Impact of time‐of‐day atezolizumab plus bevacizumab combination therapy infusion for unresectable hepatocellular carcinoma: A retrospective multicenter study

Abstract Aim This study aimed to evaluate the impact of infusion timing of time‐of‐day on clinical outcomes in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab combination therapy. Methods A retrospective analysis was conducted using data from 751 unresectable HCC patients treated with atezolizumab plus bevacizumab between September 2020 and April 2024. Patients were categorized into morning (AM; n = 351) and afternoon (PM; n = 400) groups based on infusion timing of time‐of‐day. Outcomes, including progression‐free survival (PFS), overall survival, objective response rate, and disease control rate, were assessed using Kaplan–Meier survival analysis and Cox regression analysis. Results The PFS was significantly longer in the AM group (8.6 months, 95% CI 7.6–10.5) compared with the PM group (6.0 months, 95% CI 5.4–7.0; p = 0.006). In contrast, overall survival was similar between the groups (AM: 24.7 months vs. PM: 21.4 months; p = 0.99). Cox regression analysis revealed that morning infusion was an independent favorable predictor of PFS (HR 1.23, 95% CI 1.04–1.45). Additionally, the AM group demonstrated superior objective response rate and disease control rate compared with the PM group, suggesting better tumor control. Conclusion Morning infusion of atezolizumab plus bevacizumab is associated with improved PFS and response rates in unresectable HCC patients, highlighting the potential for optimizing treatment outcomes through circadian timing.