Ippen Franziska Maria, Scherm Angelika, Kessler Tobias, Hau Peter, Agkatsev Sarina, Baurecht Hansjörg, Wick Wolfgang, Knüttel Helge, Leitzmann Michael F, Seliger-Behme Corinna
Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
Wilhelm Sander-NeuroOncology Unit and Department of Neurology, University Hospital Regensburg, Regensburg, Germany.
Cancer Med. 2024 Jun;13(12):e7362. doi: 10.1002/cam4.7362.
Glioblastoma (GB) is the most common malignant primary brain tumor in adults and is associated with a poor prognosis. Current treatment guidelines outline the standard of care for patients with newly diagnosed GB; however, there is currently no well-established consensus for the treatment of progressive GB. With this systematic meta-analysis of recently published randomized controlled trials (RCTs), we aim to establish evidence on targeted agents in the treatment of patients with progressive GB.
We conducted searches across the Cochrane Library, Pubmed, MEDLINE (Ovid), ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform and Google Scholar, encompassing the time span from 1954 to 2022, aiming to identify RCTs evaluating targeted therapies in patients with progressive GB. In order to perform a random-effects meta-analysis, we extracted hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS).
We included 16 RCTs (n = 3025 patients) in the systematic meta-analysis. Formally, regorafenib (RR 0.50; 95% CI 0.33-0.75), Depatux-M + TMZ (RR 0.66; 95% CI 0.47-0.93) and rindopepimut + bevacizumab (RR 0.53; 95% CI 0.32-0.88) were associated with an improved OS compared to the control arm. The combination of bevacizumab + CCNU (RR = 0.49; 95% CI 0.35-0.69) and regorafenib (RR 0.65; 95% CI 0.44-0.95) were formally associated with improved PFS.
The aim of this systematic meta-analysis was to establish evidence for the use of targeted therapies in progressive GB. While some studies demonstrated benefits for OS and/or PFS, those results have to be interpreted with caution as most studies had major methodological weaknesses, including potential differences in sample size, trial design, or the initial distribution of prognostic factors.
胶质母细胞瘤（GB）是成人中最常见的原发性恶性脑肿瘤，预后较差。当前的治疗指南概述了新诊断GB患者的护理标准；然而，目前对于进展性GB的治疗尚无公认的共识。通过对最近发表的随机对照试验（RCT）进行这项系统的荟萃分析，我们旨在确立靶向药物治疗进展性GB患者的证据。
我们在Cochrane图书馆、PubMed、MEDLINE（Ovid）、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台和谷歌学术上进行了检索，时间跨度为1954年至2022年，旨在识别评估进展性GB患者靶向治疗的RCT。为了进行随机效应荟萃分析，我们提取了总生存期（OS）和无进展生存期（PFS）的风险比（HR）。
我们在系统荟萃分析中纳入了16项RCT（n = 3025例患者）。正式来说，与对照组相比，瑞戈非尼（RR 0.50；95%CI 0.33 - 0.75）、Depatux - M +替莫唑胺（TMZ）（RR 0.66；95%CI 0.47 - 0.93）和rindopepimut +贝伐单抗（RR 0.53；95%CI 0.32 - 0.88）与OS改善相关。贝伐单抗 +洛莫司汀（CCNU）（RR = 0.49；95%CI 0.35 - 0.69）和瑞戈非尼（RR 0.65；95%CI 0.44 - 0.95）与PFS改善正式相关。
这项系统荟萃分析的目的是确立在进展性GB中使用靶向治疗的证据。虽然一些研究显示对OS和/或PFS有益，但这些结果必须谨慎解读，因为大多数研究存在重大方法学缺陷，包括样本量、试验设计或预后因素初始分布的潜在差异。
