Department of interventional radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Interventional therapy center for oncology, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
Crit Rev Oncol Hematol. 2024 Dec;204:104522. doi: 10.1016/j.critrevonc.2024.104522. Epub 2024 Sep 26.
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.
对于晚期或不可切除的肝细胞癌（HCC）患者，需要安全有效的治疗方法来改善其长期预后。尽管指南推荐索拉非尼、仑伐替尼和阿替利珠单抗联合贝伐珠单抗（T+A）作为一线治疗，雷戈非尼作为二线治疗，但缺乏药物疗效比较，即没有推荐一种治疗方法作为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，系统评估和比较一线和二线治疗中不同治疗方案的总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和严重不良事件（SAE），这对临床决策和改善晚期 HCC 患者的预后至关重要。
我们检索了从数据库建立到 2022 年 5 月 23 日发表的评估不可切除或晚期 HCC 患者一线或二线治疗疗效或安全性的 III 期 RCT 研究。我们全面检索了 PubMed、Embase、Cochrane 图书馆和 Web of Science 四个数据库中的英文文献。我们感兴趣的结局包括 OS、PFS、ORR 和 SAE。通过列线图展示不同治疗方案之间的比较结果。绘制累积概率直方图，根据不同结局讨论治疗方案的排序概率。综合考虑各种治疗的有效性和安全性，绘制二维图指导临床实践。使用 R Studio 中的 Gemtc 包在贝叶斯框架中进行网络荟萃分析。
结果表明，HAIC-FO 在 OS、PFS 或 ORR 方面均优于 T+A 方案。TACE 联合仑伐替尼在 PFS 和 ORR 方面优于 T+A。除 T+A 方案外，信迪利单抗联合 IBI305 和卡瑞利珠单抗联合阿帕替尼也与更长的 OS、PFS 和 ORR 相关，且 SAE 发生率并不高于 T+A，尤其是卡瑞利珠单抗联合阿帕替尼，其安全性优于 T+A 方案。没有新的治疗方法或联合治疗比regorafenib 更有效。重要的是要注意，在 PFS 方面，阿帕替尼和卡博替尼的疗效与regorafenib 无统计学差异，因此在不能耐受regorafenib 或治疗失败的情况下，这两种治疗方法可作为替代治疗选择。
我们通过整合直接和间接比较的结果，进行了网络荟萃分析来评估多种治疗方式的疗效和安全性。本研究纳入了高质量的多中心 III 期 RCT，汇总和总结了一线和二线治疗中涉及的所有治疗方法，并分别与 T+A 和 regorafenib 进行比较，并根据疗效和安全性进行排名，以支持临床决策。
