合并比值比(OR)。估计1年OS、1年无进展生存期和ORR的总体频率。还对不同表皮生长因子受体(EGFR)状态检测的NSCLC患者进行亚组分析,以确定EGFR状态与PD-1/PD-L1治疗疗效之间的关系。计算任何级别和3至5级治疗相关不良反应发生的OR,以评估PD-1/PD-L1治疗的安全性。

结果

本分析纳入9项研究。OS和PFS的合并HR分别为0.68(95%置信区间[CI]0.61-0.75)和0.83(95%CI 0.75-0.91),ORR的合并OR为1.83(95%CI 1.41-2.36),表明OS、PFS和ORR有显著改善。在亚组分析结果中,EGFR突变患者的NSCLC患者OS的HR为1.05(95%CI 0.69-1.59),EGFR野生型状态患者为0.66(95%CI 0.57-0.77)。任何级别治疗相关不良反应发生的OR为0.36(95%CI 0.28-0.46),3至5级治疗相关不良反应发生的OR为0.18(95%CI 0.14-0.22),表明PD-1/PD-L1抑制剂具有更好的安全性。

结论

与多西他赛相比,PD-1/PD-L治疗显著延长了OS,提高了ORR,同时降低了治疗相关不良反应事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b1/5207545/9c8414fbe1f0/medi-95-e5539-g001.jpg

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