Adjuvant chemotherapy compared to observation in resected biliary tract cancers: Survival meta-analysis of phase-III randomized controlled trials

IF 7.6 1区 医学 Q1 ONCOLOGY European Journal of Cancer Pub Date : 2025-03-07 DOI:10.1016/j.ejca.2025.115342
Erman Akkus , Angela Lamarca
{"title":"Adjuvant chemotherapy compared to observation in resected biliary tract cancers: Survival meta-analysis of phase-III randomized controlled trials","authors":"Erman Akkus ,&nbsp;Angela Lamarca","doi":"10.1016/j.ejca.2025.115342","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>A limited number of randomized controlled trials (RCTs) investigated adjuvant chemotherapy in biliary tract cancers (BTCs). Recurrences and deaths are common in the first 2 years and survival remains poor despite adjuvant treatment.</div></div><div><h3>Methods</h3><div>Phase-III RCTs were included comparing adjuvant chemotherapy and observation in resected BTCs. The primary endpoints were recurrence-free (RFS) and overall survival (OS). Proportional hazard results were used for trial-based analyses. Patient data was curated from published Kaplan-Meier curves to analyze short-term (2-year) hazards. The Parmar and generic inverse variance methods were used.</div></div><div><h3>Results</h3><div>1308 patients in 4 trials (BILCAP, ASCOT, BCAT, PRODIGE-12) were included. Capecitabine (BILCAP) and S-1 (ASCOT) were grouped as 5-FU-based, gemcitabine (BCAT) and gemcitabine-oxaliplatin (PRODIGE-12) were grouped as gemcitabine-based chemotherapy. Adjuvant 5FU-based chemotherapy improved RFS [HR: 0.80 (95 % CI:0.68–0.95), p = 0.012] and OS [HR: 0.78 (95 % CI:0.65–0.94), p = 0.009]. However, gemcitabine-based chemotherapy did not provide benefit in RFS [HR: 0.90 (95 % CI:0.70–1.15), p = 0.428] and OS [HR: 1.03 (95 % CI:0.78–1.36), p = 0.794]. The benefit of 5-FU-based chemotherapy was more apparent in the short-term (2-year hazards) (RFS: [HR: 0.67 (95 %CI:57–0.79), p &lt; 0.001] and OS: [HR: 0.61 (95 % CI:59–0.64), p &lt; 0.001]). However, gemcitabine-based chemotherapy did not provide RFS benefit in the short term either [HR: 0.80 (95 % CI:0.64–0.1.01), p = 0.067] and seemed to be even detrimental for OS [HR: 1.22 (95 % CI:1.14–1.31), p &lt; 0.001] in the first 2 years.</div></div><div><h3>Conclusion</h3><div>This study confirms using 5FU-based monotherapy in the adjuvant treatment of resected BTCs. The more prominent benefit in the first 2 years emphasizes that more effective adjuvant treatments with sustained long-term benefits are needed. Two-year proportional hazards OS and RFS are proposed here as an additional secondary end-point to consider in future clinical trials. in this setting.</div><div>Registration ID (PROSPERO): CRD42024614444</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115342"},"PeriodicalIF":7.6000,"publicationDate":"2025-03-07","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/S0959804925001236","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

A limited number of randomized controlled trials (RCTs) investigated adjuvant chemotherapy in biliary tract cancers (BTCs). Recurrences and deaths are common in the first 2 years and survival remains poor despite adjuvant treatment.

Methods

Phase-III RCTs were included comparing adjuvant chemotherapy and observation in resected BTCs. The primary endpoints were recurrence-free (RFS) and overall survival (OS). Proportional hazard results were used for trial-based analyses. Patient data was curated from published Kaplan-Meier curves to analyze short-term (2-year) hazards. The Parmar and generic inverse variance methods were used.

Results

1308 patients in 4 trials (BILCAP, ASCOT, BCAT, PRODIGE-12) were included. Capecitabine (BILCAP) and S-1 (ASCOT) were grouped as 5-FU-based, gemcitabine (BCAT) and gemcitabine-oxaliplatin (PRODIGE-12) were grouped as gemcitabine-based chemotherapy. Adjuvant 5FU-based chemotherapy improved RFS [HR: 0.80 (95 % CI:0.68–0.95), p = 0.012] and OS [HR: 0.78 (95 % CI:0.65–0.94), p = 0.009]. However, gemcitabine-based chemotherapy did not provide benefit in RFS [HR: 0.90 (95 % CI:0.70–1.15), p = 0.428] and OS [HR: 1.03 (95 % CI:0.78–1.36), p = 0.794]. The benefit of 5-FU-based chemotherapy was more apparent in the short-term (2-year hazards) (RFS: [HR: 0.67 (95 %CI:57–0.79), p < 0.001] and OS: [HR: 0.61 (95 % CI:59–0.64), p < 0.001]). However, gemcitabine-based chemotherapy did not provide RFS benefit in the short term either [HR: 0.80 (95 % CI:0.64–0.1.01), p = 0.067] and seemed to be even detrimental for OS [HR: 1.22 (95 % CI:1.14–1.31), p < 0.001] in the first 2 years.

Conclusion

This study confirms using 5FU-based monotherapy in the adjuvant treatment of resected BTCs. The more prominent benefit in the first 2 years emphasizes that more effective adjuvant treatments with sustained long-term benefits are needed. Two-year proportional hazards OS and RFS are proposed here as an additional secondary end-point to consider in future clinical trials. in this setting.
Registration ID (PROSPERO): CRD42024614444
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
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
Editorial Board Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study Adjuvant chemotherapy compared to observation in resected biliary tract cancers: Survival meta-analysis of phase-III randomized controlled trials Retrieval-Augmented Generation: Advancing personalized care and research in oncology AI integrations with lung cancer screening: Considerations in developing AI in a public health setting
×
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