Immune Checkpoint Inhibitors Affect Post-Progression Survival of Specific Patient Subgroups With Advanced Hepatocellular Carcinoma: A Study Cohorts’ Analysis

Abstract

Objectives: Immunotherapy-based regimens (IMBs), compared with tyrosine-kinase inhibitors (TKIs), improve the overall survival (OS) of patients with advanced hepatocellular carcinoma (aHCC). The aim of the study was to explore the interaction of prognostic factors with survival in study cohorts receiving IMB or TKI.

Methods: A systematic search was performed and single arms of phase III trials including IMB or TKI were selected. Analysis of IMB and TKI cohorts was performed, and the relationship between progression-free survival (PFS) with OS was assessed. Finally, 13 variables were extracted, and their relationships with survival in the two groups were evaluated.

Results: Thirty-three study cohorts were selected. Longer OS and post-progression survival (PPS) were evident in the group of IMB, while the relationship of PFS with OS was significant only in the TKI cohorts (β = 0.527,p = 0.007). Prognostic factors in the IMB cohorts did not report any significant relationship with OS, while among patients receiving TKIs, longer OS was documented with elder age (β = 0.577,p = 0.003) and good performance status (β = 0.500,p = 0.011). Conversely, in the IMB cohorts, PPS increased with hepatitis B virus (HBV) (β = 0.756,p = 0.030) and Barcelona Clinic Liver Classification (BCLC) stage (β = 0.898,p = 0.002).

Conclusion: In contrast to TKIs, IMBs improved the outcome of patients with aHCC by increasing PPS, particularly in patients with BCLC stage C and HBV-related hepatopathy, but the outcome improvement was lost in patients with hepatitis C virus-related liver disease.

Keywords

hepatitis B / hepatocellular carcinoma / immune checkpoint inhibitors / progression-free survival / tyrosine kinase inhibitors

RIGHTS & PERMISSIONS

2025 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.