Baseline Predictors, Prognostic Impact, and Risk Stratification of Early Progressive Disease on Atezolizumab-Bevacizumab in Unresectable Hepatocellular Carcinoma: A Multicenter Real-World Study.
13 affiliations
- 1Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
- 2Division of Internal medicine, Department of Gastroenterology and Hepatology, Iwate Medical University, Morioka, Japan.
- 3Divison of Gastroenterology, Tohoku University Hospital, Sendai, Japan.
- 4Aomori Prefectural Central Hospital, Aomori, Japan.
- 5Department of Gastroenterology, Hematology and Clinical immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
- 6Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.
- 7Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan.
- 8Department of Gastroenterology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
- 9Hakodate City Hospital, Hakodate, Japan.
- 10Department of Gastroenterology and Hepatology, Japan Community Health Care Organization (JCHO) Hokkaido Hospital, Sapporo, Japan.
- 11Hokkaido Gastroenterology Hospital, Sapporo, Japan.
- 12Japanese Red Cross Morioka Hospital, Morioka, Japan.
- 13Department of Gastroenterology, NHO Sendai Medical Center, Sendai, Japan.
Abstract
Introduction
Early progressive disease (early PD) at the first imaging assessment during atezolizumab plus bevacizumab (Atezo/Bev) therapy may represent primary resistance and is associated with poor outcomes in unresectable hepatocellular carcinoma (uHCC). This study aimed to quantify the frequency, prognostic impact, and baseline predictors of early PD in a large real-world cohort.Methods
Consecutive patients with uHCC who initiated Atezo/Bev therapy at 28 institutions in Japan (September 2020-August 2025) were retrospectively analyzed. Early PD was defined as PD at the first on-treatment imaging assessment, according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Overall survival (OS) was compared using Kaplan-Meier analysis. Baseline predictors were examined using prespecified multivariable logistic regression with multiple imputation: the primary multivariable model included Barcelona Clinic Liver Cancer (BCLC) stage C and alpha-fetoprotein (AFP) ≥400 ng/mL, while an alternative tumor-feature model including extrahepatic spread (EHS) and macrovascular invasion (MVI) was evaluated as a sensitivity analysis.Results
Among 685 treated patients, 666 were evaluable at the first imaging assessment, of whom 148 (22.2%) had early PD. The median OS was 333 days in the early-PD group versus 768 days in the non-early-PD group (log-rank p < 0.001). In the primary multivariable model, AFP ≥ 400 ng/mL (OR 2.33, 95% confidence interval [CI]: 1.58-3.43) and BCLC-C (OR 1.76, 95% CI: 1.15-2.68) independently predicted early PD. In the alternative tumor-feature model, AFP ≥ 400 ng/mL (OR 2.50, 95% CI: 1.69-3.69) and EHS (OR 1.52, 95% CI: 1.03-2.23) remained significant predictors, whereas MVI did not. Two-point baseline scores (AFP ≥ 400 plus BCLC-C or EHS) stratified the risk of early PD in a stepwise manner, reaching approximately 40% in the highest-risk group (p for trend < 0.001).Conclusion
Early PD occurs in approximately one-fifth of patients with uHCC treated with Atezo/Bev and is associated with markedly poorer OS. AFP ≥ 400 ng/mL and BCLC-C provide a pragmatic baseline risk stratification approach that may help guide early monitoring and treatment sequencing.
Related
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- Real-world evidence for atezolizumab with bevacizumab for unresectable hepatocellular carcinoma: a multicentre UK Midlands cohort
- Curative Locoregional Therapy following Objective Response to Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma.
- Baseline Host Biomarkers and Six-Month Sustained Drug-Free Status After Atezolizumab–Bevacizumab for Hepatocellular Carcinoma: Exploratory Clinical Stratification Using PAN-DF Score
- Acute colonic variceal bleeding treated with coil-assisted retrograde transvenous obliteration following atezolizumab-bevacizumab therapy for advanced hepatocellular carcinoma: A case report.
