Department of Neurosurgery, The First People's Hospital of Shuangliu District, No.120 Chengbei Uppersteet, Chengdu, Shuangliu District, 610200, China.
Department of Neurosurgery, West China Hospital, Sichuan University, No.37 Guoxue Lane, Chengdu, Wuhou District, 610041, China.
Neurosurg Rev. 2024 Aug 22;47(1):458. doi: 10.1007/s10143-024-02664-x.
This study aimed to evaluate the effects of dabrafenib and/or trametinib therapy in BRAF v600-mutant glioma treatment. PubMed, the Cochrane Library, EMBASE and Web of Science were searched from inception to Sep 2023. Inclusion criteria were designed based on the PICO principle to select relevant articles. Search keywords included 'dabrafenib', 'trametinib', 'glioma' and other related keywords. Outcomes included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and death events. Methodological index for non-randomized studies (MINORS) was used to assess the methodological quality. Stata 14.0 was selected to perform the Cochrane Q and I statistics to test the heterogeneity among all studies. As for publication bias assessment and sensitivity analysis, the funnel plot, Egger regression test, Begg test, and trim and fill method were selected. Including 8 studies for meta-analysis. The pooled results of the single-arm trials showed that the median PFS and median OS after treatment were 6.10 months and 22.73 months, respectively. Notably, this study found a high incidence of AEs and death events of 50% and 43% after treatment. All the above findings were statistically significant. Also, this study statistically supported the advantage of disease response improvement after the combination therapy in BRAF v600-mutant glioma patients, which were shown as a pooled rate of PR (30%), a pooled rate of CR (18%), and a pooled rate of ORR (39%). And the AE rate was lower in the monotherapy group (AE: 25%) than in the combination treatment group (AE: 60%). Sensitivity analysis indicated that all the results were robust. Based on current literature outcomes, dabrafenib and/or trametinib may lead to the median PFS of 6.10 months and median OS as 22.73 months for BRAF v600-mutant glioma patients, and the safety of monotherapy is better than that of combination therapy. This conclusion needs to be treated with caution and further verified.
本研究旨在评估达拉非尼和/或曲美替尼治疗 BRAF v600 突变型脑胶质瘤的疗效。从建库至 2023 年 9 月，检索了 PubMed、Cochrane 图书馆、EMBASE 和 Web of Science。根据 PICO 原则设计纳入标准，以选择相关文章。搜索关键词包括“达拉非尼”、“曲美替尼”、“脑胶质瘤”和其他相关关键词。结局包括总生存期（OS）、无进展生存期（PFS）、不良事件（AEs）和死亡事件。非随机研究方法学指数（MINORS）用于评估方法学质量。选择 Stata 14.0 进行 Cochrane Q 和 I 统计检验，以检验所有研究之间的异质性。对于发表偏倚评估和敏感性分析，选择漏斗图、Egger 回归检验、Begg 检验和修剪填充方法。纳入 8 项研究进行荟萃分析。单臂试验的汇总结果显示，治疗后中位 PFS 和中位 OS 分别为 6.10 个月和 22.73 个月。值得注意的是，这项研究发现治疗后 AEs 和死亡事件的发生率分别高达 50%和 43%。所有这些发现均具有统计学意义。此外，这项研究还从统计学上支持了 BRAF v600 突变型脑胶质瘤患者联合治疗后疾病反应改善的优势，表现为 PR （30%）、CR （18%）和 ORR （39%）的汇总率。而且，单药治疗组的 AE 发生率较低（AE：25%），低于联合治疗组（AE：60%）。敏感性分析表明，所有结果均稳健。基于目前的文献结果，达拉非尼和/或曲美替尼可能导致 BRAF v600 突变型脑胶质瘤患者的中位 PFS 为 6.10 个月，中位 OS 为 22.73 个月，且单药治疗的安全性优于联合治疗。这一结论需要谨慎对待，并进一步验证。
