Xu Yanan, Guan Haijing, Yu Kefu, Ji Nan, Zhao Zhigang
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
School of Pharmacy, Capital Medical University, Beijing, China.
Front Pharmacol. 2023 Jun 1;14:1191480. doi: 10.3389/fphar.2023.1191480. eCollection 2023.
To compare the efficacy and safety of treatments for patients with recurrent high-grade gliomas. Electronic databases including Pubmed, Embase, Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials (RCT) related to high-grade gliomas. The inclusion of qualified literature and extraction of data were conducted by two independent reviewers. The primary clinical outcome measures of network meta-analysis were overall survival (OS) while progression-free survival (PFS), objective response rate (ORR) and adverse event of grade 3 or higher were secondary measures. 22 eligible trials were included in the systematic review, involving 3423 patients and 30 treatment regimens. Network meta-analysis included 11 treatments of 10 trials for OS and PFS, 10 treatments of 8 trials for ORR, and 8 treatments of 7 trials for adverse event grade 3 or higher. Regorafenib showed significant benefits in terms of OS in paired comparison with several treatments such as bevacizumab (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.21-0.73), bevacizumab plus carboplatin (HR, 0.33; 95%CI, 0.16-0.68), bevacizumab plus dasatinib (HR, 0.44; 95%CI, 0.21-0.93), bevacizumab plus irinotecan (HR, 0.4; 95%CI, 0.21-0.74), bevacizumab plus lomustine (90 mg/m) (HR, 0.53; 95%CI, 0.33-0.84), bevacizumab plus lomustine (110 mg/m) (HR, 0.21; 95%CI, 0.06-0.7), bevacizumab plus vorinostat (HR, 0.42; 95%CI, 0.18-0.99), lomustine (HR, 0.5; 95%CI, 0.33-0.76), and nivolumab (HR, 0.38; 95%CI, 0.19-0.73). For PFS, only the hazard ratio between bevacizumab plus vorinostat and bevacizumab plus lomustine (90 mg/m) was significant (HR,0.51; 95%CI, 0.27-0.95). Lomustine and nivolumab conferred worse ORR. Safety analysis showed fotemustine as the best and bevacizumab plus temozolomide as the worst. The results suggested that regorafenib and bevacizumab plus lomustine (90 mg/m) provide improvements in terms of survival but may have poor ORR in patients with recurrent high-grade glioma.
比较复发性高级别胶质瘤患者不同治疗方法的疗效和安全性。检索电子数据库，包括PubMed、Embase、Cochrane图书馆和ClinicalTrials.gov，以查找与高级别胶质瘤相关的随机对照试验（RCT）。由两名独立 reviewers 进行合格文献的纳入和数据提取。网状Meta分析的主要临床结局指标为总生存期（OS），无进展生存期（PFS）、客观缓解率（ORR）以及3级或更高等级的不良事件为次要指标。系统评价纳入了22项符合条件的试验，涉及3423例患者和30种治疗方案。网状Meta分析包括10项试验中的11种治疗方法用于OS和PFS分析，8项试验中的10种治疗方法用于ORR分析，7项试验中的8种治疗方法用于3级或更高等级不良事件分析。在与几种治疗方法的配对比较中，瑞戈非尼在OS方面显示出显著优势，如贝伐单抗（风险比（HR），0.39；95%置信区间（CI），0.21 - 0.73）、贝伐单抗加卡铂（HR，0.33；95%CI，0.16 - 0.68）、贝伐单抗加达沙替尼（HR，0.44；95%CI，0.21 - 0.93）、贝伐单抗加伊立替康（HR，0.4；95%CI，0.21 - 0.74）、贝伐单抗加洛莫司汀（90mg/m²）（HR，0.53；95%CI，0.33 - 0.84）、贝伐单抗加洛莫司汀（110mg/m²）（HR，0.21；95%CI，0.06 - 0.7）、贝伐单抗加伏立诺他（HR，0.42；95%CI，0.18 - 0.99）、洛莫司汀（HR，0.5；95%CI，0.33 - 0.76）和纳武单抗（HR，0.38；95%CI，0.19 - 0.73）。对于PFS，仅贝伐单抗加伏立诺他与贝伐单抗加洛莫司汀（90mg/m²）之间的风险比具有显著性（HR，0.51；95%CI，0.27 - 0.95）。洛莫司汀和纳武单抗的ORR较差。安全性分析显示福莫司汀最佳，贝伐单抗加替莫唑胺最差。结果表明，瑞戈非尼和贝伐单抗加洛莫司汀（90mg/m²）在复发性高级别胶质瘤患者的生存方面有改善，但ORR可能较差。
