Wang Wei, Li Ruixia, Li Hui, Wang Murong, Wang Juncheng, Wang Xiaohui, Zhou Qunfang
Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People's Republic of China.
Department of Thyroid Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
Immunotargets Ther. 2024 Aug 19;13:399-412. doi: 10.2147/ITT.S470797. eCollection 2024.
The prognosis of infiltrative hepatocellular carcinoma (HCC) is dismal. Hepatic arterial infusion chemotherapy (HAIC) plus Lenvatinib (Len) and immune checkpoint inhibitor (ICI) have shown promising results for HCC. However, this three combination therapy on infiltrative HCC is unknown. In this study, we compared HAIC plus lenvatinib (Len) and programmed cell death protein-1 (PD-1) inhibitor with HAIC plus Len for infiltrative HCC.
This multi-center cohort study included patients with infiltrative HCC who received HAIC combined with Len (HAIC+Len group, n = 173) or HAIC combined with Len and PD-1 inhibitor (HAIC+Len+ICI group, n = 128) as the first-line treatment from January 2019 to December 2021. To balance any intergroup differences, one-to-one propensity score matching (PSM) was applied. Overall survival (OS) and progression-free survival (PFS) were compared between the two groups.
After PSM, the median OS was 14.1 ± 1.0 and 16.1 ± 1.4 months in the HAIC+Len and HAIC+Len+ICI groups, respectively. The median PFS was 4.6 ± 0.4 months in the HAIC+Len group and 7.5 ± 0.8 months in the HAIC+Len+ICI group. The HAIC+Len+ICI group showed significantly better OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.90; = 0.008) and PFS (HR, 0.53; 95% confident index [CI], 0.40-0.70; < 0.001) compared with the HAIC+Len group. Subgroup analysis revealed that for OS in HCC without metastasis, the addition of PD-1 inhibitor was not significant (HR, 0.68; 95% CI, 0.43-1.07; = 0.091). No difference was observed in OS between low (2-3 cycles) and high (4-6 cycles) level of HAIC cycles (HR, 0.99; 95% CI, 0.67-1.44; = 0.938).
The HAIC+Len+ICI group had a longer PFS and OS compared with the HAIC+Len group, demonstrating an acceptable safety profile. This triple combination strategy may be an alternative treatment for infiltrative HCC management.
浸润性肝细胞癌（HCC）的预后较差。肝动脉灌注化疗（HAIC）联合乐伐替尼（Len）及免疫检查点抑制剂（ICI）已在HCC治疗中显示出良好疗效。然而，这种三联疗法对浸润性HCC的疗效尚不清楚。在本研究中，我们比较了HAIC联合乐伐替尼（Len）及程序性细胞死亡蛋白-1（PD-1）抑制剂与HAIC联合乐伐替尼（Len）治疗浸润性HCC的效果。
这项多中心队列研究纳入了2019年1月至2021年12月期间接受HAIC联合Len（HAIC+Len组，n = 173）或HAIC联合Len及PD-1抑制剂（HAIC+Len+ICI组，n = 128）作为一线治疗的浸润性HCC患者。为平衡组间差异，采用一对一倾向评分匹配（PSM）。比较两组的总生存期（OS）和无进展生存期（PFS）。
PSM后，HAIC+Len组和HAIC+Len+ICI组的中位OS分别为14.1±1.0个月和16.1±1.4个月。HAIC+Len组的中位PFS为4.6±0.4个月，HAIC+Len+ICI组为7.5±0.8个月。与HAIC+Len组相比，HAIC+Len+ICI组的OS（风险比[HR]，0.66；95%可信区间[CI]，0.49 - 0.90；P = 0.008）和PFS（HR，0.53；95%可信区间[CI]，0.40 - 0.70；P < 0.001）显著更好。亚组分析显示，对于无转移的HCC患者，添加PD-1抑制剂对OS无显著影响（HR，0.68；95%CI，0.43 - 1.07；P = 0.091）。HAIC周期数低（2 - 3个周期）和高（4 - 6个周期）的患者之间OS无差异（HR，0.99；95%CI，0.67 - 1.44；P = 0.938）。
与HAIC+Len组相比，HAIC+Len+ICI组的PFS和OS更长，安全性良好。这种三联组合策略可能是浸润性HCC治疗的一种替代方案。
