脑肿瘤 I 期临床试验的近况:探索性疗效终点的监管科学研究》。

IF 2 4区 医学 Q4 MEDICAL INFORMATICS
Shinya Watanabe, Takahiro Nonaka, Makoto Maeda, Masanobu Yamada, Narushi Sugii, Koichi Hashimoto, Shingo Takano, Tomoyoshi Koyanagi, Yoshihiro Arakawa, Eiichi Ishikawa
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引用次数: 0

摘要

背景:I 期试验中适当的探索性疗效数据对后续阶段至关重要。由于脑肿瘤(BT)的特殊性,有必要采用不同的疗效评估策略。我们对涉及脑肿瘤的 I 期试验中的探索性疗效评估进行了研究:使用 Clarivate 的 Cortellis™,对 2020 年至 2022 年进行的 42 项 BT 干预的 I 期试验的疗效终点进行了分析,这些终点被设定为主要终点(PE)或次要终点(SE)。此外,这些指标还在两个分组中进行了比较:仅包括BTs的试验(A组)和包括混合实体瘤BTs的试验(B组):所选研究包括 1.5 个 PE(范围为 1-6)和 5 个 SE(范围为 0-19)。分别有 2 项(5%)和 31 项(78%)试验将疗效终点列为 PE 和 SE。在后 31 项包含 94 个疗效终点的试验中,分别有 24、22、20、9 和 8 项试验反映了总反应率 (ORR)、无进展生存期 (PFS)、总生存期 (OS)、反应持续时间 (DOR) 和疾病控制率 (DCR)。BT的总反应率是通过各种方法确定的;然而,A组比B组更少使用实体瘤反应评估标准(RECIST)(P = 0.0039):最近的 I 期试验将疗效终点作为 SE,其中约 50% 的试验包括 ORR、PFS 或 OS,约 25% 的试验包括 DOR 或 DCR。对于 BT 的成像评估还没有既定的标准。涉及混合实体瘤队列的 I 期试验揭示了设计 BT 探索性疗效评估方法所面临的挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Recent Status of Phase I Clinical Trials for Brain Tumors: A Regulatory Science Study of Exploratory Efficacy Endpoints.

Recent Status of Phase I Clinical Trials for Brain Tumors: A Regulatory Science Study of Exploratory Efficacy Endpoints.

Background: Appropriate exploratory efficacy data from Phase I trials are vital for subsequent phases. Owing to the uniqueness of brain tumors (BTs), use of different strategies to evaluate efficacy is warranted. We studied exploratory efficacy evaluation in Phase I trials involving BTs.

Methods: Using Clarivate's Cortellis, 42 Phase I trials of BT interventions conducted from 2020 to 2022 were analyzed for efficacy endpoints, which were set as primary endpoints (PEs) or secondary endpoints (SEs). Additionally, these metrics were compared in two subgroups: trials including only BTs (Group-A) and those including BTs among mixed solid tumors (Group-B).

Results: Selected studies included a median of 1.5 PEs (range, 1-6) and 5 SEs (range, 0-19). Efficacy endpoints were included as PEs and SEs in 2 (5%) and 31 (78%) trials, respectively. Among the latter 31 trials that included 94 efficacy endpoints, 24, 22, 20, 9, and 8 reflected overall response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and disease control rate (DCR), respectively. ORR for BT was determined using various methods; however, the Response Evaluation Criteria in Solid Tumors (RECIST) was used less frequently in Group-A than in Group-B (p = 0.0039).

Conclusions: Recent Phase I trials included efficacy endpoints as SEs, with ORR, PFS, or OS included in ~ 50% trials and DOR or DCR in ~ 25%. No established criteria exist for imaging evaluation of BTs. Phase I trials involving mixed solid tumor cohorts revealed challenges in designing methods to assess the exploratory efficacy of BTs.

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来源期刊
Therapeutic innovation & regulatory science
Therapeutic innovation & regulatory science MEDICAL INFORMATICS-PHARMACOLOGY & PHARMACY
CiteScore
3.40
自引率
13.30%
发文量
127
期刊介绍: Therapeutic Innovation & Regulatory Science (TIRS) is the official scientific journal of DIA that strives to advance medical product discovery, development, regulation, and use through the publication of peer-reviewed original and review articles, commentaries, and letters to the editor across the spectrum of converting biomedical science into practical solutions to advance human health. The focus areas of the journal are as follows: Biostatistics Clinical Trials Product Development and Innovation Global Perspectives Policy Regulatory Science Product Safety Special Populations
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