背景:由于缺乏直接的比较研究和标准的治疗方案,在一线治疗失败后选择合适的二线治疗肝癌的临床挑战很大。网络荟萃分析(NMA)提供了一种强大的方法来系统地评估肝细胞癌(HCC)的各种二线治疗的临床结果和不良反应。
方法:我们系统地搜索了PubMed,Embase,WebofScience和Cochrane图书馆确定截至2024年3月11日发表的III/IV期随机对照试验(RCT)。提取的结果是中位总生存期(OS),中位无进展生存期(PFS),疾病进展时间(TTP),疾病控制率(DCR),客观反应率(ORR),和不良反应。本研究已在前瞻性系统审查登记册(CRD42023427843)中注册,以确保透明度。新奇,和可靠性。
结果:我们纳入了16个RCTs,涉及7,005例患者和10个二线治疗。对于晚期肝癌患者,与安慰剂相比,瑞戈非尼(HR=0.62,95CI:0.53-0.73)和卡博替尼(HR=0.74,95CI:0.63-0.85)的OS获益最好.卡博替尼(HR=0.42,95CI:0.32-0.55)和瑞戈非尼(HR=0.46,95%CI:0.31-0.68)也提供了最显著的PFS益处。对于TTP,阿帕替尼(HR=0.43,95%CI:0.33-0.57),雷莫珠单抗(HR=0.44,95%CI:0.34-0.57),与安慰剂相比,瑞戈非尼(HR=0.44,95%CI:0.38-0.51)显示出显著的获益.关于ORR,ramucirumab(OR=9.90,95%CI:3.40~42.98)和S-1(OR=8.68,95%CI:1.4~154.68)比安慰剂组增加最显著.与安慰剂相比,阿帕替尼(OR=3.88,95%CI:2.48-6.10)和卡博替尼(OR=3.53,95%CI:2.54-4.90)提供了最佳的DCR益处。Tivantinib在三种不同的安全性结果测量方面显示出最显著的优势。
结论:我们的研究结果表明,就整体疗效和安全性而言,regorafenib和cabozantinib是晚期HCC患者的最佳二线治疗选择.
BACKGROUND: The selection of appropriate second-line therapy for liver cancer after first-line treatment failure poses a significant clinical challenge due to the lack of direct comparative studies and standard treatment protocols. A network meta-analysis (NMA) provides a robust method to systematically evaluate the clinical outcomes and adverse effects of various second-line treatments for hepatocellular carcinoma (HCC).
METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library to identify phase III/IV randomized controlled trials (RCTs) published up to March 11, 2024. The outcomes extracted were median overall survival (OS), median progression-free survival (PFS), time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse reactions. This study was registered in the Prospective Register of Systematic Reviews (CRD42023427843) to ensure transparency, novelty, and reliability.
RESULTS: We included 16 RCTs involving 7,005 patients and 10 second-line treatments. For advanced HCC patients, regorafenib (HR = 0.62, 95%CI: 0.53-0.73) and cabozantinib (HR = 0.74, 95%CI: 0.63-0.85) provided the best OS benefits compared to placebo. Cabozantinib (HR = 0.42, 95%CI: 0.32-0.55) and regorafenib (HR = 0.46, 95% CI: 0.31-0.68) also offered the most significant PFS benefits. For TTP, apatinib (HR = 0.43, 95% CI: 0.33-0.57), ramucirumab (HR = 0.44, 95% CI: 0.34-0.57), and regorafenib (HR = 0.44, 95% CI: 0.38-0.51) showed significant benefits over placebo. Regarding ORR, ramucirumab (OR = 9.90, 95% CI: 3.40-42.98) and S-1 (OR = 8.68, 95% CI: 1.4-154.68) showed the most significant increases over placebo. Apatinib (OR = 3.88, 95% CI: 2.48-6.10) and cabozantinib (OR = 3.53, 95% CI: 2.54-4.90) provided the best DCR benefits compared to placebo. Tivantinib showed the most significant advantages in terms of three different safety outcome measures.
CONCLUSIONS: Our findings suggest that, in terms of overall efficacy and safety, regorafenib and cabozantinib are the optimal second-line treatment options for patients with advanced HCC.