Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Neuro Oncol. 2024 Feb 2;26(2):211-225. doi: 10.1093/neuonc/noad211.
Glioblastoma (GBM)'s median overall survival is almost 21 months. Six phase 3 immunotherapy clinical trials have recently been published, yet 5/6 did not meet approval by regulatory bodies. For the sixth, approval is uncertain. Trial failures result from multiple factors, ranging from intrinsic tumor biology to clinical trial design. Understanding the clinical and basic science of these 6 trials is compelled by other immunotherapies reaching the point of advanced phase 3 clinical trial testing. We need to understand more of the science in human GBMs in early trials: the "window of opportunity" design may not be best to understand complex changes brought about by immunotherapeutic perturbations of the GBM microenvironment. The convergence of increased safety of image-guided biopsies with "multi-omics" of small cell numbers now permits longitudinal sampling of tumor and biofluids to dissect the complex temporal changes in the GBM microenvironment as a function of the immunotherapy.
胶质母细胞瘤（GBM）的中位总生存期接近 21 个月。最近发表了六项三期免疫疗法临床试验，但有五项/六项未能获得监管机构的批准。第六项的批准情况仍不确定。试验失败的原因有多种，包括内在肿瘤生物学和临床试验设计。随着其他免疫疗法进入高级三期临床试验测试，有必要了解这 6 项试验的临床和基础科学。我们需要在早期试验中了解更多人类 GBM 的科学知识：“窗口期”设计可能不是了解免疫治疗对 GBM 微环境产生复杂影响的最佳方法。随着图像引导活检安全性的提高，以及单细胞数量的“多组学”的发展，现在可以对肿瘤和生物液进行纵向采样，以剖析免疫治疗时 GBM 微环境的复杂时间变化。
