Department of Neurosurgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
Department of Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
Med Oncol. 2024 Sep 24;41(11):250. doi: 10.1007/s12032-024-02501-7.
For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma. This study aimed to assess the current clinical trial landscape to assess the role of molecular biomarkers in trials on recurrent glioblastoma treatment. The database ClinicalTrials.gov was used to identify not yet completed clinical trials on recurrent glioblastoma in adults. Recruiting studies were assessed to investigate the role of molecular criteria, which were retrieved as detailed as possible. Primary outcome was molecular criteria used as selection criteria for study participation. Next to this, details on moment and method of testing, and targets and drugs studied, were collected. In 76% (181/237) of the included studies, molecular criteria were not included in the study design. Of the remaining 56 studies, at least one specific genomic alteration as selection criterium for study participation was required in 33 (59%) studies. Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Of the immunotherapies, CAR-T therapies were the most frequently studied therapies. Previously, genomics studies have revealed the presence of potentially actionable alterations in glioblastoma. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments.
对于胶质母细胞瘤患者而言，目前的疗效靶向治疗仍然有限。之前研究的大多数分子疗法在该人群中缺乏疗效。需要更多的试验来研究生物标志物在（复发性）胶质母细胞瘤中的实际可操作性。本研究旨在评估当前临床试验的格局，以评估分子生物标志物在复发性胶质母细胞瘤治疗试验中的作用。使用 ClinicalTrials.gov 数据库来确定尚未完成的关于成人复发性胶质母细胞瘤的临床试验。评估了正在招募的研究，以调查分子标准的作用，尽可能详细地检索了这些标准。主要结果是作为研究参与选择标准的分子标准。此外，还收集了关于测试时间和方法以及研究目标和药物的详细信息。在纳入的 237 项研究中，有 76%（181/237）的研究未将分子标准纳入研究设计。在其余的 56 项研究中，至少有 33 项（59%）研究将特定的基因组改变作为研究参与的选择标准。最常研究的是 EGFR、CDKN2A/B 或 C、CDK4/6 和 RB 的改变，以及相应的药物 abemaciclib 和 ribociclib。在免疫疗法中，CAR-T 疗法是研究最多的疗法。以前的基因组学研究表明，胶质母细胞瘤中存在潜在的可靶向改变。我们的研究表明，目前针对复发性胶质母细胞瘤患者的靶向治疗的潜在疗效尚未转化为基于基因组的试验。强化基于基因组的试验可能有助于为靶向治疗的有效性提供证据。
