背景:全身转换治疗为最初无法切除的肝细胞癌(HCC)患者提供了挽救根治性肝切除术和优越生存结果的机会,但最优转换策略尚不清楚。
方法:在PubMed上进行了系统的文献检索,EMBASE,WebofScience,Scopus,2007年至2024年期间,Cochrane图书馆专注于报告HCC转化治疗的研究。治疗组分为酪氨酸激酶抑制剂(TKI),TKI加局部治疗(LRT),TKI加抗PD-1治疗(TKI+PD-1),TKI+PD-1+轻轨,免疫检查点抑制剂(ICI)加LRT,阿替珠单抗加贝伐单抗(A+T)组。转换为手术率(CSR),客观反应率(ORR),≥3级治疗相关不良事件(AE),分析总生存期(OS)和无进展生存期(PFS).
结果:纳入了38项研究和4,042例患者。TKI组合并的CSR为8%(95%CI,5-12%),TKI+LRT组13%(95%CI,8-19%),TKI+PD-1组28%(95%CI,19-37%),TKI+PD-1+LRT组33%(95%CI,25-41%),ICI+LRT组23%(95%CI,1-46%),A+T组为5%(95%CI,3-8%),分别。OS(0.45,95%CI,0.35-0.60)和PFS(0.49,95%CI,0.35-0.70)的合并HR有利于转换手术的生存益处。亚组分析显示,乐伐替尼+PD-1+LRT赋予了更高的企业社会责任35%(95%CI,26-44%),ORR增加了70%(95%CI,56-83%)。
结论:目前的研究表明,TKI+PD-1+LRT,尤其是lenvatinib+PD-1+LRT,对于最初无法切除的HCC患者,可能是具有可管理的安全性的优良转化疗法。与单独的全身治疗相比,成功的转化治疗有利于优越的OS和PFS。
背景:国际前瞻性系统评价注册(PROSPERO)(注册码:CRD42024495289)。
BACKGROUND: Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear.
METHODS: A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed.
RESULTS: 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35-0.60) and PFS (0.49, 95% CI, 0.35-0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%).
CONCLUSIONS: The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone.
BACKGROUND: International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).