Patterns of Response to Durvalumab Plus Tremelimumab and Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma

BACKGROUND/AIM: Immune checkpoint inhibitor-based combination therapies are standard treatment options for unresectable hepatocellular carcinoma (HCC). However, conventional endpoints such as objective response rate, progression-free survival, and overall survival may not fully capture response dynamics, including depth of response (DpR), time to response, and duration of response. This study descriptively evaluated response dynamics in patients with unresectable HCC treated with durvalumab plus tremelimumab or atezolizumab plus bevacizumab. PATIENTS AND METHODS: This retrospective single-center study included 148 patients with unresectable HCC who received durvalumab-tremelimumab (n=53) or atezolizumab-bevacizumab (n=95). A reduction of ≥50% in target lesion diameter was defined as DpR50. Because of baseline imbalances and differences in observation period, the analysis was only descriptive and hypothesis-generating. RESULTS: Fifty-three patients received durvalumab-tremelimumab and 95 received atezolizumab-bevacizumab. The overall response rate was 35.8% for the durvalumab-tremelimumab group and 27.4% for the atezolizumab-bevacizumab group, whereas the disease control rates were 54.7% and 71.6%, respectively. DpR50 was observed in 26.4% and 11.6% of patients, respectively. The median times to response were 2.3 and 3.3 months, and the median durations of response were 22.3 and 10.0 months, respectively. Durable response lasting ≥6 months occurred in 24.5% and 15.8% of all treated patients, respectively. The median PFS was 5.2 and 7.0 months, and median OS was 17.0 and 22.0 months, respectively. CONCLUSION: Therapy with durvalumab-tremelimumab was associated with deeper and more durable tumor shrinkage in selected responders, whereas atezolizumab-bevacizumab provided broader disease control mainly through stable disease. These findings should be interpreted as hypothesis-generating.