Advanced Management Strategies in Hepatocellular Carcinoma

In a retrospective cohort of patients with advanced hepatocellular carcinoma, FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) combined with a PD-(L)1 inhibitor and bevacizumab demonstrated superior tumor control and longer progression-free survival compared with HAIC combined with a PD-(L)1 inhibitor and tyrosine kinase inhibitors (TKIs).

The cohort-level comparison reports meaningful differences in primary efficacy endpoints while retaining the limitations inherent to nonrandomized analyses, and should therefore be interpreted as hypothesis-generating, supporting further prospective evaluation of HAIC-based triplet strategies in advanced HCC.

Median progression-free survival in the bevacizumab-containing triplet cohort was 10.9 months versus 7.4 months in the TKI-based triplet cohort, and objective response rates were 83.9% versus 61.8%, respectively, based on RECIST 1.1 criteria—findings that favor greater tumor shrinkage and delayed progression with bevacizumab as the anti-angiogenic component. Both regimens incorporated HAIC and PD-(L)1 inhibition, and the observed differences therefore reflect variation in the anti-angiogenic agent rather than immunotherapy exposure alone.

Adverse-event patterns differed by regimen. Bevacizumab-containing therapy was associated with substantially higher bleeding: gastrointestinal hemorrhage occurred in 45.2% of patients in the bevacizumab cohort versus 8.8% in the TKI cohort, and gastric ulceration was markedly more frequent with bevacizumab. Importantly, most hemorrhagic events in the bevacizumab group were grade 1–2 and were frequently detected through routine fecal occult blood testing rather than clinically overt bleeding, although the absolute incidence remained meaningfully higher. Hepatic enzyme elevations and cutaneous toxicities were relatively more common in the TKI group. Improved tumor control with the bevacizumab-based triplet therefore requires careful balancing against increased hemorrhagic risk, particularly in patients with portal hypertension.

Key Takeaways:

• HAIC combined with PD-(L)1 inhibition and bevacizumab was associated with higher objective response rates and longer median PFS than HAIC combined with PD-(L)1 inhibition and TKIs in this retrospective cohort.
• Treatment-related bleeding risk—predominantly low grade but frequent—increased with bevacizumab-containing regimens; baseline endoscopic risk assessment and proactive mitigation strategies are recommended prior to initiation.