背景:尽管在过去的十年中,肝细胞癌(HCC)的治疗方案取得了显着进展,整体预后不佳仍然困扰着HCC患者。已经进行了几项比较试验,以研究经肝动脉化疗栓塞(TACE)是否可以改善接受索拉非尼治疗晚期HCC的患者的临床结局;然而,调查结果不一致。
目的:研究索拉非尼联合TACE与索拉非尼单独治疗晚期肝癌的潜在协同作用和安全性,通过进行系统评价和荟萃分析。
方法:本研究遵循PRISMA声明。使用Cochrane图书馆进行了系统的文献检索,Embase,PubMed,和WebofScience数据库。本工作中包括的数据是从接受索拉非尼联合TACE或索拉非尼单独治疗的晚期HCC患者中收集的。使用ReviewManager软件进行数据合成和荟萃分析。
结果:本研究包括来自5项比较临床试验(1项为随机对照试验,4项为回顾性研究)的2780名患者。结果发现,接受索拉非尼联合TACE治疗的患者在总生存期(OS)方面有更好的预后,合并风险比(HR)为0.65[95%置信区间(95CI):0.46-0.93,P=0.02,n=2780]。始终如一,索拉非尼加TACE组和索拉非尼组的无进展生存期(PFS)和进展时间(TTP)存在显著差异(PFS:HR=0.62,95CI:0.40~0.96,P=0.03,n=443;TTP:HR=0.73,95CI:0.64~0.83,P<0.00001,n=2451).通过联合治疗,疾病控制率(DCR)也显着增加(风险比=1.36,95CI:1.02-1.81,P=0.04,n=641)。关于安全,任何不良事件(AE)的发生率由于添加TACE而增加;然而,≥3级AE无显著差异。
结论:索拉非尼联合TACE的疗效优于索拉非尼单药治疗,正如延长的操作系统所证明的那样,PFS,和TTP,以及增加DCR。其他高质量的试验对于进一步验证这种联合治疗晚期HCC的临床益处至关重要。
BACKGROUND: Although the past decade has seen remarkable advances in treatment options for hepatocellular carcinoma (HCC), the dismal overall prognosis still envelops HCC patients. Several comparative trials have been conducted to study whether transarterial chemoembolization (TACE) could improve clinical outcomes in patients receiving sorafenib for advanced HCC; however, the findings have been inconsistent.
OBJECTIVE: To study the potential synergies and safety of sorafenib plus TACE vs sorafenib alone for treating advanced HCC, by performing a systematic
review and meta-analysis.
METHODS: This study was conducted following the PRISMA statement. A systematic literature search was conducted using the Cochrane Library, Embase, PubMed, and Web of Science databases. Data included in the present work were collected from patients diagnosed with advanced HCC receiving sorafenib plus TACE or sorafenib alone. Data synthesis and meta-analysis were conducted using
Review Manager software.
RESULTS: The present study included 2780 patients from five comparative clinical trials (1 was randomized control trial and 4 were retrospective studies). It was found that patients receiving sorafenib plus TACE had better prognoses in terms of overall survival (OS), with a combined hazard ratio (HR) of 0.65 [95% confidence interval (95%CI): 0.46-0.93, P = 0.02, n = 2780]. Consistently, progression free survival (PFS) and time to progression (TTP) differed significantly between the sorafenib plus TACE arm and sorafenib arm (PFS: HR = 0.62, 95%CI: 0.40-0.96, P = 0.03, n = 443; TTP: HR = 0.73, 95%CI: 0.64-0.83, P < 0.00001, n = 2451). Disease control rate (DCR) was also significantly increased by combination therapy (risk ratio = 1.36, 95%CI: 1.02-1.81, P = 0.04, n = 641). Regarding safety, the incidence of any adverse event (AE) was increased due to the addition of TACE; however, no significant difference was found in grade ≥ 3 AEs.
CONCLUSIONS: The combination of sorafenib with TACE has superior efficacy to sorafenib monotherapy, as evidenced by prolonged OS, PFS, and TTP, as well as increased DCR. Additional high-quality trials are essential to further validate the clinical benefit of this combination in the treatment of advanced HCC.