Background & 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 longterm survival outcomes. Methods: We conducted a systematic review and meta-analysis of the MEDLINE, Embase, and 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 2,179 patients selected from 12 cohorts, 80.5% were male, median age was 66 years (IQR 61.6-73.0), 61.6% had advanced-stage hepatocellular carcinoma (HCC), and 83.6% were Child-Pugh (CP) class A. Pooled 6-and 12-month OS was 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 was 57% (95% CI: 53-61%; I2 = 49%) and 35% (95% CI: 31-39%, I2 = 60%). Among patients with longer followup, the OS (n = 1,783) 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 =1,556) 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. (c) 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/).

Efficacy of atezolizumab plus bevacizumab for unresectable HCC: Systematic review and meta-analysis of real-world evidence

Rimassa, Lorenza;
2025-01-01

Abstract

Background & 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 longterm survival outcomes. Methods: We conducted a systematic review and meta-analysis of the MEDLINE, Embase, and 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 2,179 patients selected from 12 cohorts, 80.5% were male, median age was 66 years (IQR 61.6-73.0), 61.6% had advanced-stage hepatocellular carcinoma (HCC), and 83.6% were Child-Pugh (CP) class A. Pooled 6-and 12-month OS was 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 was 57% (95% CI: 53-61%; I2 = 49%) and 35% (95% CI: 31-39%, I2 = 60%). Among patients with longer followup, the OS (n = 1,783) 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 =1,556) 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. (c) 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/).
2025
Child–Pugh
HCC
Immunotherapy
RWE
Survival
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/101510
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