Background: Emerging data suggest that outcomes for advanced hepatocellular carcinoma (HCC) treated with sorafenib may have improved over time. We aimed to provide robust, time-to-event estimates of survival outcomes for sorafenib in advanced HCC. Summary: In this systematic review and individual patient data meta-analysis of randomized-controlled trials (RCTs), we searched MEDLINE and Embase from inception till September 2022 for RCTs that provided data for overall survival (OS) and progression-free survival (PFS) for sorafenib monotherapy as first-line systemic therapy for advanced HCC. We performed a pooled analysis using reconstructed individual participant data from published Kaplan-Meier curves to obtain robust estimates for OS and PFS. Of 1,599 articles identified, 29 studies (5,525 patients) met the inclusion criteria. Overall, the median OS was 10.4 (95% CI 9.6 – 11.4) months. Median OS increased over time, from 9.8 (95% CI 8.8¬ – 10.7) months in studies before 2015, to 13.4 (95% CI 11.03 – 15.24) months in studies from 2015 onwards, p<0.001. OS did not differ by trial phase, geographical region, or study design. The overall median PFS was 4.4 (95% CI 3.9 – 4.8) months, but PFS did not improve over time. Sensitivity analysis of studies from 2015 and onwards to account for the introduction of direct-acting antivirals determined that hepatitis C virus was associated with reduced mortality (p<0.001). There was minimal heterogeneity in the estimates for OS (all I2 ≤ 33). Key Messages: Survival outcomes for sorafenib in advanced HCC have improved over time. These data have important implications for clinical trial design.


中文翻译：

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索拉非尼治疗晚期肝细胞癌的生存趋势：随机试验的重建个体患者数据荟萃分析


背景：新数据表明，随着时间的推移，索拉非尼治疗晚期肝细胞癌（HCC）的结果可能有所改善。我们的目的是对索拉非尼治疗晚期 HCC 的生存结果提供可靠的、事件发生时间的估计。摘要：在这项随机对照试验 (RCT) 的系统回顾和个体患者数据荟萃分析中，我们搜索了 MEDLINE 和 Embase 从开始到 2022 年 9 月的随机对照试验，这些随机对照试验提供了总生存期 (OS) 和无进展生存期 (PFS) 的数据）索拉非尼单药治疗作为晚期 HCC 的一线全身治疗。我们使用已发布的 Kaplan-Meier 曲线中重建的个体参与者数据进行了汇总分析，以获得 OS 和 PFS 的可靠估计。在确定的 1,599 篇文章中，29 项研究（5,525 名患者）符合纳入标准。总体而言，中位 OS 为 10.4 (95% CI 9.6 – 11.4) 个月。中位 OS 随着时间的推移而增加，从 2015 年之前的研究中的 9.8 (95% CI 8.8-10.7) 个月增加到 2015 年以后的研究中的 13.4 (95% CI 11.03 – 15.24) 个月，p<0.001。 OS 因试验阶段、地理区域或研究设计而异。总体中位 PFS 为 4.4 (95% CI 3.9 – 4.8) 个月，但 PFS 并未随着时间的推移而改善。对 2015 年及以后引入直接作用抗病毒药物的研究进行的敏感性分析确定，丙型肝炎病毒与死亡率降低相关 (p<0.001)。 OS 估计值的异质性极小（所有 I2 ≤ 33）。关键信息：索拉非尼治疗晚期 HCC 的生存结果随着时间的推移有所改善。这些数据对临床试验设计具有重要意义。