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在实体瘤适应症的肿瘤药物关键试验中,研究者评估与盲态独立中央审查对客观缓解率的评估

Assessment of Objective Response Rate by Investigator vs. Blinded Independent Central Review in Pivotal Trials of Oncology Drugs for Solid Tumor Indications.

作者信息

Zettler Marjorie E

机构信息

Proclinical Staffing Inc., Philadelphia, PA 19123, USA.

出版信息

Cancers (Basel). 2025 Mar 25;17(7):1096. doi: 10.3390/cancers17071096.


DOI:10.3390/cancers17071096
PMID:40227586
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11987735/
Abstract

Objective response rate (ORR) is a surrogate endpoint frequently employed in early-phase clinical trials of anticancer agents for the treatment of solid tumors. Assessments of ORR by local investigators tend to be influenced by subjective factors, and blinded independent central review (BICR) is recommended by regulatory agencies in order to detect evaluation bias. The objective of this analysis was to compare BICR-assessed vs. investigator-assessed ORRs in pivotal trials of cancer drugs recently approved by the United States Food and Drug Administration (FDA) for solid tumor indications. The FDA's Novel Drug Approvals reports were reviewed to identify cancer therapies approved for solid tumor indications between 1 January 2020 and 30 June 2024. Among therapies with ORR as a primary endpoint in pivotal trials, and for which both BICR- and investigator-assessed ORRs were available, a pooled analysis was conducted to compare these ORRs (using the Mantel-Haenszel method). A correlation analysis was also performed to evaluate the concordance between ORR assessments. A total of 20 anticancer agents met the criteria for inclusion in this analysis, each supported by a single pivotal trial. Comparing BICR- and investigator-assessed ORRs in a pooled analysis did not identify any significant difference between the two assessments overall: OR = 0.98 (95% CI: 0.87-1.11), = 0.75, and I = 0%. The correlation analysis also revealed a high level of concordance between BICR- and investigator-assessed ORRs, with r = 0.96 ( < 0.05). This study found no evidence of evaluation bias in the assessment of ORR among registrational trials supporting recent FDA approvals of anticancer agents for solid tumor indications.

摘要

客观缓解率(ORR)是实体瘤抗癌药物早期临床试验中常用的替代终点。当地研究人员对ORR的评估往往受到主观因素的影响,监管机构建议采用盲法独立中央审查(BICR)以检测评估偏倚。本分析的目的是比较在美国食品药品监督管理局(FDA)近期批准的用于实体瘤适应症的癌症药物关键试验中,BICR评估的ORR与研究人员评估的ORR。回顾了FDA的新药批准报告,以确定2020年1月1日至2024年6月30日期间批准用于实体瘤适应症的癌症疗法。在关键试验中以ORR作为主要终点且同时有BICR和研究人员评估的ORR数据的疗法中,进行了汇总分析以比较这些ORR(采用Mantel-Haenszel方法)。还进行了相关性分析以评估ORR评估之间的一致性。共有20种抗癌药物符合纳入本分析的标准,每种药物均有一项关键试验支持。在汇总分析中比较BICR和研究人员评估的ORR时,未发现两种评估之间存在总体显著差异:OR = 0.98(95% CI:0.87 - 1.11),P = 0.75,I² = 0%。相关性分析还显示BICR和研究人员评估的ORR之间具有高度一致性,r = 0.96(P < 0.05)。本研究未发现支持FDA近期批准用于实体瘤适应症的抗癌药物的注册试验中在ORR评估方面存在评估偏倚的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27eb/11987735/fff41ba105ec/cancers-17-01096-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27eb/11987735/4b348010e4e6/cancers-17-01096-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27eb/11987735/3d43b095d284/cancers-17-01096-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27eb/11987735/fff41ba105ec/cancers-17-01096-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27eb/11987735/4b348010e4e6/cancers-17-01096-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27eb/11987735/3d43b095d284/cancers-17-01096-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27eb/11987735/fff41ba105ec/cancers-17-01096-g003.jpg

相似文献

[1]
Assessment of Objective Response Rate by Investigator vs. Blinded Independent Central Review in Pivotal Trials of Oncology Drugs for Solid Tumor Indications.

Cancers (Basel). 2025-3-25

[2]
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[3]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Cancer statistics, 2025.

CA Cancer J Clin. 2025

[2]
Dose Optimization of Targeted Therapies for Oncologic Indications.

Cancers (Basel). 2024-6-9

[3]
Clinical trial design and treatment effects: a meta-analysis of randomised controlled and single-arm trials supporting 437 FDA approvals of cancer drugs and indications.

BMJ Evid Based Med. 2024-9-20

[4]
Objective response rate and progression-free survival as surrogates for overall survival treatment effect: A meta-analysis across diverse tumour groups and contemporary therapies.

Eur J Cancer. 2024-2

[5]
Detection bias in open-label trials of anticancer drugs: a meta-epidemiological study.

BMJ Evid Based Med. 2023-11-22

[6]
FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications: cross sectional analysis.

BMJ. 2023-5-9

[7]
Irreconcilable Differences: The Divorce Between Response Rates, Progression-Free Survival, and Overall Survival.

J Clin Oncol. 2023-5-20

[8]
Meta-Analysis of 49 Roche Oncology Trials Comparing Blinded Independent Central Review (BICR) and Local Evaluation to Assess the Value of BICR.

Oncologist. 2024-8-5

[9]
Use of Single-Arm Trials for US Food and Drug Administration Drug Approval in Oncology, 2002-2021.

JAMA Oncol. 2023-2-1

[10]
Local Investigators Significantly Overestimate Overall Response Rates Compared to Blinded Independent Central Reviews in Uncontrolled Oncology Trials: A Comprehensive Review of the Literature.

Front Pharmacol. 2022-5-16

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