对于晚期或不可切除的肝细胞癌（HCC）患者，迫切需要安全有效的治疗来改善其长期预后。虽然指南推荐一线治疗如索拉非尼、仑伐替尼、阿特珠单抗联合贝伐珠单抗（T A）和二线治疗如瑞戈非尼，但缺乏药物之间的疗效比较，即不推荐一种治疗作为针对特定患者群体的最佳或替代选择。因此，我们将基于III期随机对照试验（RCT）进行高质量的网络荟萃分析，系统评估和比较总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和一线和二线治疗中不同治疗方案的严重不良事件（SAE），这对于晚期 HCC 患者的临床决策和预后改善至关重要。感兴趣的研究是评估疗效或疗效的 III 期随机对照试验不可切除或晚期 HCC 患者一线或二线治疗的安全性。对 PubMed、Embase、Cochrane Library 和 Web of Science 四个数据库中以英文发表的文献从建库到 2022 年 5 月 23 日进行了全面检索。感兴趣的结果包括 OS、PFS、ORR 和 SAE。开发了一个排行榜来显示不同处理之间的比较结果。绘制累积概率直方图来讨论基于不同结果的治疗排序概率。综合考虑各种治疗的有效性和安全性，绘制二维图来指导临床实践。使用R Studio中的Gemtc包在贝叶斯框架下进行网络荟萃分析。结果显示，无论OS、PFS或ORR，HAIC-FO均优于TA方案。 TACE 联合乐伐替尼在 PFS 和 ORR 方面的表现优于 T A。除TA方案外，信迪利单抗联合IBI305、卡瑞利珠单抗联合阿帕替尼也与较长的OS、PFS和ORR相关，且其SAE发生率不高于TA，特别是卡瑞利珠单抗联合阿帕替尼，其安全性为优于TA方案。没有比瑞戈非尼更有效的新疗法或组合。值得注意的是，对于PFS，阿帕替尼和卡博替尼的疗效与瑞戈非尼的疗效没有统计学差异，因此这两种治疗方法可以作为瑞戈非尼不耐受或治疗失败的情况下的替代治疗选择。我们进行了一个网络研究荟萃分析通过整合直接和间接比较的结果来评估多种治疗方式的有效性和安全性。该研究纳入了高质量的多中心 III 期随机对照试验，整理和总结了一线和二线治疗中涉及晚期或不可切除 HCC 的所有治疗方法，并分别与 T A 和瑞格非尼进行比较，并根据疗效和安全性进行排名，以支持临床决策。版权所有 © 2024 Elsevier B.V. 保留所有权利。

For patients with advanced or unresectable hepatocellular carcinoma (HCC), safe and effective therapies are urgently needed to improve their long-term prognosis. Although the guidelines recommend first-line treatments such as sorafenib, lenvatinib, and atezolizumab in combination with bevacizumab (T+A) and second-line treatments such as regorafenib, the efficacy comparison between drugs is lacking, that is, a treatment is not recommended as the optimal or alternative choice for a specific patient population. Therefore, we will conduct a high-quality network meta-analysis based on Phase III randomized controlled trials (RCTs) to systematically evaluate and compare overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and serious adverse events (SAE) of different treatment protocols in the context of first-line and second-line therapies, which are critical for clinical decision making and prognostic improvement in advanced HCC patients.The studies of interest were Phase III RCTs evaluating the efficacy or safety of first- or second-line therapies in patients with unresectable or advanced HCC. Literature published in English from the four databases of PubMed, Embase, Cochrane Library, and Web of Science was comprehensively searched from the inception to May 23, 2022. Outcomes of interest included OS, PFS, ORR, and SAE. A league table was developed to show the results of the comparison between different treatments. A histogram of cumulative probability was drawn to discuss the ranking probability of treatments based on different outcomes. The effectiveness and safety of various treatments were comprehensively considered and the two-dimensional diagram was plotted to guide clinical practice. The Gemtc package in R Studio was used for network meta-analysis in a Bayesian framework.The results showed that HAIC-FO was superior to T+A regimen, regardless of OS, PFS or ORR. TACE combined with lenvatinib performed better than T+A in PFS, and ORR. In addition to the T+A regimen, Sintilimab combined with IBI305 and camrelizumab combined with apatinib were also associated with longer OS, PFS, and ORR, and their SAE incidence was not higher than that of T+A, especially for camrelizumab combined with apatinib, its safety was better than that of T+A regimen. There were no new treatments or combinations that were more effective than regorafenib. It was important to note that for PFS, the efficacy of apatinib and cabozantinib was not statistically different from that of regorafenib, so these two treatments could be used as alternative treatment options in cases where regorafenib was not tolerated or treatment failed.We conducted a network meta-analysis to evaluate the efficacy and safety of multiple treatment modalities by integrating the results of direct and indirect comparisons. This study included high-quality multicenter Phase III RCTs, collated and summarized all treatments involved in advanced or unresectable HCC in first-line and second-line settings, and compared with T+A and regorafenib, respectively, and ranked based on efficacy and safety to support clinical decision making.Copyright © 2024 Elsevier B.V. All rights reserved.