Efficacy and Safety of Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis of Phase III Trials
Efficacy and Safety of Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis of Phase III Trials
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DOI：
10.1159/000481314
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发表时间：
2017-01-01
期刊：
影响因子：
13.8
通讯作者：
Bolondi, Luigi
中科院分区：
文献类型：
--
作者：
Cucchetti, Alessandro;Piscaglia, Fabio;Bolondi, Luigi
目的/背景：索拉非尼治疗晚期肝细胞癌（HCC）后，不同的研究试图评估其他全身治疗是否可以提高生存率。为了提供新药疗效和安全性的全面间接治疗比较，对III期随机对照试验进行了网络荟萃分析（NMA）。研究方法：截至2016年11月1日的相关文献检索后，6项研究符合分析条件，包括4，812例晚期HCC患者：2，454例接受索拉非尼，577例接受布立尼布，530例接受舒尼替尼，514例接受利尼法尼，358例接受索拉非尼+厄洛替尼，379例接受安慰剂。频率主义NMA用于在单一分析框架内比较治疗。结果如下：NMA显示，单独的索拉非尼，无论与厄洛替尼的组合如何，和利尼法尼相比于安慰剂提供显著的生存优势（p < 0.05），但彼此之间没有任何显著差异。相反，与安慰剂相比，所有方案均显著改善无进展生存期（p < 0.05）。疗效等级顺序为：索拉非尼+/-厄洛替尼、利尼法尼、布立尼布、舒尼替尼和安慰剂。索拉非尼+/-厄洛替尼是需要停止治疗的不良事件数量最少的方案，而利尼法尼和布立尼布导致最多的不良事件。风险-获益总结确定了一组在疗效和安全性之间具有相似平衡的治疗，其中包括索拉非尼单药治疗或索拉非尼与厄洛替尼联合治疗，同时具有最高的疗效和安全性。结论：索拉非尼仍然是晚期HCC的最佳全身治疗;与安慰剂相比，利尼法尼也具有生存优势，但安全性较低。(C)2017 S. Karger AG，巴塞尔
Aim/Background: After the introduction of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC), different studies tried to evaluate whether other systemic therapies can improve survival. To provide a comprehensive indirect treatment comparison of efficacy and safety of novel drugs, a network meta-analysis (NMA) of phase III randomized controlled trials was performed. Methods: After pertinent literature search up to November 1, 2016, 6 studies were eligible for the analysis including 4,812 individual patients with advanced HCC: 2,454 received sorafenib, 577 received brivanib, 530 received sunitinib, 514 received linifanib, 358 received sorafenib + erlotinib and 379 received placebo. Frequentist NMA was used to compare treatments within a single analytical framework. Results: NMA showed that sorafenib alone, regardless of combination with erlotinib, and linifanib provide a significant survival advantage over placebo (p < 0.05) but without any significant difference between each other. Conversely, all regimens significantly ameliorate progression-free survival versus placebo (p < 0.05). The rank order of efficacy was: sorafenib +/- erlotinib, linifanib, brivanib, sunitinib, and placebo. Sorafenib +/- erlotinib was the regimen with the fewest number of adverse events that required discontinuation of treatment, whereas linifanib and brivanib resulted in the most adverse events. The risk-benefit summary identified one cluster of therapies with a similar balance between efficacy and safety which included sorafenib alone or in combination with erlotinib, having, at the same time, the highest efficacy and safety. Conclusions: Sorafenib remains the best systemic treatment for advanced HCC; linifanib also resulted in survival advantages over placebo but with a lower safety profile. (C) 2017 S. Karger AG, Basel