Baseline DCP May Modify Response to Atezolizumab-Bevacizumab Versus Durvalumab-Tremelimumab in Unresectable HCC

For unresectable hepatocellular carcinoma (HCC), atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre) are widely used first-line immunotherapies; however, biomarkers to guide regimen selection before treatment initiation remain undefined. We investigated whether baseline des-γ-carboxy prothrombin (DCP) modifies objective response rate (ORR) according to treatment regimen.

We analysed 1464 patients with unresectable HCC treated with first-line systemic therapy between 2020 and 2025 across multiple centers. Patients were divided into training and validation cohorts. Restricted cubic spline-based interaction models were used to evaluate the association between baseline DCP and ORR according to treatment regimen. The predicted absolute difference in ORR (ΔORR) between regimens was examined across continuous DCP values, with a prespecified 10% threshold considered clinically meaningful. Robustness was assessed using leave-one-center-out and repeated random-split sensitivity analyses.

Overall ORR did not differ significantly between Atez/Bev and Dur/Tre. However, a significant interaction between baseline DCP and treatment regimen was observed in both cohorts. Atez/Bev showed a relatively stable ORR across DCP concentrations, whereas Dur/Tre showed a DCP-dependent increase in ORR. At low DCP levels, Atez/Bev was favoured; with increasing DCP levels, the relative benefit shifted toward Dur/Tre. Sensitivity analyses confirmed a consistent DCP-dependent transition pattern, although the DCP level at which ΔORR exceeded 10% varied across analyses, supporting a transition zone rather than a fixed cutoff.

Baseline DCP may modify the relative treatment benefit between Atez/Bev and Dur/Tre in unresectable HCC. Rather than defining a rigid cutoff, DCP appears to delineate a continuum in which higher levels increasingly favour Dur/Tre, providing a practical framework for individualized immunotherapy selection.