Simplified BALAD (BALAD-S) Score as a Guide for First-Line Immune Checkpoint Inhibitor Selection for Unresectable...

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.

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.

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).

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.