Baskaran Archit Bharathwaj, Kozel Olivia A, Venkatesh Omkar, Wainwright Derek A, Sonabend Adam M, Heimberger Amy B, Lukas Rimas Vincas
Department of Neurology, The University of Chicago, Chicago, IL 60637, USA.
Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
Cancers (Basel). 2024 Dec 12;16(24):4148. doi: 10.3390/cancers16244148.
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.
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.
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.
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.
胶质母细胞瘤（GBM）是一种主要的脑肿瘤，存在重大未满足的治疗需求。免疫检查点抑制剂（ICI）在许多不同癌症中具有显著的治疗益处，但在III期试验中尚未显示对大多数GBM患者有益。
对ClinicalTrials.gov进行系统检索，以查询1950年至2024年7月期间调查GBM中ICI的前瞻性临床试验。检索词包括11种不同的ICI。提取的数据包括临床试验NCT编号、研究标题和状态、入组信息、干预措施等。提取临床试验识别信息、干预措施和结果。
确定了117项临床试验；4项为3期试验。大多数试验涉及将PD-1或CTLA-4阻断作为单一疗法或与标准治疗联合使用。大型随机试验包括CHECKMATE 143、CHECKMATE 498、CHECKMATE 548和NRG BN007。这些试验表明，未选择的患者中位总生存期或无进展生存期没有改善。生物标志物导向分析表明，一部分GBM患者可能受益。
迄今为止，ICI治疗GBM尚未显示出明确的疗效证据。本综述可作为GBM中ICI试验结果的快速参考。生物标志物驱动的患者选择和/或克服耐药机制的新方法仍然是可行的研究领域。
