晚期胰腺癌靶向治疗的系统评价与荟萃分析

Systematic review and meta-analysis on targeted therapy in advanced pancreatic cancer.

作者信息

Ciliberto Domenico, Staropoli Nicoletta, Chiellino Silvia, Botta Cirino, Tassone Pierfrancesco, Tagliaferri Pierosandro

机构信息

Medical Oncology and Translational Medical Oncology Units, Department of Experimental and Clinical Medicine, Magna Graecia University, AOU Materdomini Catanzaro, CampusSalvatore Venuta, Catanzaro 88100, Italy.

出版信息

Pancreatology. 2016 Mar-Apr;16(2):249-58. doi: 10.1016/j.pan.2016.01.003. Epub 2016 Jan 20.

DOI:10.1016/j.pan.2016.01.003

PMID:26852170

Abstract

AIM

A systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer.

METHODS

By searching different literature databases and major cancer meetings proceedings, data from all randomized clinical trials designed to investigate molecular targeted agents in the treatment of advanced pancreatic cancer were collected. The time-frame between January 2007 and March 2015 was selected. Data on predefined end-points, including overall survival, progression-free survival in terms of Hazard Ratio and response-rate were extracted and analyzed by a random effects model. Pooled data analysis was performed according to the DerSimonian and Laird test. The occurrence of publication bias was investigated through Begg's test by visual inspection of funnel plots.

RESULTS

Twenty-seven randomized clinical trials for a total of 8205 patients were selected and included in the final analysis. A significant benefit was demonstrated for anti-EGFR agents on overall survival (HR = 0.880; 95% confidence interval (CI) 0.797-0.972; p = 0.011). In the pooled analysis no benefit on overall survival (OS: pooled HR = 0.957; 95%CI 0.900-1.017; p = 0.153), or progression-free survival (PFS: pooled HR = 0.908; 95%CI 0.817-1.010; p = 0.075) for targeted-based therapies as compared to conventional treatments could be demonstrated. No advantage was reported in response-rate (OR for RR = 1.210; 95%CI 0.990-1.478; p = 0.063). Begg's funnel plot showed no evidence of publication bias.

CONCLUSION

The use of molecular targeted agents does not translate into clinical benefit. Therefore, our work highlights the need to identify predictive factors for patient selection and rationally designed clinical trials.

摘要

目的

通过对文献进行系统评价和荟萃分析，评估靶向治疗对晚期胰腺癌的影响。

方法

通过检索不同的文献数据库和主要癌症会议论文集，收集所有旨在研究分子靶向药物治疗晚期胰腺癌的随机临床试验数据。选择2007年1月至2015年3月的时间范围。提取包括总生存期、基于风险比的无进展生存期和缓解率等预定义终点的数据，并采用随机效应模型进行分析。根据DerSimonian和Laird检验进行合并数据分析。通过Begg检验并直观检查漏斗图来研究发表偏倚的发生情况。

结果

共选择27项随机临床试验，涉及8205例患者并纳入最终分析。结果表明抗表皮生长因子受体（EGFR）药物对总生存期有显著益处（风险比[HR]=0.880；95%置信区间[CI]0.797-0.972；p=0.011）。在合并分析中，与传统治疗相比，基于靶向治疗在总生存期（OS：合并HR=0.957；95%CI 0.900-1.017；p=0.153）或无进展生存期（PFS：合并HR=0.908；95%CI 0.817-1.010；p=0.075）方面未显示出益处。缓解率方面未报告有优势（缓解率的比值比[OR]=1.210；95%CI 0.990-1.478；p=0.063）。Begg漏斗图未显示发表偏倚的证据。