ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1599143
On-Treatment modified Glasgow Prognostic Score (mGPS) in hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab provides prognostic information
Provisionally accepted
Tessa Hattenhauer
Rebekka Mispelbaum*
Annkristin Heine
Katjana Schwab
Peter BrossartNiklas KlümperJonas Saal*- University Hospital Bonn, Bonn, Germany
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Background & Aims Hepatocellular carcinoma (HCC) is associated with high cancer-specific mortality. While immune-checkpoint inhibitors (ICIs) improved overall survival (OS) compared to tyrosine kinase inhibitors, biomarkers predicting response to ICI in HCC are lacking. This study investigates the prognostic value of serum-based prognostic scores in patients with HCC receiving atezolizumab and bevacizumab. Methods This post-hoc study analysis evaluates data from the phase 3 IMbrave150 trial, comparing atezolizumab plus bevacizumab to sorafenib in patients with unresectable HCC. 212 patients were included in the analysis. The prognostic value of imaging was compared to albumin, C-reactive protein (CRP) and interleukin-6 (IL-6), as well as composite scores, including the modified Glasgow Prognostic Score (mGPS) after three cycles of therapy. For further analysis, patients were classified in three risk groups according to each scoring system (low-risk, intermediate-risk and high-risk). Results The on-treatment mGPS, assessed 9 weeks post-treatment initiation, predicted OS with hazard ratios of 2.31 (95% CI 1.39–3.83, p < 0.001) for intermediate-risk and 3.40 (95% CI 3.07–5.59, p < 0.001) for high-risk, compared to low-risk groups, showing greater accuracy than RECIST imaging. Albumin, CRP, and IL-6 were individually good prognostic indicators, with albumin/CRP (ACR) and albumin/IL-6 (AIR) ratios having the highest prognostic power (c-index: ACR 0.66 (95% CI 0.61–0.71), AIR 0.67 (0.62–0.72), mGPS 0.62 (0.57–0.66)). Multivariable analysis confirmed serum-based scores' prognostic value independent of imaging. Serum-based scores significantly correlated with survival in patients with stable disease (SD, 79% of patients) or progressive disease (PD, 12% of patients). Conclusions The on-treatment mGPS, as well as ACR and AIR, predicted outcomes in patients with HCC independent of and more accurately than radiological staging. Since, the mGPS is the most cost effective and widely validated score, we consider it best suited for clinical use. Prospective validation is needed to confirm these findings.
Keywords: HCC, biomarkers, Immunotherapy, Checkpoint-Inhibition, mGPS
Received: 24 Mar 2025; Accepted: 05 Sep 2025.
Copyright: © 2025 Hattenhauer, Mispelbaum, Heine, Schwab, Brossart, Klümper and Saal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Rebekka Mispelbaum, University Hospital Bonn, Bonn, Germany
Jonas Saal, University Hospital Bonn, Bonn, Germany
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