Abstract
INTRODUCTION: The combination of anti-angiogenic agents, PD-1/L1 inhibitors, and hepatic arterial infusion chemotherapy (HAIC) has emerged as an important strategy for unresectable hepatocellular carcinoma (uHCC), yet comparative data on efficacy and safety between different anti-angiogenic agents (lenvatinib [LenHAP] or bevacizumab [BevHAP]) remain lacking, especially in patients with potential resectable features (PotenR). METHODS: This retrospective study included patients from 3 hospitals. Included patients received LenHAP or BevHAP as the first-line treatment. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), conversion resection rate (CRR) and adverse events (AE) were compared. RESULTS: We included 108 uHCC patients in each group after propensity score matching (PSM), of which PotenR patients accounted for 34.3%. Compared with BevHAP group, the LenHAP group demonstrated significantly prolonged median PFS (12.6 vs. 8.1 months; HR, 0.64; 95% CI, 0.46-0.90; p=0.0085), with a trend toward improved OS (26.4 vs. 19.6 months; HR, 0.71; 95% CI, 0.41-1.1; p=0.091). PotenR patients receiving LenHAP achieved superior outcomes, including markedly extended OS (both not reached in median, p=0.018), PFS (19.8 vs. 11.5, months, p=0.0067), and higher conversion resection rates (52.6% vs. 25.0%, p=0.015). Both regimens showed comparable safety profiles, with similar frequencies of grade 3-4 adverse events (47.2% vs. 39.8%, p=0.27) and serious adverse events (4.6% vs. 8.3%, p=0.27). CONCLUSIONS: LenHAP might offer enhanced clinical benefits over BevHAP in uHCC, particularly for PotenR patients, while maintaining equivalent tolerability.