Purpose: A glioblastoma (GBM) is a primary brain tumor with significant unmet therapeutic needs. Immune checkpoint inhibitors (ICIs) have marked therapeutic benefits in many different cancers but have yet to show benefit for most GBM patients in phase III trials. Methods: A systematic review querying ClinicalTrials.gov for prospective clinical trials investigating ICI in GBM between 1950 and July 2024 was performed. Search terms comprised 11 distinct ICIs. Data abstracted include clinical trial NCT numbers with study titles and status, enrollment information, interventions, and more. Clinical trial identifying information, interventions, and outcomes were extracted. Results: One hundred and seventeen clinical trials were identified; four were phase 3. Most involved PD-1 or CTLA-4 blockade as monotherapy or in combination with standard-of-care. The large, randomized trials included CHECKMATE 143, CHECKMATE 498, CHECKMATE 548, and NRG BN007. These showed no improvement in median overall survival or progression-free survival in unselected patients. Biomarker-directed analyses suggest that a subset of GBM patients may benefit. Conclusions: ICI for the treatment of GBM has not demonstrated clear evidence of efficacy thus far. This review serves as a quick reference of ICI trial results in GBM. Biomarker-driven patient selection and/or novel approaches to overcome resistance mechanisms remain areas of viable inquiry.
目的：胶质母细胞瘤（GBM）是一种原发性脑肿瘤，其治疗需求远未得到满足。免疫检查点抑制剂（ICIs）在多种癌症中显示出显著疗效，但在III期临床试验中尚未对大多数GBM患者表现出明确获益。方法：本研究对ClinicalTrials.gov数据库中1950年至2024年7月期间开展的GBM免疫检查点抑制剂前瞻性临床试验进行了系统性检索。检索范围涵盖11种不同的免疫检查点抑制剂。提取的数据包括临床试验的NCT编号、研究标题与状态、入组信息、干预措施等。同时对试验识别信息、干预方案及研究结果进行了归纳。结果：共识别出117项临床试验，其中4项为III期研究。多数试验涉及PD-1或CTLA-4抑制剂单药或联合标准治疗方案。大型随机试验包括CHECKMATE 143、CHECKMATE 498、CHECKMATE 548及NRG BN007。这些研究显示，在未经选择的患者中，中位总生存期或无进展生存期均未得到改善。生物标志物导向的分析提示特定GBM亚群患者可能获益。结论：目前免疫检查点抑制剂治疗GBM尚未展现明确疗效证据。本综述可为GBM免疫检查点抑制剂临床试验结果提供快速参考。基于生物标志物的患者筛选和/或克服耐药机制的新策略仍是值得深入探索的研究方向。
Immune Checkpoint Inhibitors in Glioblastoma IDHwt Treatment: A Systematic Review
肿瘤(癌症)患者之家