Rechallenge with Immune Checkpoint Inhibitors in Patients with Hepatocellular Carcinoma: A Narrative Review

Area of Science:

• Hepatocellular Carcinoma Research
• Immunotherapy
• Cancer Treatment

Background:

• Immune checkpoint inhibitors (ICIs) are used for hepatocellular carcinoma (HCC).
• Rechallenge with ICIs is a developing strategy for HCC patients who stop initial immunotherapy.
• Standardized rechallenge protocols and mechanistic understanding are lacking.

Purpose of the Study:

• To review clinical evidence, regimens, patient characteristics, and biological rationale for ICI rechallenge in HCC.
• To summarize current strategies and outcomes of ICI rechallenge.
• To highlight future research directions for optimizing ICI rechallenge.

Main Methods:

• Comprehensive literature review of clinical studies on ICI rechallenge for HCC.
• Analysis of different rechallenge strategies, including combinations with targeted therapy and dual ICIs.
• Examination of patient factors associated with clinical benefits and mechanistic insights.

Main Results:

• Four main ICI rechallenge strategies identified, often involving targeted therapy with anti-PD-L1 or dual ICIs.
• ICI rechallenge demonstrated variable but notable antitumor activity and an acceptable safety profile.
• Benefits were more frequent in patients with preserved liver function, younger age, and lower tumor burden, though heterogeneity exists.

Conclusions:

• ICI rechallenge is a rational option for selected HCC patients, offering additional clinical benefit.
• Immune-related adverse events (irAEs) may increase but are generally manageable.
• Future research should focus on optimizing regimens, biomarkers, and understanding molecular mechanisms for personalized strategies.