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 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, progression-free survival, objective response rate, and safety were compared between the two groups. Propensity score matching was performed to reduce bias between the two groups. Results: After propensity score matching (1:1), 194 patients in each group were analyzed. The triple-therapy group showed a longer median overall survival (24.6 vs. 11.9 months; HR=0.43, P <0.001) and a longer median progression-free survival (10.0 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 objective response rate 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 hepatic arterial infusion chemotherapy 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.