The clinical trials landscape for glioblastoma: is it adequate to develop new treatments?
The clinical trials landscape for glioblastoma: is it adequate to develop new treatments?
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DOI：
10.1093/neuonc/noy027
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发表时间：
2018-08-01
期刊：
影响因子：
15.9
通讯作者：
Alexander, Brian M.
中科院分区：
文献类型：
--
作者：
Vanderbeek, Alyssa M.;Rahman, Rifaquat;Alexander, Brian M.
背景资料。尽管对胶质母细胞瘤(GBM)的科学认识不断增加，但对这种疾病的治疗进展很少。虽然固有的肿瘤生物学和药物输送等因素是开发有效治疗方法的挑战，但目前尚不清楚当前的临床试验环境是否正在最佳地评估新的治疗方法和生物标志物。我们在ClinicalTrials.gov上查询了2005年1月至2016年12月期间开始的针对GBM患者的介入临床试验，并提取了关于阶段、状态、开始和结束日期、测试地点、终点、实验干预、样本量、临床表现/适应症和设计的数据，以更好地了解临床试验环境。只有大约8%-11%的新诊断的GBM患者参加了临床试验，对所有GBM患者的估计类似。不同阶段的试验持续时间相似，完成试验的中位时间在3到4年之间。虽然93%的临床试验处于I-II阶段，但总临床试验患者群体中有26%参与了III阶段研究。在完成的8个第三阶段试验中，只有1个报告了阳性结果。虽然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期试验中只有25%是随机的。GBM的临床试验环境的特点是开发时间长，信息传播不充分，进行/不进行决策的次优，以及患者参与度低。
Background. 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.Methods. 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.Results. 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.Conclusions. 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.