Efficacy of atezolizumab plus bevacizumab for unresectable HCC: systematic review and metanalysis of real-world evidence
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background and Aims
Atezolizumab plus bevacizumab (A+B) is a standard of care treatment in unresectable hepatocellular carcinoma (uHCC). Verification of its effectiveness outside clinical trials is an area of unmet need, especially in estimating long-term survival outcomes.
Methods
We conducted a systematic review and metanalysis of MEDLINE, Embase, Cochrane libraries to evaluate therapy outcomes in patients treated with frontline A+B for uHCC outside trials. Pooled estimates of overall survival (OS) and progression-free survival (PFS) at 6 and 12 months were calculated from individual patient-level data using random-effects analysis.
Results
Of 2179 patients selected from 12 cohorts, 80.5% were male, median age was 66 years (IQR 61.6-73.0), 61.6% had advanced-stage HCC, and 83.6% were Child-Pugh (CP) class A. Pooled 6- and 12-month OS were 82% (95%CI 76-86%; I2=80%) and 65% (95%CI 60-70%; I2=66%). Median OS of patients with CP-A liver function was 20.9 months (95%CI 15.7-20.9), consistent with IMbrave150 estimates (19.2 months, 95%CI 17.0-23.7, p=0.58). Pooled PFS at 6 and 12 months were 57% (95%CI 53-61%; I2=49%) and 35% (95%CI 31-39%, I2=60%). Among patients with longer follow-up, the OS (n=1783) and PFS (n=959) rates were 52% (95%CI 46-58; I2=90%) and 26% (95%CI 17-37; I2=91%) at 18 months, respectively. At 24-months, OS (n=1556) rate was 39% (95%CI 31-49; I2=90%) and PFS (n=732) rate was 25% (95%CI 12-45; I2=95%).
Conclusions
The effectiveness of A+B after registration mirrors its efficacy estimates from clinical trial datasets. Long-term survival at 24 months can be achieved in up to 39% of patients with uHCC treated with A+B in routine clinical practice.
Impact and implications
This study provides real-world evidence supporting the long-term efficacy of atezolizumab plus bevacizumab (A+B) for unresectable hepatocellular carcinoma (uHCC), showing survival outcomes similar to clinical trials. These findings are important for clinicians in supporting A+B as a frontline treatment, particularly for patients with Child-Pugh class A liver function. They also offer valuable insights for policymakers and researchers in optimizing treatment strategies for uHCC. However, results should be interpreted with caution due to potential variability in patient populations.
Atezolizumab plus bevacizumab (A+B) is a standard of care treatment in unresectable hepatocellular carcinoma (uHCC). Verification of its effectiveness outside clinical trials is an area of unmet need, especially in estimating long-term survival outcomes.
Methods
We conducted a systematic review and metanalysis of MEDLINE, Embase, Cochrane libraries to evaluate therapy outcomes in patients treated with frontline A+B for uHCC outside trials. Pooled estimates of overall survival (OS) and progression-free survival (PFS) at 6 and 12 months were calculated from individual patient-level data using random-effects analysis.
Results
Of 2179 patients selected from 12 cohorts, 80.5% were male, median age was 66 years (IQR 61.6-73.0), 61.6% had advanced-stage HCC, and 83.6% were Child-Pugh (CP) class A. Pooled 6- and 12-month OS were 82% (95%CI 76-86%; I2=80%) and 65% (95%CI 60-70%; I2=66%). Median OS of patients with CP-A liver function was 20.9 months (95%CI 15.7-20.9), consistent with IMbrave150 estimates (19.2 months, 95%CI 17.0-23.7, p=0.58). Pooled PFS at 6 and 12 months were 57% (95%CI 53-61%; I2=49%) and 35% (95%CI 31-39%, I2=60%). Among patients with longer follow-up, the OS (n=1783) and PFS (n=959) rates were 52% (95%CI 46-58; I2=90%) and 26% (95%CI 17-37; I2=91%) at 18 months, respectively. At 24-months, OS (n=1556) rate was 39% (95%CI 31-49; I2=90%) and PFS (n=732) rate was 25% (95%CI 12-45; I2=95%).
Conclusions
The effectiveness of A+B after registration mirrors its efficacy estimates from clinical trial datasets. Long-term survival at 24 months can be achieved in up to 39% of patients with uHCC treated with A+B in routine clinical practice.
Impact and implications
This study provides real-world evidence supporting the long-term efficacy of atezolizumab plus bevacizumab (A+B) for unresectable hepatocellular carcinoma (uHCC), showing survival outcomes similar to clinical trials. These findings are important for clinicians in supporting A+B as a frontline treatment, particularly for patients with Child-Pugh class A liver function. They also offer valuable insights for policymakers and researchers in optimizing treatment strategies for uHCC. However, results should be interpreted with caution due to potential variability in patient populations.
Date Issued
2025-08-01
Date Acceptance
2025-04-15
Citation
JHEP Reports, 2025, 7 (8)
ISSN
2589-5559
Publisher
Elsevier
Journal / Book Title
JHEP Reports
Volume
7
Issue
8
Copyright Statement
© 2025 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). JHEP Reports, 2025, 7, 1–1
Identifier
10.1016/j.jhepr.2025.101431
Publication Status
Published
Article Number
101431
Date Publish Online
2025-04-22