Blinded independent central review versus local investigator assessment of PFS in RCTs of immunotherapy in advanced cancers: A systematic review and meta-analysis

IF 7.6 1区 医学 Q1 ONCOLOGY European Journal of Cancer Pub Date : 2024-10-20 DOI:10.1016/j.ejca.2024.115077
Simeone D’Ambrosio , Fabio Salomone , Filippo Vitale , Annarita Avanzo , Angela Viggiano , Luigi Liguori , Roberto Ferrara , Antonio Nuccio , Giuseppe Viscardi , Fabiana Napolitano , Antonio Santaniello , Luigi Formisano , Roberto Bianco , Alberto Servetto
{"title":"Blinded independent central review versus local investigator assessment of PFS in RCTs of immunotherapy in advanced cancers: A systematic review and meta-analysis","authors":"Simeone D’Ambrosio ,&nbsp;Fabio Salomone ,&nbsp;Filippo Vitale ,&nbsp;Annarita Avanzo ,&nbsp;Angela Viggiano ,&nbsp;Luigi Liguori ,&nbsp;Roberto Ferrara ,&nbsp;Antonio Nuccio ,&nbsp;Giuseppe Viscardi ,&nbsp;Fabiana Napolitano ,&nbsp;Antonio Santaniello ,&nbsp;Luigi Formisano ,&nbsp;Roberto Bianco ,&nbsp;Alberto Servetto","doi":"10.1016/j.ejca.2024.115077","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Assessment of Progression-free survival (PFS) events by investigators might be inaccurate in randomized controlled trials (RCTs) with open-label design. We explored differences in PFS evaluated by blinded independent central review (BICR) or local investigator assessment (IA) in trials testing immunotherapy (IO) in advanced cancers.</div></div><div><h3>Methods</h3><div>We systematically reviewed articles of RCTs investigating IO in advanced tumors, published in PubMed-indexed journals up to December 2023. For each RCT, we collected PFS results by BICR and by local IA. We calculated the discrepancy index (DI) as the ratio of BICR and IA Hazard Ratios (HR<sub>BICR</sub>/HR<sub>IA</sub>) for PFS. An overall DI and relative confidence interval (CI) were calculated using a fixed-effect model weighted for the inverse of variance.</div></div><div><h3>Findings</h3><div>Only 32/140 (22.9 %) RCTs reported both BICR and local IA PFS data, including 17,054 patients. PFS was the sole primary endpoint in 19/32 (59.4 %) and a co-primary endpoint 9/32 (28.2 %) trials. The study design was open label or double-blind in 17/32 (53.1 %) and 15/32 (46.9 %) RCTs, respectively. The overall DI was 1.07 (95 % CI 1.01–1.13; I<sup>2</sup> =0, p = 0.02), revealing a more optimistic analysis of results in favor of local IA. In the 17 open-label trials, the overall DI was 1.09 (95 % CI 1.02–1.17, I2 =0, p = 0.02), revealing a more favorable interpretation of PFS results by local investigators.</div></div><div><h3>Interpretation</h3><div>We found a statistically significant difference between BICR and local IA of PFS in trials of IO in cancer. These results suggest that the double assessment is recommended in RCTs testing IO, especially in open-label trials.</div></div><div><h3>Funding</h3><div>This work was supported by the <span>MFAG</span> <span><span>27826–2022</span></span> grant (Dr. Alberto Servetto).</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959804924012085","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Assessment of Progression-free survival (PFS) events by investigators might be inaccurate in randomized controlled trials (RCTs) with open-label design. We explored differences in PFS evaluated by blinded independent central review (BICR) or local investigator assessment (IA) in trials testing immunotherapy (IO) in advanced cancers.

