Simplified BALAD (BALAD‐S) Score as a Guide for First‐Line Immune Checkpoint Inhibitor Selection for Unresectable Hepatocellular Carcinoma

Background and Aim Atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre) are widely used first‐line immune checkpoint inhibitor (ICI)‐based regimens for unresectable hepatocellular carcinoma (uHCC). However, reliable biomarkers to inform treatment choice remain limited. This study evaluated whether the simplified BALAD‐based score (BALAD‐S) is associated with differential treatment outcomes. Materials and Methods This multicenter retrospective study included 752 Japanese patients with uHCC who received first‐line Atez/Bev ( n = 645) or Dur/Tre ( n = 107) between October 2020 and March 2026. BALAD‐S was calculated using bilirubin, albumin, AFP, AFP‐L3, and des‐γ‐carboxy prothrombin, and patients were stratified into BALAD‐S low (≤ 2) and high (≥ 3) groups. Treatment response, progression‐free survival (PFS), and overall survival (OS) were evaluated. Results In the BALAD‐S low group, Atez/Bev showed longer PFS than Dur/Tre (10.5 vs. 4.3 months; p < 0.001), with longer OS also observed (28.3 vs. 19.4 months; p = 0.049). In the BALAD‐S high group, PFS did not differ significantly (7.0 vs. 5.3 months with Dur/Tre and Atez/Bev, respectively, p = 0.210), whereas OS was longer with Dur/Tre than with Atez/Bev (27.3 vs. 16.4 months; p = 0.022). Treatment effects differed by BALAD‐S category (HR for Dur/Tre vs. Atez/Bev: 1.50 in BALAD‐S low and 0.55 in BALAD‐S high; p for interaction = 0.005). In patients treated from 2023 onward, similar treatment‐effect heterogeneity was observed (HR 1.61 in BALAD‐S low and 0.59 in BALAD‐S high; p for interaction = 0.007). Conclusion Outcomes with Atez/Bev and Dur/Tre differed according to BALAD‐S score. BALAD‐S may help identify patients with differential outcomes between first‐line ICI‐based regimens and represents a candidate stratification marker requiring validation.