Atezolizumab Plus Bevacizumab Combined With Locoregional Therapies in Unresectable Hepatocellular Carcinoma (ISMIO-001)

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide, with a particularly high burden in China and the Asia-Pacific region, where chronic hepatitis B virus (HBV) infection is the predominant etiology. While atezolizumab plus bevacizumab (Atezo+Bev) has been established as the global first-line standard of care for unresectable HCC (uHCC), clinical trial populations were highly selective, excluding patients with impaired liver function or poor performance status, and the overall response rate remains limited at approximately 30%.

Locoregional therapies (LRTs) such as TACE, HAIC, TARE, ablation, and radiotherapy remain an integral part of uHCC management in the Asia-Pacific region, offering potential synergistic effects when combined with Atezo+Bev. However, there is a lack of robust real-world evidence describing the timing, sequencing, and outcomes of these combined strategies.

The ISMIO-001 study is designed as a retrospective, multicenter, real-world cohort study. Eligible patients must be ≥18 years old, diagnosed with uHCC, and treated with Atezo+Bev plus at least one LRT within ±2 months of Atezo+Bev initiation, between October 28, 2020 and July 31, 2025. The observation period will continue until October 31, 2025, with study completion anticipated by December 31, 2026.

The study will provide large-scale evidence on treatment patterns, overall survival, safety, and subgroup outcomes (e.g., by BCLC/CNLC stage, Child-Pugh class, ALBI grade, HBV vs. other etiologies). Findings will inform future clinical guidelines and support the optimization of treatment sequencing for uHCC in HBV-predominant populations.

Inclusion criteria

• Age ≥18 years at initiation of atezolizumab plus bevacizumab (Atezo+Bev)
• Histologically or radiologically confirmed unresectable hepatocellular carcinoma (uHCC) according to national guidelines
• Initiated first-line Atezo+Bev treatment between October 28, 2020 and July 31, 2025
• Received ≥1 locoregional therapy (TACE, HAIC, TARE, ablation, or radiotherapy) within ±2 months of Atezo+Bev initiation
• At least one follow-up record available after treatment initiation

Exclusion criteria

• Prior systemic therapy for HCC before Atezo+Bev initiation
• Concurrent participation in interventional clinical trials at baseline
• Diagnosis of other malignancies at baseline (except basal cell carcinoma of the skin)