Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts.
Dana-Farber Program in Regulatory Science, Harvard Medical School, Boston, Massachusetts.
Neuro Oncol. 2018 Jul 5;20(8):1034-1043. doi: 10.1093/neuonc/noy027.
There have been few treatment advances for patients with glioblastoma (GBM) despite increasing scientific understanding of the disease. While factors such as intrinsic tumor biology and drug delivery are challenges to developing efficacious therapies, it is unclear whether the current clinical trial landscape is optimally evaluating new therapies and biomarkers.
We queried ClinicalTrials.gov for interventional clinical trials for patients with GBM initiated between January 2005 and December 2016 and abstracted data regarding phase, status, start and end dates, testing locations, endpoints, experimental interventions, sample size, clinical presentation/indication, and design to better understand the clinical trials landscape.
Only approximately 8%-11% of patients with newly diagnosed GBM enroll on clinical trials with a similar estimate for all patients with GBM. Trial duration was similar across phases with median time to completion between 3 and 4 years. While 93% of clinical trials were in phases I-II, 26% of the overall clinical trial patient population was enrolled on phase III studies. Of the 8 completed phase III trials, only 1 reported positive results. Although 58% of the phase III trials were supported by phase II data with a similar endpoint, only 25% of these phase II trials were randomized.
The clinical trials landscape for GBM is characterized by long development times, inadequate dissemination of information, suboptimal go/no-go decision making, and low patient participation.
尽管人们对胶质母细胞瘤（GBM）的发病机制有了更深入的了解，但患者的治疗手段仍鲜有进展。内在肿瘤生物学和药物递送等因素是开发有效疗法的挑战，但目前的临床试验格局是否能最佳地评估新疗法和生物标志物尚不清楚。
我们在 ClinicalTrials.gov 上查询了 2005 年 1 月至 2016 年 12 月期间为 GBM 患者启动的干预性临床试验，并摘录了关于试验阶段、状态、开始和结束日期、检测地点、终点、实验干预、样本量、临床表现/指征和设计的数据，以更好地了解临床试验格局。
新诊断为 GBM 的患者中仅有约 8%-11%参加临床试验，所有 GBM 患者的这一比例也类似。各阶段的试验持续时间相似，完成中位数时间在 3 至 4 年之间。尽管 93%的临床试验处于 I-II 期，但 26%的总体临床试验患者人群参加了 III 期研究。在已完成的 8 项 III 期试验中，只有 1 项报告了阳性结果。尽管 58%的 III 期试验得到了具有相似终点的 II 期数据的支持，但这些 II 期试验中仅有 25%是随机的。
GBM 的临床试验格局的特点是开发时间长、信息传播不足、决策不理想以及患者参与度低。
