Comparing PD-L1 and PD-1 inhibitors plus bevacizumab combined with hepatic arterial interventional therapies in unresetable hepatocellular carcinoma: A single-center, real-world study

With the rise of anti-vascular endothelial growth factor antibody and programmed cell death-ligand 1 (PD-L1) regimens, particularly bevacizumab and atezolizumab, as first-line treatments for advanced hepatocellular carcinoma (HCC), there is a need to explore PD-L1 and programmed cell death 1 inhibitors in combination therapies for unresectable HCC (uHCC). Integrating systemic therapies with locoregional approaches is also emerging as a potent strategy. This study compares the outcomes of atezolizumab (PD-L1 inhibitor) and sintilimab (programmed cell death 1 inhibitor) with bevacizumab or its biosimilar, combined with hepatic arterial interventional therapies (HAIT) in uHCC patients. From January 2020 to September 2023, a retrospective analysis was conducted on 138 uHCC patients at Sun Yat-sen University Cancer Center. The cohort included 69 patients treated with atezolizumab with bevacizumab (Bev/Ate) and 69 with bevacizumab biosimilar with sintilimab (Bio/Sin), combined with HAIT. The propensity score matching was also employed to further explore the efficacy and safety. The median progression-free survival (mPFS) was 13.8 months for the Bev/Ate group and 10.0 months for the Bio/Sin group (p = 0.188). The Bev/Ate group showed significantly longer intrahepatic mPFS (HR 0.381; 95% confidence interval 0.176–0.824; p = .018) and higher overall response rates compared with the Bio/Sin group (60.87% vs. 31.88%, p = .001; 69.57% vs. 49.28%, p = .024) based on Response Evaluation Criteria in Solid Tumors v1.1 and modified Response Evaluation Criteria in Solid Tumors criteria. Treatment-related adverse events were similar between groups (p > .050). Combining atezolizumab or sintilimab with bevacizumab or its biosimilar alongside HAIT provided similar overall PFS in uHCC patients. However, the atezolizumab-bevacizumab combination with HAIT showed superior intrahepatic PFS and control rates, warranting further validation.