Low-Dose Versus Standard-Dose Bevacizumab Plus Sintilimab for Unresectable Hepatocellular Carcinoma: A Real-World Comparative Study of Efficacy and Safety

Background/Aim: Sintilimab combined with bevacizumab (Sinti-Bev) is recommended as first-line treatment for unresectable hepatocellular carcinoma (uHCC) in China. However, the IMbrave150 and ORIENT-32 trials reported treatment-related adverse events (TRAEs) leading to bevacizumab interruption or discontinuation. Therefore, we aimed to explore the clinical impact of low-dose bevacizumab combined with sintilimab as a first-line therapy in patients with uHCC. Patients and Methods: A total of 85 patients who received Sinti-Bev as first-line therapy were retrospectively analyzed. Patients were stratified into low-dose (7.5 mg/kg, n=47) and high-dose (15 mg/kg, n=38) groups according to bevacizumab dosage. Antitumor efficacy, TRAEs incidence, and treatment duration were compared between groups. Inverse probability of treatment weighting (IPTW) was applied to balance baseline covariates. Results: In our study, although 91.8% of patients received Sinti-Bev combined with transarterial therapy (TAT), there was no significant difference in the number of TAT between groups. The low-dose group did not show significantly shorter progression-free survival (PFS: 9.4 vs.10.5 months, P = 0.837) and objective response rate (ORR: 61.70% vs. 63.16%, P = 0.890) compared with the high-dose group. Nevertheless, the overall survival (OS) rates in the low-dose group were numerically higher than those in the high-dose group (6/12/18 months: 94%/77%/55% vs. 91%/71%/48%). Post-IPTW analyses yielded consistent findings. Importantly, the incidence of esophagogastric variceal (EGV) bleeding was numerically lower in the low-dose group (10.6% vs. 21.1%), with fewer grade ≥3 bleeding events (6.38% vs. 18.42%). After IPTW adjustment, the median treatment duration was approximately 2.5 months longer in the low-dose group (12.0 vs. 9.5 months). Conclusion: Compared to high-dose bevacizumab combined with sintilimab, the low-dose regimen showed no significant differences in PFS, OS, or ORR, while improving safety and treatment continuity. Low-dose bevacizumab may serve as a safer alternative dose for uHCC patients with increased bleeding risk.