Hepatic arterial infusion chemotherapy plus lenvatinib and programmed death receptor 1 inhibitor for hepatocellular carcinoma with portal vein tumor thrombosis: a prospective controlled study

Lenvatinib plus programmed death receptor 1 (PD-1) inhibitor had shown efficacy for hepatocellular carcinoma (HCC) with macrovascular invasion, and hepatic arterial infusion chemotherapy (HAIC) had shown promising efficacy for HCC with portal vein tumor thrombosis (PVTT). This trial was to compare the efficacy and safety of HAIC combined with Lenvatinib and PD-1 inhibitor to Lenvatinib plus PD-1 inhibitor for advanced HCC with PVTT. In this open-label, single-center, prospective controlled study, participants with treatment-naïve advanced HCC and PVTT were enrolled from December 2021 to December 2023 and assigned to receive either HAIC combined with Lenvatinib and PD-1 inhibitor (Lenva-PD1-HAIC group) or Lenvatinib plus PD-1 inhibitor (Lenva-PD1 group). The primary endpoint was six-month progression-free survival (PFS) rate. Overall survival (OS), PFS, objective response rate (ORR) per mRECIST criteria, time to progression (TTP), and safety were also investigated. A total of 66 participants were enrolled, with 33 in each group. The 6-month PFS rate was 78.8% vs. 46.9% (cloglog P = 0.013). Median PFS (13.7 vs. 5.9 months, hazard ratio [HR]: 0.422, 95% confidence interval [CI]: 0.229 – 0.778, log-rank P = 0.004), OS (25.4 vs. 12.6 months, HR: 0.502, 95% CI: 0.273 – 0.926, log-rank P = 0.024), and TTP (15.1 vs. 6.2 months, HR: 0.345, 95% CI: 0.170 – 0.700, log-rank P = 0.002) were longer than those in the Lenva-PD1 group, with the ORR per mRECIST criteria of 78.8% vs. 42.4% ( P = 0.003). Sensitivity analysis using propensity score overlap weighting yielded treatment effect estimates that were generally similar in both direction and magnitude with the primary findings. The incidence of Grade 3 – 4 treatment-related adverse events in the Lenva-PD1-HAIC and Lenva-PD1 groups was 57.6% vs. 42.4%. HAIC combined with Lenvatinib and PD-1 inhibitor was associated with improved efficacy and acceptable safety profile for advanced HCC with PVTT compared to Lenvatinib plus PD-1 inhibitor. Sensitivity analyses yielded generally similar treatment effect estimates, and confirmation in larger randomized studies is warranted. This trial was registered at ClinicalTrials.gov (NCT05166239).