贝伐单抗联合洛莫司汀治疗复发性胶质母细胞瘤疗效与安全性的Meta分析

Meta-analysis of efficacy and safety of bevacizumab combined with lomustine in treatment of recurrent glioblastoma

目的系统评价贝伐单抗联合洛莫司汀治疗复发性胶质瘤的临床疗效与安全性。方法全面检索中英文数据库,检索随机对照试验中探讨复发性胶质瘤患者使用贝伐单抗与洛莫司汀联合治疗的临床研究,检索时间均从建库至2023-04。2名研究者分别独立检索数据库,筛查文献后对数据进行提取、分析,并分析纳入文献的偏倚风险,采用RevMan 5.4软件进行Meta分析。结果纳入6项随机对照试验,共有患者1053例(试验组523例,对照组530例)。Meta分析结果显示,贝伐单抗联合洛莫司汀治疗可显著改善复发性胶质母细胞瘤患者的无进展生存期(PFS)(HR=0.52,95%CI:0.44~0.61,P<0.05)与客观缓解率(ORR)(OR=0.33,95%CI:0.14~0.78,P<0.05),对总生存期(OS)无明显改善作用(HR=0.89,95%CI:0.75~1.07,P<0.05)。不良反应方面,贝伐单抗联合洛莫司汀治疗组的蛋白尿及三级以上不良反应发生率显著高于对照组,差异有统计学意义(P<0.05),其他不良反应与对照组比较,差异无统计学意义。结论贝伐单抗联合洛莫司汀治疗复发性胶质瘤可显著改善PFS、ORR,可优先推荐用于治疗复发性胶质母细胞瘤。同时,贝伐单抗与洛莫司汀联合治疗也与蛋白尿及三级以上不良反应率增加相关,因此在将贝伐单抗加入洛莫司汀方案之前,安全性仍需考虑。

Objective To systematically evaluate the clinical efficacy and safety of bevacizumab combined with lomustine in the treatment of recurrent glioma.Methods A comprehensive computer search was conducted in both Chinese and English databases to search randomized controlled trials on the use of bevacizumab in combination with lomustine in patients with recurrent glioma.The search time was from the establishment of the database to April 2023.Two researchers independently searched the database,screened the literature,extracted and analyzed the data,analyzed the risk of bias in the included literature,and performed a meta-analysis using software(RevMan 5.4).Results Six randomized controlled trials were included,with a total of 1053 patients(523 in experimental group and 530 in control group).The results of Meta analysis showed that bevacizumab combined with lomustine significantly improved progression-free survival(PFS)(HR=0.52,95%CI:0.44-0.61,P<0.05)and objective response rate(ORR)(OR=0.33,95%CI:0.14-0.78,P<0.05)in patients with recurrent glioblastoma,and had no significant on overall survival(OS)(HR=0.89,95%CI:0.75-1.07,P<0.05).In terms of adverse reactions:the incidence of proteinuria and grade Ⅲ or above adverse reactions in bevasizumab combined with lomustine was significantly higher than that in the control group,with statistical significance(P<0.05),while there was no statistical significance in other adverse reactions compared with the control group.Conclusions Bevacizumab combined with Lomustine can significantly improve PFS and ORR in patients with recurrent GBM,indicating that the combination therapy is recommended for the treatment of recurrent glioblastoma.At the same time,the combination of bevacizumab and lomustine is also associated with an increased rate of proteinuria and grade Ⅲ or higher adverse reactions,so safety needs to be considered before adding bevacizumab to the lomustine regimen.