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

Lin Xu,1, Xiao Wang,1, Xiaohuan Lai,2 An Li,3 Ye Mao,1 Xu Wang,4 Jianbing Wu1 1Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Interventional Hepatology, The Fifth People’s Hospital of Ganzhou, Ganzhou, Jiangxi, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, People’s Republic of China; 4Department of Pathology, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Jianbing Wu, Department of Oncology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi, People’s Republic of China, Email hhgwjb@163.comBackground/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.Keywords: bevacizumab, bleeding, hepatocellular carcinoma, low-dose, sintilimab