Balancing Efficacy and Tolerability of First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis.

IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver Cancer Pub Date : 2023-07-25 eCollection Date: 2024-04-01 DOI:10.1159/000531744
Ciro Celsa, Giuseppe Cabibbo, David James Pinato, Gabriele Di Maria, Marco Enea, Marco Vaccaro, Salvatore Battaglia, Giacomo Emanuele Maria Rizzo, Paolo Giuffrida, Carmelo Marco Giacchetto, Gabriele Rancatore, Maria Vittoria Grassini, Calogero Cammà
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Abstract

Background: Atezolizumab + bevacizumab represent the current standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, direct comparison with other combination treatments including immune checkpoint inhibitors (ICI) + tyrosine kinase inhibitors (TKIs) are lacking.

Objectives: This network meta-analysis (NMA) aims to indirectly compare the efficacy and the safety of first-line systemic therapies for unresectable advanced HCC.

Method: A literature search of MEDLINE, Embase, and SCOPUS databases was conducted up to October 31, 2022. Phase 3 randomized controlled trials (RCTs) testing TKIs, including sorafenib and lenvatinib, or ICIs reporting overall survival (OS) and progression-free survival (PFS) were included. Individual survival data were extracted from OS and PFS curves to calculate restricted mean survival time. A Bayesian NMA was performed to compare treatments in terms of efficacy (15- and 30-month OS, 6-month PFS) and safety, represented by grade ≥3 (severe) adverse events (SAEs). The incremental safety-effectiveness ratio as measure of net health benefit was calculated as the difference in SAE probability divided by survival difference between the 2 most effective treatments.

Results: Nine RCTs enrolling 6,600 patients were included. Atezolizumab plus bevacizumab showed the highest probability (88%) of achieving the 30-month OS landmark. Lenvatinib showed a probability of 86% of achieving best PFS outcomes. ICI monotherapies ranked as most tolerable. Atezolizumab plus bevacizumab showed the best net health benefit for OS, compared to durvalumab plus tremelimumab. When evaluating the net health benefit for PFS, at a willingness-to-risk threshold of 10% of SAEs for life-month gained, atezolizumab plus bevacizumab was favoured in 78% of cases, while at threshold of 30% of SAEs for life-month gained, lenvatinib was favoured in 76% of cases.

Conclusions: Atezolizumab plus bevacizumab is the best treatment in terms of net benefit and therefore it should be recommended as standard of care. Compared to atezolizumab plus bevacizumab, lenvatinib monotherapy had the best net benefit for PFS when physicians and patients are available to accept a higher risk of toxicity.

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平衡晚期肝细胞癌一线系统疗法的疗效和耐受性:一项网络 Meta 分析。
背景:阿特珠单抗+贝伐单抗是目前一线治疗晚期肝细胞癌(HCC)的标准疗法。然而,目前还缺乏与其他联合疗法(包括免疫检查点抑制剂(ICI)+酪氨酸激酶抑制剂(TKIs))的直接比较:本网络荟萃分析(NMA)旨在间接比较不可切除晚期HCC一线系统疗法的疗效和安全性:方法:对截至2022年10月31日的MEDLINE、Embase和SCOPUS数据库进行文献检索。方法:检索了截至2022年10月31日的MEDLINE、Embed和SCOPUS数据库中的文献,包括测试索拉非尼、来伐替尼等TKIs或报告总生存期(OS)和无进展生存期(PFS)的ICIs的3期随机对照试验(RCT)。从OS和PFS曲线中提取单个生存数据,计算限制性平均生存时间。进行了贝叶斯NMA,以比较各种疗法的疗效(15个月和30个月OS、6个月PFS)和安全性(以≥3级(严重)不良事件(SAE)表示)。作为衡量净健康获益的增量安全有效性比的计算方法是:SAE概率的差异除以两种最有效疗法的生存期差异:结果:共纳入了9项研究,6,600名患者接受了治疗。阿特珠单抗加贝伐单抗达到30个月OS里程碑的概率最高(88%)。伦伐替尼实现最佳PFS结果的概率为86%。ICI 单一疗法的耐受性最好。与durvalumab加tremelimumab相比,Atezolizumab加贝伐单抗在OS方面显示出最佳的净健康效益。在评估PFS的净健康获益时,以10%的SAEs为生命月获益的风险意愿阈值,78%的病例选择了阿特珠单抗加贝伐单抗,而以30%的SAEs为生命月获益的风险意愿阈值,76%的病例选择了来伐替尼:结论:就净获益而言,阿特珠单抗联合贝伐单抗是最佳治疗方案,因此应将其推荐为标准治疗方案。与阿特珠单抗联合贝伐珠单抗相比,在医生和患者都能接受较高毒性风险的情况下,来伐替尼单药治疗的净疗效最好。
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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.
期刊最新文献
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