Background & Aims: The optimal treatment strategy for unresectable hepatocellular carcinoma (uHCC) remains under active investigation. Hepatic arterial infusion chemotherapy (HAIC) has shown promising outcomes, particularly among patients with high intrahepatic tumor burden. We assessed outcomes and tolerability of HAIC combined with lenvatinib and pembrolizumab (HAIC+L+P) as initial treatment for uHCC. Methods: We retrospectively identified consecutive, treatment-naïve patients with uHCC (BCLC stage B/C) treated with HAIC+L+P at a single center from January 2019 to January 2024. Tumor responses were evaluated using RECIST 1.1 and mRECIST. Overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs) were analyzed. Results: Sixty-six patients were analyzed, of whom 81.8% had BCLC stage C disease, 68.2% had vascular invasion, and 45.5% had extrahepatic metastasis. The median PFS was 9.63 months (95% CI, 6.59– 12.68), and the median OS was 27.50 months (95% CI, 18.17– 36.83). The ORR was 47.0% according to RECIST 1.1 and 66.7% according to mRECIST, with a DCR of 90.9% by both criteria. Six patients (9.1%) underwent curative-intent surgical resection during treatment. All AEs were controllable and no treatment-related deaths were recorded. Conclusion: HAIC combined with lenvatinib and pembrolizumab was associated with encouraging antitumor activity and a manageable safety profile in this real-world cohort. These findings should be considered hypothesis-generating and warrant validation in prospective controlled studies. Keywords: hepatocellular carcinoma, hepatic arterial infusion chemotherapy, lenvatinib, pembrolizumab
Liang et al. (2026) studied this question.