Supplementary Material for: Adverse Event Monitoring with Imaging: Prognostic Significance in Atezolizumab Plus Bevacizumab Therapy for Unresectable Hepatocellular Carcinoma

Background/Aim: Immune checkpoint inhibitors (ICIs) have emerged as the first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). Emerging evidence suggests that immune-related adverse events (irAEs) may be associated with improved ICI efficacy. This study evaluated the impact of adverse events during atezolizumab plus bevacizumab therapy on clinical outcomes in patients with unresectable HCC.
Methods: This retrospective study included consecutive patients receiving first-line atezolizumab plus bevacizumab for unresectable HCC. IrAEs and bevacizumab-related adverse events were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 5.0). Imaging studies conducted during treatment were reviewed to identify asymptomatic, imaging-detected adverse events. Overall survival (OS) was the primary endpoint and was analyzed using time-dependent Cox regression. The secondary endpoint was the disease control rate (DCR).
Results: Among the 198 enrolled patients, 12 had imaging-detected irAEs without symptoms (asymptomatic AE group), whereas 56 experienced clinical symptoms of irAEs (n=28), bevacizumab-related adverse events (n=19) or both (n=9) (symptomatic AE group). The OS rates at 6, 12, 18, and 24 months were 100.0%, 82.5%, 82.5%, and 82.5%, respectively, in the asymptomatic AE group; 89.1%, 64.1%, 41.7%, and 40.5%, respectively, in the symptomatic AE group; and 72.3%, 48.3%, 31.3%, and 19.4%, respectively, for the non-AE group. Compared with the non-AE group, both the asymptomatic and symptomatic AE groups showed significantly improved OS in the inverse probability of treatment weighting-adjusted time-dependent Cox regression analysis (P=0.02). The DCR was significantly greater in the asymptomatic AE group (100.0%) and the symptomatic AE group (91.8%) than in the non-AE group (60.0%) (P<0.001).
Conclusion: Adverse events during atezolizumab plus bevacizumab therapy are associated with improved OS and treatment response in unresectable HCC patients. Asymptomatic imaging-detected irAEs may serve as prognostic factors, highlighting the value of proactive imaging in patient management.