First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Systematic Review and Patient-Level Network Meta-Analysis.

IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Liver Cancer Pub Date : 2022-08-23 eCollection Date: 2023-02-01 DOI:10.1159/000526639
Khi Yung Fong, Joseph Jonathan Zhao, Rehena Sultana, Joycelyn Jie Xin Lee, Suat Ying Lee, Stephen Lam Chan, Thomas Yau, David Wai Meng Tai, Raghav Sundar, Chow Wei Too
{"title":"First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Systematic Review and Patient-Level Network Meta-Analysis.","authors":"Khi Yung Fong, Joseph Jonathan Zhao, Rehena Sultana, Joycelyn Jie Xin Lee, Suat Ying Lee, Stephen Lam Chan, Thomas Yau, David Wai Meng Tai, Raghav Sundar, Chow Wei Too","doi":"10.1159/000526639","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Sorafenib was historically the standard of care for advanced hepatocellular carcinoma (aHCC) until it was superseded by the combination of atezolizumab and bevacizumab. Thereafter, several novel first-line combination therapies have demonstrated favorable outcomes. The efficacies of these treatments in relation to current and previous standards of care are unknown, necessitating an overarching evaluation.</p><p><strong>Methods: </strong>A systematic literature search was conducted on PubMed, EMBASE, Scopus, and the Cochrane Controlled Register of Trials for phase III randomized controlled trials investigating first-line systemic therapies for aHCC. Kaplan-Meier curves for overall survival (OS) and progression-free survival (PFS) were graphically reconstructed to retrieve individual patient-level data. Derived hazard ratios (HRs) for each study were pooled in a random-effects network meta-analysis (NMA). NMAs were also conducted using study-level HRs for various subgroups, according to viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion, and extrahepatic spread. Treatment strategies were ranked using <i>p</i> scores.</p><p><strong>Results: </strong>Among 4,321 articles identified, 12 trials and 9,589 patients were included for analysis. Only two therapies showed OS benefit over sorafenib: combined anti-programmed-death and anti-VEGF pathway inhibitor monoclonal antibodies (Anti-PD-(L)1/VEGF Ab), including atezolizumab-bevacizumab and sintilimab-bevacizumab biosimilar (HR = 0.63, 95% CI = 0.53-0.76) and tremelimumab-durvalumab (HR = 0.78, 95% CI = 0.66-0.92). Anti-PD-(L)1/VEGF Ab showed OS benefit over all other therapies except tremelimumab-durvalumab. Low heterogeneity (<i>I</i><sup>2</sup> = 0%) and inconsistency (Cochran's <i>Q</i> = 0.52, <i>p</i> = 0.773) was observed. <i>p</i> scores for OS ranked Anti-PD-(L)1/VEGF Ab as the best treatment in all subgroups, except hepatitis B where atezolizumab-cabozantinib ranked highest for both OS and PFS, as well as nonviral HCC and AFP ≥400 μg/L where tremelimumab-durvalumab ranked highest for OS.</p><p><strong>Conclusion: </strong>This NMA supports Anti-PD-(L)1/VEGF Ab as the first-line therapy for aHCC and demonstrates a comparable benefit for tremelimumab-durvalumab which also extends to certain subgroups. Results of the subgroup analysis may guide treatment according to baseline characteristics, while pending further studies.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 1","pages":"7-18"},"PeriodicalIF":11.6000,"publicationDate":"2022-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/47/lic-0012-0007.PMC9982345.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000526639","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/2/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: Sorafenib was historically the standard of care for advanced hepatocellular carcinoma (aHCC) until it was superseded by the combination of atezolizumab and bevacizumab. Thereafter, several novel first-line combination therapies have demonstrated favorable outcomes. The efficacies of these treatments in relation to current and previous standards of care are unknown, necessitating an overarching evaluation.

Methods: A systematic literature search was conducted on PubMed, EMBASE, Scopus, and the Cochrane Controlled Register of Trials for phase III randomized controlled trials investigating first-line systemic therapies for aHCC. Kaplan-Meier curves for overall survival (OS) and progression-free survival (PFS) were graphically reconstructed to retrieve individual patient-level data. Derived hazard ratios (HRs) for each study were pooled in a random-effects network meta-analysis (NMA). NMAs were also conducted using study-level HRs for various subgroups, according to viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion, and extrahepatic spread. Treatment strategies were ranked using p scores.

