What question did this study set out to answer?

This study aims to compare the efficacy and safety of two therapeutic strategies for advanced hepatocellular carcinoma (HCC) involving HAIC and either bevacizumab or TKIs.

January 22, 2026Open Access

Efficacy and Safety of HAIC Combined with PD-(L)1 Inhibitors and Bevacizumab Versus HAIC with PD-(L)1 Inhibitors and TKIs in Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study

Key Points

This study aims to compare the efficacy and safety of two therapeutic strategies for advanced hepatocellular carcinoma (HCC) involving HAIC and either bevacizumab or TKIs.
Retrospective cohort analysis of 65 patients with advanced HCC.
Patients received HAIC combined with immune checkpoint inhibitors and either bevacizumab (31 patients) or TKIs (34 patients).
Primary endpoints assessed included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and adverse events.
Bevacizumab group demonstrated significantly longer median PFS (10.9 vs. 7.4 months) and higher ORR (83.9% vs. 61.8%).
DOR was longer in the bevacizumab group (7.9 vs. 5.3 months).
Median overall survival was not reached in the bevacizumab group, while the TKIs group had 22.6 months.
67.7% of patients in the bevacizumab group experienced grade 3–4 adverse events, compared to 73.5% in the TKIs group, with different adverse event profiles.

Abstract

Background: The combination of hepatic arterial infusion chemotherapy (HAIC) with immune checkpoint inhibitors (ICIs) and anti-angiogenic agents represents a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC). This study aimed to compare the efficacy and safety of triple therapies combining HAIC with ICIs and either bevacizumab or tyrosine kinase inhibitors (TKIs) in these patients. Methods: This retrospective single-center study enrolled 65 consecutive patients with advanced HCC who received HAIC combined with ICIs plus either bevacizumab (bevacizumab group, n = 31) or TKIs (TKIs group, n = 34) between June 2021 and June 2023. Primary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety profiles. Results: The bevacizumab group demonstrated significantly prolonged median PFS (10.9 vs. 7.4 months, p = 0.001) and higher ORR (83.9% vs. 61.8%, p = 0.047) compared with the TKIs group. DOR was longer in the bevacizumab group (7.9 vs. 5.3 months, p = 0.008). Median overall survival (OS) was not reached in the bevacizumab group versus 22.6 months in the TKIs group. Grade 3–4 adverse events occurred in 67.7% of the bevacizumab group and 73.5% of the TKIs group, with distinct toxicity profiles. Gastrointestinal hemorrhage (45.2%) and gastric ulcer (22.6%) predominated in the bevacizumab group, whereas the TKIs group exhibited more hepatic enzyme elevations (aspartate aminotransferase, 67.6%; alanine aminotransferase, 61.8%), proteinuria (29.4%), diarrhea (26.5%), hand-foot syndrome (20.6%), and reactive cutaneous capillary endothelial proliferation (11.8%). Conclusions: Bevacizumab-containing triplet therapy was associated with improved tumor control and delayed progression compared to TKIs-based regimens in advanced HCC. The higher bleeding risk in the bevacizumab group highlights the necessity of standardized baseline evaluation and adequate preventive measures.

Efficacy and Safety of HAIC Combined with PD-(L)1 Inhibitors and Bevacizumab Versus HAIC with PD-(L)1 Inhibitors and TKIs in Advanced Hepatocellular Carcinoma: A Retrospective Cohort Study

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