UMass Chan Medical School, Worcester, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
Pediatr Blood Cancer. 2023 May;70(5):e30106. doi: 10.1002/pbc.30106. Epub 2022 Dec 2.
Understanding the landscape of clinical trials for patients with neuroblastoma may inform efforts to improve drug development.
We evaluated therapeutic trials for patients with neuroblastoma from 2011 to 2020 in our search using clinical trial information from ClinicalTrials.gov, Clinicaltrialregister.eu, PubMed, and American Society of Clinical Oncology (ASCO) annual meeting collection. Trends in trials and treatments over time were evaluated qualitatively.
A total of 192 trials met inclusion criteria. A median of 20.5 trials were started per year, which was stable over time. There were 87 (45%) phase 1, 100 (51%) phase 2, and only five (2.6%) phase 3 trials. The median time to completion was 4.9 years for phase 1 and 2 trials (no phase 3 trials reported as completed during the study period). In all, 34% of trials were international, while 20% of trials were intercontinental. Eighty-nine percent of nonmyeloablative trials included at least one novel agent. 48% of these trials studied combination therapies, and 86% of these combinations included conventional chemotherapy. Among 157 trials that included a targeted agent, 78 targets were identified, with GD2 being the primary target under investigation in 16.7% of these trials. Only eight trials were included in regulatory decisions, which led to European Medicines Agency (EMA) or Food and Drug Administration (FDA) approval for neuroblastoma.
The large number of trials initiated per year, the range of targets, and the rate of intercontinental collaboration are encouraging. The paucity of late-stage trials, the prolonged trial duration, and relative lack of combination studies are major causes of concern. This work will inform future drug development for neuroblastoma.
了解神经母细胞瘤患者临床试验的现状，可能有助于促进药物开发。
我们使用临床试验信息从 ClinicalTrials.gov、Clinicaltrialregister.eu、PubMed 和美国临床肿瘤学会（ASCO）年会集进行搜索，评估了 2011 年至 2020 年期间神经母细胞瘤患者的治疗试验。定性评估了随时间推移的试验和治疗趋势。
共有 192 项试验符合纳入标准。每年平均启动 20.5 项试验，且较为稳定。其中 87 项（45%）为 1 期，100 项（51%）为 2 期，仅 5 项（2.6%）为 3 期。1 期和 2 期试验的中位完成时间为 4.9 年（研究期间未报告完成的 3 期试验）。共有 34%的试验为国际试验，20%的试验为洲际试验。89%的非清髓性试验至少包含一种新型药物。这些试验中 48%研究了联合疗法，这些联合疗法中有 86%包含常规化疗。在包括靶向药物的 157 项试验中，确定了 78 个靶点，其中 16.7%的试验将 GD2 作为主要研究靶点。只有 8 项试验被纳入监管决策，这导致欧洲药品管理局（EMA）或美国食品和药物管理局（FDA）批准了神经母细胞瘤的药物。
每年启动的试验数量多、靶点范围广、洲际合作率高，这令人鼓舞。但晚期试验数量少、试验持续时间长、联合研究相对缺乏，是主要关注的问题。这项工作将为神经母细胞瘤的未来药物开发提供信息。
