Efficacy and Safety of Atezolizumab Plus Bevacizumab Versus Durvalumab Plus Tremelimumab for Unresectable Hepatocellular Carcinoma in Patients With Child–Pugh Class B: A Real‐World Study

ABSTRACT Aim Evidence regarding the optimal first‐line immune checkpoint inhibitor (ICI) regimen for treating unresectable hepatocellular carcinoma (uHCC) with Child–Pugh class B (CP‐B) liver function remains limited. This study compared atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre group) in real‐world settings. Methods In this multicenter retrospective study, 211 consecutive patients with uHCC and CP‐B liver function who underwent ICI‐based therapy as a first‐line therapy were analyzed. Treatment responses, survival outcomes, albumin–bilirubin (ALBI) score changes, and adverse events were evaluated. Survival analyses were adjusted using inverse probability weighting (IPW). Results The median progression‐free survival associated with the Atez/Bev and Dur/Tre regimens was 5.0 and 3.5 months, respectively; the median corresponding overall survival was 10.5 and 12.4 months. After IPW adjustment, no significant differences were observed in progression‐free or overall survival. The Atez/Bev regimen‐associated disease control rate was significantly higher (75.2% vs. 55.0%, p = 0.02). The Dur/Tre regimen, meanwhile, was associated with a significantly higher immune‐related adverse event incidence (10.5% vs. 32.7%, p < 0.01) and a greater need for high‐dose corticosteroid treatment. In contrast, the Atez/Bev regimen resulted in a progressive decrease in ALBI scores, whereas the Dur/Tre regimen maintained the hepatic functional reserve. Conclusions The Atez/Bev and Dur/Tre regimens afforded comparable survival outcomes but differed substantially in safety and effects on the hepatic functional reserve. Given the trade‐off between immunotoxicity and liver function preservation, treatment selection for CP‐B liver function should be individualized, considering baseline hepatic reserve, tolerability, and anticipated treatment trajectory.