Watanabe Shinya, Nonaka Takahiro, Maeda Makoto, Sugii Narushi, Hashimoto Koichi, Takano Shingo, Koyanagi Tomoyoshi, Yamada Masanobu, Arakawa Yoshihiro, Ishikawa Eiichi
Department of Neurosurgery, Mito Kyodo General Hospital, Tsukuba University Hospital Mito Area Medical Education Center, 3-2-7 Miyamachi, Mito, Ibaraki, 310-0015, Japan.
Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Ther Innov Regul Sci. 2023 May;57(3):603-610. doi: 10.1007/s43441-022-00494-x. Epub 2023 Jan 5.
Response Evaluation Criteria in Solid Tumors (RECIST)-based response rates are commonly used as efficacy endpoints in phase II clinical trials for solid tumors. However, no consensus has been reached concerning adequate efficacy endpoints for phase II clinical trials targeting meningioma. Irregularity of lesions after resection, and varying degrees of dysplasia and histologic subtypes make establishing an appropriate efficacy evaluation difficult.
We analyzed primary efficacy endpoints (PEEs) and background factors from 48 trials retrieved from ClinicalTrials.gov ( https://clinicaltrials.gov/ ) using the search criteria "meningioma," "interventional," "phase II," and "study start 4/1/2001 to 3/31/2021." Primary purpose of the study was efficacy endpoint setting in overall population and three subgroups.
Among 45 PEEs set in the 39 trials included; 33 trials with single PEE, and six trials with double PEEs, 17/45 (38%) trials adopted progression-free survival (PFS) rate, 15/45 (33%) trials response rate (seven Macdonald criteria or modified, three RECIST, three volumetric estimation, one RANO criteria, one unknown), 10/45 (22%) PFS, 1/45 (2%) OS, and 2/45 (4%) other endpoints. Although 26 PEEs were time-to-event endpoints, 19 of the 26 PEEs were single-arm studies.
Time-to-event efficacy endpoints were often compared to historical data, and two-dimensional evaluation is more suitable than one-dimensional one. Accumulation of prognostic data is essential to standardize time-to-event efficacy endpoints. Considering the difficulty of setting design for phase II clinical studies targeting meningioma, evaluation might be done with multiple efficacy endpoints.
基于实体瘤疗效评价标准（RECIST）的缓解率通常用作实体瘤II期临床试验的疗效终点。然而，针对脑膜瘤的II期临床试验，关于充分的疗效终点尚未达成共识。切除术后病变的不规则性以及不同程度的发育异常和组织学亚型使得建立合适的疗效评估变得困难。
我们使用搜索标准“脑膜瘤”、“介入性”、“II期”和“研究开始时间2001年4月1日至2021年3月31日”，分析了从ClinicalTrials.gov（https://clinicaltrials.gov/）检索到的48项试验的主要疗效终点（PEEs）和背景因素。该研究的主要目的是确定总体人群和三个亚组的疗效终点。
在纳入的39项试验中设定的45个PEEs中；33项试验有单一PEE，6项试验有双重PEE，17/45（38%）的试验采用无进展生存期（PFS）率，15/45（33%）的试验采用缓解率（7项Macdonald标准或改良标准、3项RECIST标准、3项体积评估标准、1项RANO标准、1项未知），10/45（22%）采用PFS，1/45（2%）采用总生存期（OS），2/45（4%）采用其他终点。虽然26个PEEs是事件发生时间终点，但26个PEEs中的19个是单臂研究。
事件发生时间疗效终点常与历史数据进行比较，二维评估比一维评估更合适。积累预后数据对于标准化事件发生时间疗效终点至关重要。考虑到针对脑膜瘤的II期临床研究设置设计的难度，可能需要采用多个疗效终点进行评估。
