Nivolumab Plus Lenvatinib and Intra-Arterial Locoregional Therapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Real-World Study

Background: Although first-line triple therapy of programmed death-1 inhibitors plus lenvatinib and intra-arterial locoregional therapy has shown potential clinical benefit for unresectable hepatocellular carcinoma (HCC), it has not yet been established as a standard treatment. This real-world study evaluated the efficacy and safety of first-line combination therapy with nivolumab, lenvatinib, and intra-arterial locoregional therapy (including transarterial chemoembolization or hepatic arterial infusion chemotherapy) in this population. Methods: This retrospective study included untreated unresectable HCC patients who received nivolumab plus lenvatinib and intra-arterial locoregional therapy between 26 March 2020 and 17 October 2023. The outcomes included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 52 patients were included, the majority of whom were < 65 years (86.5%) and male (90.4%). Most patients had compensated liver disease, with 92.3% classified as Child–Pugh class A. The ORR was 69.2% (95% confidence interval [CI]: 54.9%– 81.3%) per mRECIST and 55.8% (95% CI: 41.3%– 69.5%) per RECIST version 1.1. The DCR was 100% by both criteria. The median DoR was 12.1 months per mRECIST and 10.5 months per RECIST version 1.1. With a median follow-up of 22.0 months (range: 1.6– 57.3), the median PFS was 16.8 months (95% CI: 12.9– 20.5) per mRECIST and 16.6 months (95% CI: 12.8– 20.2) per RECIST version 1.1. The median OS was 24.9 months (95% CI: 21.7– 35.6). Treatment-emergent adverse events (TEAEs) of any grade occurred in 45 patients (86.5%), with fatigue (30.8%) being the most common. Grade ≥ 3 TEAEs were observed in 17.3% of patients. Conclusion: First-line nivolumab plus lenvatinib and intra-arterial locoregional therapy showed encouraging antitumor activity and a manageable safety profile in unresectable HCC.