Department of Liver Surgery, Sun Yat-sen University Cancer Center.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine.
Int J Surg. 2024 Jul 1;110(7):4062-4073. doi: 10.1097/JS9.0000000000001378.
Lenvatinib plus programmed death-1 (PD-1) inhibitors (LEN-P) have been recommended in China for patients with advanced hepatocellular carcinoma (HCC). However, they provide limited survival benefits to patients with extrahepatic metastases. We aimed to investigate whether combining hepatic arterial infusion chemotherapy (HAIC) with LEN-P could improve its efficacy.
This multicenter cohort study included patients with HCC extrahepatic metastases who received HAIC combined with LEN-P (HAIC-LEN-P group, n =127) or LEN-P alone ( n =103) as the primary systemic treatment between January 2019 and December 2022. Baseline data were balanced using a one-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).
After PSM, the HAIC-LEN-P group significantly extended the median overall survival (mOS) and median progression-free survival (mPFS), compared with the LEN-P group (mOS: 27.0 months vs. 9.0 months, P <0.001; mPFS: 8.0 months vs. 3.0 months, P =0.001). After IPTW, the mOS [hazard ratio (HR)=0.384, P <0.001] and mPFS (HR=0.507, P <0.001) were significantly higher in the HAIC-LEN-P group than in the LEN-P group. The HAIC-LEN-P group's objective response rate was twice as high as that of the LEN-P group (PSM cohort: 67.3% vs. 29.1%, P <0.001; IPTW cohort: 66.1% vs. 27.8%, P <0.001). Moreover, the HAIC-LEN-P group exhibited no noticeable increase in the percentages of grade 3 and 4 adverse events compared with the LEN-P group ( P >0.05).
HAIC can improve the efficacy of LEN-P in patients with HCC extrahepatic metastases and may be an alternative treatment for advanced HCC management.
仑伐替尼联合程序性死亡受体-1（PD-1）抑制剂（LEN-P）已被推荐用于中国晚期肝细胞癌（HCC）患者。然而，它们为肝外转移的患者提供的生存获益有限。我们旨在研究联合肝动脉灌注化疗（HAIC）与 LEN-P 是否可以提高其疗效。
这项多中心队列研究纳入了 2019 年 1 月至 2022 年 12 月期间接受 HAIC 联合 LEN-P（HAIC-LEN-P 组，n=127）或 LEN-P 单药（n=103）作为一线全身治疗的 HCC 肝外转移患者。使用 1:1 倾向评分匹配（PSM）和逆概率治疗加权（IPTW）来平衡基线数据。
PSM 后，HAIC-LEN-P 组的中位总生存期（mOS）和中位无进展生存期（mPFS）均显著长于 LEN-P 组（mOS：27.0 个月 vs. 9.0 个月，P<0.001；mPFS：8.0 个月 vs. 3.0 个月，P=0.001）。IPTW 后，HAIC-LEN-P 组的 mOS（风险比[HR]=0.384，P<0.001）和 mPFS（HR=0.507，P<0.001）显著高于 LEN-P 组。HAIC-LEN-P 组的客观缓解率是 LEN-P 组的两倍（PSM 队列：67.3% vs. 29.1%，P<0.001；IPTW 队列：66.1% vs. 27.8%，P<0.001）。此外，HAIC-LEN-P 组与 LEN-P 组相比，3 级和 4 级不良事件的百分比没有明显增加（P>0.05）。
HAIC 可提高 LEN-P 治疗 HCC 肝外转移患者的疗效，可能是晚期 HCC 管理的一种替代治疗方法。
