Hepatic arterial chemotherapy infusion combined with tyrosine kinase inhibitors and PD-1 inhibitors for advanced hepatocellular carcinoma with high-risk: A propensity score matching study

Objective: 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). Methods: 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. Results: 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). Conclusion: 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.