Clinical Determinants Influencing First-line Immune Checkpoint Inhibitor Selection for Unresectable Hepatocellular Carcinoma in Japan.

BACKGROUND/AIM: The lack of direct comparative trials makes selection of immune checkpoint inhibitor (ICI)-based combination regimens for advanced unresectable hepatocellular carcinoma (uHCC) challenging. Consequently, this study aimed to identify the clinical factors influencing the choice between atezolizumab plus bevacizumab (ATEZO-BEV) and tremelimumab plus durvalumab (STRIDE) in real-world clinical setting in Japan.

PATIENTS AND

METHODS

This retrospective observational study analyzed 2,637 patients with uHCC who received first-line ICI-based therapy (ATEZO-BEV or STRIDE) at hospitals affiliated with the National Hospital Organization (NHO) of Japan between April 2023 and September 2024. Patient demographics, comorbidities, concomitant medications, and laboratory values were retrieved from the nationwide NHO clinical data archives. Multivariable logistic regression was performed to identify factors associated with regimen selection.

RESULTS

Out of the 2,637 patients, 2,027 (76.9%) received ATEZO-BEV and 610 (23.1%) received STRIDE. Multivariable analysis revealed that male sex [adjusted odds ratio (aOR)=2.73; p<0.001], total activities of daily living (ADL) score ≧20 (aOR=1.59; p<0.01), use of antihypertensive agents (aOR=1.23; p=0.04), and use of antiplatelet agents or anticoagulants (aOR=1.47; p<0.001) were significantly associated with STRIDE selection, whereas liver cirrhosis (aOR=0.57; p<0.01) was highly associated with a lower likelihood of receiving STRIDE.

CONCLUSION

Total ADL score of ≥20, liver cirrhosis, and concomitant medication patterns significantly influenced the choice between STRIDE and ATEZO-BEV. These findings highlight the importance of individualized, context-dependent decision-making in uHCC treatment, supporting further prospective comparisons to guide optimal therapy.