Comparative efficacy and safety of donafenib versus bevacizumab in combination with immune checkpoint inhibitors and interventional therapy for advanced hepatocellular carcinoma: A retrospective cohort study.

Abstract

e16305 Background: Advanced hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with a particularly high burden in China due to chronic hepatitis B virus (HBV) infection. While combination therapies such as atezolizumab plus bevacizumab have established new standards in first-line treatment, their efficacy remains suboptimal in certain populations. This study compares the efficacy and safety of donafenib versus bevacizumab, both combined with immune checkpoint inhibitors (ICIs) and interventional therapies, to identify optimal strategies for Chinese patients with unresectable HCC. Methods: This retrospective cohort study included 150 Chinese patients with unresectable HCC treated at Tianjin Medical University Cancer Institute and Hospital between November 2017 and December 2023. Patients were assigned to two groups: 109 in the bevacizumab-based regimen and 41 in the donafenib-based regimen, both receiving triple therapy with immune checkpoint inhibitors (ICIs) and interventional treatments (TACE or HAIC). After propensity score matching (PSM), 60 patients remained in the bevacizumab group and 34 in the donafenib group. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders. Primary outcomes included overall survival (OS) and progression-free survival (PFS), while secondary outcomes included objective response rate (ORR) and disease control rate (DCR), assessed per the mRECIST criteria, along with treatment-related adverse events (TRAEs). Results: In the matched cohort, median overall survival (OS) was 28.0 months (95% CI, 17.5–28.0), with no significant difference between groups (HR, 0.901; P = 0.829). Median progression-free survival (PFS) was 11.1 months (95% CI, 8.0–13.6), with no significant difference between groups (HR, 1.021; P = 0.954). The donafenib group had an objective response rate (ORR) of 59.3% and disease control rate (DCR) of 92.6%, while the bevacizumab group had ORR of 52.0% and DCR of 98.0%. Adverse events occurred in 100% of donafenib patients and 91.5% of bevacizumab patients (P = 0.16). Serious (Grade ≥3) treatment-related adverse events occurred in 28.6% of donafenib patients and 38.3% of bevacizumab patients (P = 0.50). No treatment-related deaths were reported. Conclusions: Donafenib-based triple therapy demonstrated comparable efficacy and safety to bevacizumab-based regimens in advanced HCC, offering a potential cost-effective alternative for Chinese patients. These findings underscore the importance of personalized treatment strategies in regions with a high incidence of HCC.