Results: Among 4,321 articles identified, 12 trials and 9,589 patients were included for analysis. Only two therapies showed OS benefit over sorafenib: combined anti-programmed-death and anti-VEGF pathway inhibitor monoclonal antibodies (Anti-PD-(L)1/VEGF Ab), including atezolizumab-bevacizumab and sintilimab-bevacizumab biosimilar (HR = 0.63, 95% CI = 0.53-0.76) and tremelimumab-durvalumab (HR = 0.78, 95% CI = 0.66-0.92). Anti-PD-(L)1/VEGF Ab showed OS benefit over all other therapies except tremelimumab-durvalumab. Low heterogeneity (I2 = 0%) and inconsistency (Cochran's Q = 0.52, p = 0.773) was observed. p scores for OS ranked Anti-PD-(L)1/VEGF Ab as the best treatment in all subgroups, except hepatitis B where atezolizumab-cabozantinib ranked highest for both OS and PFS, as well as nonviral HCC and AFP ≥400 μg/L where tremelimumab-durvalumab ranked highest for OS.

Conclusion: This NMA supports Anti-PD-(L)1/VEGF Ab as the first-line therapy for aHCC and demonstrates a comparable benefit for tremelimumab-durvalumab which also extends to certain subgroups. Results of the subgroup analysis may guide treatment according to baseline characteristics, while pending further studies.

Abstract Image

Abstract Image

Abstract Image

晚期肝细胞癌的一线系统疗法:系统综述和患者层面的网络荟萃分析。
简介索拉非尼一直是治疗晚期肝细胞癌(aHCC)的标准疗法,直到被阿特珠单抗和贝伐单抗联合疗法所取代。此后,几种新型一线联合疗法取得了良好的疗效。这些疗法的疗效与当前和以往的治疗标准相比尚不清楚,因此有必要进行总体评估:方法:在PubMed、EMBASE、Scopus和Cochrane对照试验登记册上进行了系统性文献检索,以了解研究治疗aHCC一线系统疗法的III期随机对照试验。对总生存期(OS)和无进展生存期(PFS)的卡普兰-梅耶曲线进行图形重构,以检索患者个体水平的数据。在随机效应网络荟萃分析(NMA)中对每项研究得出的危险比(HRs)进行汇总。根据病毒病因学、巴塞罗那临床肝癌(BCLC)分期、甲胎蛋白(AFP)水平、大血管侵犯和肝外播散等因素,还使用不同亚组的研究水平HR进行了NMA分析。治疗策略采用P评分进行排序:在4321篇文章中,有12项试验和9589名患者被纳入分析。与索拉非尼相比,只有两种疗法显示出OS获益:联合抗程序性死亡和抗血管内皮生长因子通路抑制剂单克隆抗体(Anti-PD-(L)1/VEGF Ab),包括atezolizumab-bevacizumab和sintilimab-bevacizumab生物类似物(HR = 0.63,95% CI = 0.53-0.76)以及tremelimumab-durvalumab(HR = 0.78,95% CI = 0.66-0.92)。除tremelimumab-durvalumab外,抗PD-(L)1/VEGF抗体的OS获益优于所有其他疗法。观察到低异质性(I2 = 0%)和不一致性(Cochran's Q = 0.52,p = 0.773)。OS的p得分将Anti-PD-(L)1/VEGF Ab列为所有亚组的最佳治疗方法,但乙型肝炎除外,atezolizumab-cabozantinib的OS和PFS均排名第一,非病毒性HCC和AFP≥400 μg/L的tremelimumab-durvalumab的OS排名第一:该NMA支持将抗-PD-(L)1/VEGF抗体作为治疗HCC的一线疗法,并证明了tremelimumab-durvalumab也能为某些亚组带来类似的获益。亚组分析结果可根据基线特征指导治疗,但仍有待进一步研究。
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 求助全文
来源期刊
Liver Cancer
Liver Cancer Medicine-Oncology
CiteScore
20.80
自引率
7.20%
发文量
53
审稿时长
16 weeks
期刊介绍: Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信