HAIC combined with lenvatinib and PD-1 inhibitors versus lenvatinib plus PD-1 inhibitors for advanced HCC with portal vein tumor thrombosis: A prospective controlled trial

BackgroundThe LEAP-002 trial showed Lenvatinib plus Pembrolizumab (a programmed death-1 [PD-1] inhibitor) was more beneficial to patients with hepatocellular carcinoma (HCC) and macrovascular invasion compared to Lenvatinib alone. Recently, hepatic arterial infusion chemotherapy (HAIC) has shown promising results for advanced HCC with portal vein tumor thrombosis (PVTT). This trial was to compare the efficacy and safety of HAIC combined with Lenvatinib and PD-1 inhibitors to Lenvatinib plus PD-1 inhibitors for patients with advanced HCC and PVTT.MethodsParticipants with advanced HCC and PVTT were enrolled and assigned 1:1 to HAIC + Lenvatinib + PD-1 inhibitor group (Lenva-PD1-HAIC group) or Lenvatinib + PD-1 inhibitor group (Lenva-PD1 group). HAIC was performed via a percutaneously implanted port-catheter system with 3cir-OFF regimen (oxaliplatin [35 mg/m2, 0-2h, d1-3] and 5-fluorouracil [600 mg/m2, 2-24h, d1-3], repeated every 4 weeks). Lenvatinib was administered orally (12 mg/d [≥ 60 kg] or 8 mg/d [< 60 kg]), and PD-1 inhibitors were administered intravenously on day 1 every 3-4 weeks. Six-month progression-free survival (PFS) rate, overall survival (OS), PFS, objective response rate (ORR) (mRECIST criteria), time to progression (TTP), and safety were compared.ResultsFrom December 2021 to December 2023, 66 participants were enrolled with 33 in each group. The 6-month PFS rate was 78.8% vs. 46% (p = 0.011). The median PFS was 12.3 vs. 5.9 months (p = 0.001), and the median TTP was 12.3 vs. 5.3 months (p = 0.002). The median OS was not reached vs. 15.7 months, with the 1- and 2-year OS rate of 73.8% vs. 60% and 61.6% vs. 30.5%, respectively. The ORR was 75.8% vs. 37.5% (mRECIST criteria) (p = 0.006). The incidence of Grade 3-4 treatment-related adverse events (AEs) was 51.5% vs. 30.3%. Elevated AST (6/33, 18.2%)was the most frequent Grade 3-4 AEs in Lenva-PD1-HAIC group, while hypertension (6/33, 18.2%) was the most frequent Grade 3-4 AEs in Lenva-PD1 group.ConclusionsHAIC combined with Lenvatinib and PD-1 inhibitors showed greater efficacy and acceptable safety profile for advanced HCC with PVTT compared to Lenvatinib plus PD-1 inhibitors.Clinical trial identificationNCT05166239; Release date: 11/26/2021.Legal entity responsible for the studyThe authors.FundingNational Natural Science Foundation of China (No. 82172039), Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (No. ZYLX202117), and Beijing Natural Science Foundation (No. 7212198).DisclosureAll authors have declared no conflicts of interest.