Tan Darren Jun Hao, Tang Ansel Shao Pin, Lim Wen Hui, Ng Cheng Han, Nah Benjamin, Fu Clarissa, Xiao Jieling, Koh Benjamin, Tay Phoebe Wen Lin, Tan Eunice X, Teng Margaret, Syn Nicholas, Muthiah Mark D, Tamaki Nobuharu, Lee Sung Won, Kim Beom Kyung, Yau Thomas, Vogel Arndt, Loomba Rohit, Huang Daniel Q
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.
Liver Cancer. 2023 Mar 28;12(5):445-456. doi: 10.1159/000529824. eCollection 2023 Oct.
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.
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 ( < 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 ( < 0.001). There was minimal heterogeneity in the estimates for OS (all ≤ 33).
Survival outcomes for sorafenib in advanced HCC have improved over time. These data have important implications for clinical trial design.
新出现的数据表明，随着时间的推移，用索拉非尼治疗晚期肝细胞癌（HCC）的疗效可能有所改善。我们旨在提供索拉非尼治疗晚期HCC生存结局的可靠的事件发生时间估计。
在这项对随机对照试验（RCT）的系统评价和个体患者数据荟萃分析中，我们检索了从创刊至2022年9月的MEDLINE和Embase，以查找提供索拉非尼单药作为晚期HCC一线全身治疗的总生存期（OS）和无进展生存期（PFS）数据的RCT。我们使用从已发表的Kaplan-Meier曲线重建的个体参与者数据进行汇总分析，以获得OS和PFS的可靠估计。在识别出的1599篇文章中，29项研究（5525例患者）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随时间增加，从2015年之前研究中的9.8（95%CI：8.8-10.7）个月增加到2015年及以后研究中的13.4（95%CI：11.03-15.24）个月（P<0.001）。OS在试验阶段、地理区域或研究设计方面无差异。总体中位PFS为4.4（95%CI：3.9-4.8）个月，但PFS未随时间改善。对2015年及以后的研究进行敏感性分析以考虑直接作用抗病毒药物的引入，结果表明丙型肝炎病毒与死亡率降低相关（P<0.001）。OS估计值的异质性最小（均I²≤33）。
随着时间的推移，索拉非尼治疗晚期HCC的生存结局有所改善。这些数据对临床试验设计具有重要意义。