BibTeX
@article{sho2026baseline,
title = {{Baseline Predictors, Prognostic Impact, and Risk Stratification of Early Progressive Disease on Atezolizumab-Bevacizumab in Unresectable Hepatocellular Carcinoma: A Multicenter Real-World Study.}},
author = {Takuya Sho and Goki Suda and Tamami Abe and Masashi Ninomiya and Kei Endo and Yudai Fujiwara and Hiroshi Numao and Go Igarashi and Mio Tsuruoka and Chikara Iino and Kenta Yoshida and Satoshi Sato and Masato Nakai and Masatsugu Ohara and Takashi Kitagataya and Naoki Kawagishi and Tomohiro Katsumi and Keita Maki and Wataru Sato and Shinichiro Minami and Kazumichi Abe and Masashi Fujita and Yoshiya Yamamoto and Masaru Baba and Takashi Meguro and Takayoshi Oikawa and Nobukazu Tanabe and Yoshiyuki Ueno and Naoya Sakamoto and Hidekatsu Kuroda and for NORTH Japan HCC study group},
journal = {Liver cancer},
year = {2026},
month = aug,
doi = {10.1159/lic/admag005},
url = {https://europepmc.org/article/MED/42923551},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Baseline Predictors, Prognostic Impact, and Risk Stratification of Early Progressive Disease on Atezolizumab-Bevacizumab in Unresectable Hepatocellular Carcinoma: A Multicenter Real-World Study.
AU - Takuya Sho
AU - Goki Suda
AU - Tamami Abe
AU - Masashi Ninomiya
AU - Kei Endo
AU - Yudai Fujiwara
AU - Hiroshi Numao
AU - Go Igarashi
AU - Mio Tsuruoka
AU - Chikara Iino
AU - Kenta Yoshida
AU - Satoshi Sato
AU - Masato Nakai
AU - Masatsugu Ohara
AU - Takashi Kitagataya
AU - Naoki Kawagishi
AU - Tomohiro Katsumi
AU - Keita Maki
AU - Wataru Sato
AU - Shinichiro Minami
AU - Kazumichi Abe
AU - Masashi Fujita
AU - Yoshiya Yamamoto
AU - Masaru Baba
AU - Takashi Meguro
AU - Takayoshi Oikawa
AU - Nobukazu Tanabe
AU - Yoshiyuki Ueno
AU - Naoya Sakamoto
AU - Hidekatsu Kuroda
AU - for NORTH Japan HCC study group
PY - 2026
DA - 2026/08/20
JO - Liver cancer
DO - 10.1159/lic/admag005
UR - https://europepmc.org/article/MED/42923551
AB - Introduction Early progressive disease (early PD) at the first imaging assessment during atezolizumab plus bevacizumab (Atezo/Bev) therapy may represent primary resistance and is associated with poor outcomes in unresectable hepatocellular carcinoma (uHCC). This study aimed to quantify the frequency, prognostic impact, and baseline predictors of early PD in a large real-world cohort.Methods Consecutive patients with uHCC who initiated Atezo/Bev therapy at 28 institutions in Japan (September 2020-August 2025) were retrospectively analyzed. Early PD was defined as PD at the first on-treatment imaging assessment, according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Overall survival (OS) was compared using Kaplan-Meier analysis. Baseline predictors were examined using prespecified multivariable logistic regression with multiple imputation: the primary multivariable model included Barcelona Clinic Liver Cancer (BCLC) stage C and alpha-fetoprotein (AFP) ≥400 ng/mL, while an alternative tumor-feature model including extrahepatic spread (EHS) and macrovascular invasion (MVI) was evaluated as a sensitivity analysis.Results Among 685 treated patients, 666 were evaluable at the first imaging assessment, of whom 148 (22.2%) had early PD. The median OS was 333 days in the early-PD group versus 768 days in the non-early-PD group (log-rank p < 0.001). In the primary multivariable model, AFP ≥ 400 ng/mL (OR 2.33, 95% confidence interval [CI]: 1.58-3.43) and BCLC-C (OR 1.76, 95% CI: 1.15-2.68) independently predicted early PD. In the alternative tumor-feature model, AFP ≥ 400 ng/mL (OR 2.50, 95% CI: 1.69-3.69) and EHS (OR 1.52, 95% CI: 1.03-2.23) remained significant predictors, whereas MVI did not. Two-point baseline scores (AFP ≥ 400 plus BCLC-C or EHS) stratified the risk of early PD in a stepwise manner, reaching approximately 40% in the highest-risk group (p for trend < 0.001).Conclusion Early PD occurs in approximately one-fifth of patients with uHCC treated with Atezo/Bev and is associated with markedly poorer OS. AFP ≥ 400 ng/mL and BCLC-C provide a pragmatic baseline risk stratification approach that may help guide early monitoring and treatment sequencing.
SN - 2235-1795
SN - 1664-5553
ER -