确定基于 FOLFOX（奥沙利铂、氟尿嘧啶和亚叶酸）的肝动脉灌注化疗（HAIC）联合酪氨酸激酶抑制剂（TKI）和程序性细胞死亡蛋白-1 抑制剂（PD-1 抑制剂）的治疗效果和安全性（三联疗法）疗法），作为高危晚期肝细胞癌（伴有 Vp4 门静脉侵犯或/和肿瘤直径 ≥ 10 cm 的 aHCC）的一线治疗。这项回顾性多中心研究包括 466 名接受三联疗法（ n = 245）或双重治疗（TKI 和 PD-1 抑制剂，n = 221）。比较两组的总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和安全性。进行倾向评分匹配（PSM）以减少两组之间的偏差。PSM（1：1）后，对每组194名患者进行分析。与双联疗法相比，三联疗法组的中位 OS 更长（24.6 个月 vs. 11.9 个月；HR = 0.43，P < 0.001），中位 PFS 更长（10.0 个月 vs. 7.7 个月；HR = 0.68，P = 0.002）。 -治疗组。三联疗法6、12和24个月的生存率分别为94.2%、71.0%和50.8%，双联疗法分别为75.9%、49.9%和26.8%。三联疗法组的 ORR 显着较高（57.7% vs. 28.9%，P < 0.001）。在三联治疗组中，更多患者转为非高危患者（68.0% vs. 36.6%，P < 0.001）并在降期转化后接受挽救性肝切除或消融（16.5% vs. 9.2%，P = 0.033） 。三联疗法组和双联疗法组的3/4级不良事件发生率分别为59.2%和47.4%（P=0.022）。基于FOLFOX的HAIC联合TKI和PD-1抑制剂与TKI相比显着改善生存预后加 PD-1 抑制剂。这是高风险 aHCC 的潜在一线治疗方法，具有相对可控的安全性。版权所有 © 2024 作者。由 Wolters Kluwer Health, Inc. 出版

To ascertain the therapeutic efficacy and safety of FOLFOX (oxaliplatin, fluorouracil, and leucovorin)-based hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKI) and programmed cell death protein-1 inhibitors (PD-1 inhibitors) (triple therapy), as a first-line treatment in high-risk advanced hepatocellular carcinoma (aHCC with Vp4 portal vein invasion or/and tumor diameter ≥ 10 cm).This retrospective multicenter study included 466 high-risk aHCC patients treated with either triple therapy (n = 245) or dual therapy (TKI and PD-1 inhibitors, n = 221). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were compared between the two groups. Propensity score matching (PSM) was performed to reduce bias between the two groups.After PSM (1:1), 194 patients in each group were analyzed. The triple-therapy group showed a longer median OS (24.6 months vs. 11.9 months; HR = 0.43, P < 0.001) and a longer median PFS (10.0 months vs. 7.7 months; HR = 0.68, P = 0.002) than the dual-therapy group. The survival rates at 6, 12, and 24 months were 94.2%, 71.0%, and 50.8% for triple therapy and 75.9%, 49.9%, and 26.8% for dual therapy. The ORR in the triple-therapy group was significantly higher (57.7% vs. 28.9%, P < 0.001). In the triple-therapy group, more patients converted to non-high-risk (68.0% vs. 36.6%, P < 0.001) and received salvage liver resection or ablation after downstaging conversion (16.5% vs. 9.2%, P = 0.033). The grade 3/4 adverse events were 59.2% and 47.4% in the triple-therapy group and dual-therapy group, respectively (P = 0.022).FOLFOX-based HAIC plus TKI and PD-1 inhibitors significantly improve survival prognosis compared with TKI plus PD-1 inhibitors. This is a potential first-line treatment for high-risk aHCC, with a relatively controlled safety profile.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.