# 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

## TL;DR

A study found that combining HAIC with PD-(L)1 inhibitors and bevacizumab improved outcomes in advanced liver cancer compared to using tyrosine kinase inhibitors.

## Contribution

This study provides real-world evidence comparing two triplet therapies for advanced hepatocellular carcinoma in a clinical setting.

## Key findings

- Bevacizumab-based regimen showed higher objective response rate (83.9%) compared to TKI-based regimen (61.8%).
- Median progression-free survival was longer with bevacizumab (10.9 months) than with TKIs (7.4 months).
- Both regimens had manageable toxicity but with distinct adverse event profiles.

## Abstract

This retrospective study compared the efficacy and safety of two triplet regimens—hepatic arterial infusion chemotherapy (HAIC) plus immune checkpoint inhibitors combined with either bevacizumab or tyrosine kinase inhibitors (TKIs)—in patients with advanced hepatocellular carcinoma (HCC). Among 65 enrolled patients, the bevacizumab-based regimen suggested improved tumor control, with a higher objective response rate (83.9% vs. 61.8%) and longer median progression-free survival (10.9 vs. 7.4 months) compared to the TKI-based regimen. Both regimens exhibited manageable toxicity profiles, but with distinct adverse event profiles. These real-world findings suggest that the triple combination containing bevacizumab may offer a more effective treatment option, warranting further validation in prospective clinical trials.

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.