Selecting Frontline Immunotherapy Based on Liver Function and Patient Fitness

This segment focuses on the practical considerations that guide selection among frontline immunotherapy-based regimens for advanced HCC, particularly in relation to liver reserve, toxicity risk, and patient support systems. Dr. Braiteh acknowledges that although pivotal trials such as CheckMate 9DW, HIMALAYA, and IMbrave150 established multiple effective first-line options, concerns about immune-related toxicity, especially with dual checkpoint blockade, can influence real-world adoption.

Dr. Braiteh explains that, beyond TKIs, clinicians often choose between atezolizumab plus bevacizumab, the STRIDE regimen, or nivolumab plus ipilimumab. However, distinguishing which patients are best suited for each approach can be challenging. He highlights that higher-grade or more frequent adverse events observed with nivolumab–ipilimumab may make this regimen less appealing for patients with limited social support, difficulty attending frequent visits, or borderline liver function. Although most trials enrolled patients with Child-Pugh A disease, he notes that clinicians frequently treat patients who fall closer to Child-Pugh B7 in everyday practice, despite limited objective tools beyond measures such as the albumin-bilirubin (ALBI) score.

Dr. Akçe reviews the subgroup analyses from CheckMate 9DW and the HIMALAYA trial that stratified outcomes by baseline ALBI grade. He explains that patients with ALBI grade 1 or 2 liver function derived meaningful survival and response benefits from both nivolumab plus ipilimumab and the STRIDE regimen compared with tyrosine kinase inhibitors. These findings suggest that patients with mild liver dysfunction may still be appropriate candidates for immunotherapy-based combinations.

The discussion then turns to the persistent evidence gap in patients with more advanced hepatic impairment. Dr. Akce emphasizes that prospective data remain limited for patients with Child-Pugh B8 or B9 disease, with only small phase 2 studies available. For patients with Child-Pugh C disease, both experts agree that supportive care and quality-of-life–focused management remain the primary recommendations, underscoring the need for further research in this vulnerable population.