Unresectable Hepatocellular Carcinoma
Conditions
Keywords
Unresectable Hepatocellular Carcinoma, Atezolizumab, Bevacizumab, Unresectable HCC, Locoregional Therapy, TACE, HAIC, TARE, Ablation, Real-world, HBV, Asia-Pacific
Brief summary
This is a retrospective, multicenter, real-world cohort study designed to evaluate the effectiveness and safety of atezolizumab plus bevacizumab (Atezo+Bev) combined with various locoregional therapies (LRTs), including transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), transarterial radioembolization (TARE), ablation, and radiotherapy, in patients with unresectable hepatocellular carcinoma (uHCC). Approximately 1,136 patients treated between October 28, 2020 and October 31, 2025 will be included from about 35 sites across China and the Asia-Pacific region. The primary endpoint is overall survival (OS). Secondary endpoints include real-world progression-free survival (rwPFS), overall response rate (ORR), disease control rate (DCR), time to discontinuation (TTD), time to next treatment (TTNT), time to progression (TTP), and safety outcomes. Exploratory analyses will assess associations between baseline patient characteristics, treatment patterns, and clinical outcomes.
Detailed description
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.
Interventions
OTHERAtezo+Bev plus Locoregional Therapy
Patients received atezolizumab plus bevacizumab (Atezo+Bev) in combination with at least one locoregional therapy (transarterial chemoembolization \[TACE\], hepatic arterial infusion chemotherapy \[HAIC\], transarterial radioembolization \[TARE\], ablation, or radiotherapy) within ±2 months of systemic therapy initiation, in routine clinical practice.
Sponsors
Zhongda Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 36 months (median follow-up period anticipated) | Overall survival, defined as the time from initiation of atezolizumab plus bevacizumab treatment to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 36 months | Proportion of patients with complete response (CR) or partial response (PR), as assessed by RECIST 1.1 and mRECIST criteria. |
| Disease Control Rate (DCR) | Up to 36 months | Proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD ≥6 weeks), based on RECIST 1.1 or mRECIST. |
| Time to Treatment Discontinuation (TTD) | Up to 36 months | Time from treatment initiation to discontinuation of Atezo+Bev for any reason. |
| Real-world Progression-Free Survival (rwPFS) | Up to 36 months | Time from initiation of Atezo+Bev treatment to investigator-assessed disease progression (local progression, recurrence, new metastasis, or clinical progression) or death from any cause. |
| Time to Progression (TTP) | Up to 36 months | Time from initiation of Atezo+Bev to first documentation of disease progression. |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | Up to 36 months | Incidence and severity of all adverse events (AEs), treatment-related AEs (TRAEs), and adverse events of special interest (bleeding, hypertension, hepatic impairment, immune-related AEs). |
| Time to Next Treatment (TTNT) | Up to 36 months | Time from initiation of Atezo+Bev to start of subsequent systemic therapy. |
Countries
China
Outcome results
None listed