Methods

We systematically reviewed articles of RCTs investigating IO in advanced tumors, published in PubMed-indexed journals up to December 2023. For each RCT, we collected PFS results by BICR and by local IA. We calculated the discrepancy index (DI) as the ratio of BICR and IA Hazard Ratios (HRBICR/HRIA) for PFS. An overall DI and relative confidence interval (CI) were calculated using a fixed-effect model weighted for the inverse of variance.

Findings

Only 32/140 (22.9 %) RCTs reported both BICR and local IA PFS data, including 17,054 patients. PFS was the sole primary endpoint in 19/32 (59.4 %) and a co-primary endpoint 9/32 (28.2 %) trials. The study design was open label or double-blind in 17/32 (53.1 %) and 15/32 (46.9 %) RCTs, respectively. The overall DI was 1.07 (95 % CI 1.01–1.13; I2 =0, p = 0.02), revealing a more optimistic analysis of results in favor of local IA. In the 17 open-label trials, the overall DI was 1.09 (95 % CI 1.02–1.17, I2 =0, p = 0.02), revealing a more favorable interpretation of PFS results by local investigators.

Interpretation

We found a statistically significant difference between BICR and local IA of PFS in trials of IO in cancer. These results suggest that the double assessment is recommended in RCTs testing IO, especially in open-label trials.

Funding

This work was supported by the MFAG 27826–2022 grant (Dr. Alberto Servetto).
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
晚期癌症免疫疗法 RCT 中对 PFS 的盲法独立中央审查与地方研究者评估:系统回顾与荟萃分析。
背景:在采用开放标签设计的随机对照试验(RCT)中,研究者对无进展生存期(PFS)事件的评估可能不准确。我们探讨了在晚期癌症免疫疗法(IO)试验中,通过盲法独立中央审查(BICR)或当地研究者评估(IA)对无进展生存期进行评估的差异:我们系统回顾了截至2023年12月发表在PubMed索引期刊上的研究晚期肿瘤IO的RCT文章。对于每项 RCT,我们都收集了 BICR 和当地 IA 的 PFS 结果。我们计算了差异指数(DI),即 BICR 和 IA 的 PFS 危险比(HRBICR/HRIA)。采用方差倒数加权的固定效应模型计算了总体差异指数和相对置信区间(CI):只有 32/140 项(22.9%)研究同时报告了 BICR 和局部 IA PFS 数据,包括 17,054 名患者。PFS是19/32(59.4%)项试验的唯一主要终点,也是9/32(28.2%)项试验的共同主要终点。17/32(53.1%)和15/32(46.9%)项RCT的研究设计分别为开放标签或双盲。总体DI为1.07 (95 % CI 1.01-1.13; I2 =0, p = 0.02),显示出更乐观的结果分析有利于局部IA。在17项开放标签试验中,总的DI为1.09(95 % CI 1.02-1.17,I2 =0,P = 0.02),显示当地研究者对PFS结果的解释更为有利:我们发现,在癌症 IO 试验中,BICR 和当地 IA 对 PFS 的判定在统计学上存在显著差异。这些结果表明,在进行IO试验的RCT中,尤其是在开放标签试验中,建议进行双重评估:这项工作得到了 MFAG27826-2022 基金(Alberto Servetto 博士)的支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
European Journal of Cancer
European Journal of Cancer 医学-肿瘤学
CiteScore
11.50
自引率
4.80%
发文量
953
审稿时长
23 days
期刊介绍: The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.
期刊最新文献
Shared decision-making supported by outcome information regarding surveillance after curative treatment for breast cancer: Results of the SHOUT-BC study Updated survival outcome of regorafenib, ipilimumab, and nivolumab in refractory microsatellite stable non-liver metastatic colorectal cancer: A phase I nonrandomized clinical trial Chinese herbal medicine (JianPi-BuShen) and completion rate of adjuvant chemotherapy for patients with stage II and III colon cancer: A randomized clinical trial Epidemiology of men with synchronous metastatic prostate cancer diagnosis – A nationwide 26-year temporal analysis Editorial Board
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1