Three-year overall survival in unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Masatsugu Ohara^#¹, Goki Suda^#², Risako Kohya¹, Yutaka Yasui³, Kaoru Tsuchiya³, Masayuki Kurosaki³, Joji Tani⁴, Shinya Maekawa⁵, Nobuyuki Enomoto⁵, Makoto Chuma^{6

7}, Manabu Morimoto⁶, Shun Kaneko⁸, Mina Nakagawa⁸, Yasuhiro Asahina^{8

9}, Atsumasa Komori¹⁰, Yuki Kugiyama¹⁰, Masaru Baba¹¹, Akihisa Nakamura¹², Jun Ito¹³, Ren Yamada¹⁴, Shunichi Hosoda¹, Yoshiya Yamamoto¹⁵, Sonoe Yoshida¹, Takuya Sho¹, Takashi Sasaki¹, Tomoka Yoda¹, Akimitsu Meno¹, Naohiro Yasuura¹, Qingjie Fu¹, Zijian Yang¹, Osamu Maehara¹⁶, Shunsuke Ohnishi¹⁶, Yoshimasa Tokuchi¹, Takashi Kitagataya¹, Naoki Kawagishi¹, Masato Nakai¹, Koji Ogawa¹, Naoya Sakamoto¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.
² Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan. gsudgast@pop.med.hokudai.ac.jp.
³ Department of Gastroenterology, Hepatology Musashino Red Cross Hospital, Tokyo, Japan.
⁴ Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan.
⁵ Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Kofu, Japan.
⁶ Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
⁷ Gastroenterological Center, JCHO Yokohama Hodogaya Central Hospital, Yokohama, Japan.
⁸ Department of Gastroenterology and Hepatology, Institute of Science Tokyo (Science Tokyo), Tokyo, Japan.
⁹ Division of Hepatic Medical Science, Institute of Science Tokyo (Science Tokyo), Tokyo, Japan.
¹⁰ Hepatology Division, NHO Nagasaki Medical Centre, Ōmura, Japan.
¹¹ Centre for Gastroenterology and Hepatology, Japan Community Healthcare Organisation Hokkaido Hospital, Sapporo, Japan.
¹² Department of Gastroenterology, Kitami Red Cross Hospital, Kitami, Japan.
¹³ Department of Gastroenterology and Hepatology, NHO Hokkaido Medical Centre, Sapporo, Japan.
¹⁴ Kushiro Rosai Hospital, Kushiro, Japan.
¹⁵ Department of Gastroenterology and Hepatology, Hakodate Municipal Hospital, Hakodate, Japan.
¹⁶ Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.

^# Contributed equally.

PMID: 40875102
DOI: 10.1007/s12072-025-10875-7

Three-year overall survival in unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Masatsugu Ohara et al. Hepatol Int. 2025.

. 2025 Aug 28.

doi: 10.1007/s12072-025-10875-7. Online ahead of print.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.
² Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan. gsudgast@pop.med.hokudai.ac.jp.
³ Department of Gastroenterology, Hepatology Musashino Red Cross Hospital, Tokyo, Japan.
⁴ Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan.
⁵ Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Kofu, Japan.
⁶ Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
⁷ Gastroenterological Center, JCHO Yokohama Hodogaya Central Hospital, Yokohama, Japan.
⁸ Department of Gastroenterology and Hepatology, Institute of Science Tokyo (Science Tokyo), Tokyo, Japan.
⁹ Division of Hepatic Medical Science, Institute of Science Tokyo (Science Tokyo), Tokyo, Japan.
¹⁰ Hepatology Division, NHO Nagasaki Medical Centre, Ōmura, Japan.
¹¹ Centre for Gastroenterology and Hepatology, Japan Community Healthcare Organisation Hokkaido Hospital, Sapporo, Japan.
¹² Department of Gastroenterology, Kitami Red Cross Hospital, Kitami, Japan.
¹³ Department of Gastroenterology and Hepatology, NHO Hokkaido Medical Centre, Sapporo, Japan.
¹⁴ Kushiro Rosai Hospital, Kushiro, Japan.
¹⁵ Department of Gastroenterology and Hepatology, Hakodate Municipal Hospital, Hakodate, Japan.
¹⁶ Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.

^# Contributed equally.

PMID: 40875102
DOI: 10.1007/s12072-025-10875-7

Abstract

Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality. Although the atezolizumab/bevacizumab regimen demonstrated impressive efficacy in the IMbrave150 clinical trial, long-term outcomes, particularly 3-year overall survival (OS), remain unestablished because of limited follow-up. Long-term outcomes have been reported for the tremelimumab/durvalumab combination, highlighting the need for comparable data on atezolizumab/bevacizumab. We aimed to elucidate the 3-year OS in patients with unresectable HCC (uHCC) treated with atezolizumab plus bevacizumab.

Methods: This retrospective multicenter study included patients with uHCC who received atezolizumab/bevacizumab. Among the 506 patients treated at the participating institutions, only those who initiated therapy between October 2020 and January 2022 were included. Comprehensive clinical, laboratory, and imaging data were collected, and the patients were followed up until March 2025.

Results: A total of 257 patients were analyzed, with a median follow-up of 48.23 months (range, 36.23-53.60 months). The 2- and 3-year OS rates were 39.2% and 25.3%, respectively. Among patients meeting the IMbrave150 criteria, the 3-year OS rate was 31.6%. Multivariate regression analysis identified baseline alpha-fetoprotein level > 116 ng/mL (odds ratio [OR] 0.41; 95% confidence interval [CI] 0.20-0.84; p = 0.015) and modified albumin-bilirubin grade 1-2a (OR 2.50; 95% CI 1.18-5.32; p = 0.017) as significant factors associated with 3-year OS.

Conclusions: In a real-world setting, the 3-year OS for uHCC patients treated with atezolizumab/bevacizumab was 25.3%, rising to 31.6% among those meeting the IMbrave150 criteria. Survival outcomes underscore the clinical value of atezolizumab/bevacizumab in improving long-term prognosis and guiding first-line treatment decisions for patients with unresectable HCC.

Keywords: Biomarker; Cancer; Disease progression; Liver; Long-term survival; Malignancy; Oncology outcomes; Real-world evidence; Retrospective study; Treatment efficacy.

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Conflict of interest statement

Declarations. Conflict of interest: Prof. Naoya Sakamoto received lecture fees from Chugai Pharmaceutical Co., Ltd., and research grants from Gilead Sciences, Inc., and AbbVie, Inc. Dr. Goki Suda received research grants from Gilead Sciences. Prof. Atsumasa Komori received a research grant from Chugai Pharmaceutical Co., Ltd. Prof. Masayuki Kurosaki received honoraria for lecture from Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca, Gilead Sciences, and AbbVie, Inc. Dr. Kaoru Tsuchiya received honoraria for lecture from Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca, and Takeda Pharmaceuticals. Dr. Yutaka Yasui received honoraria for lecture from Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca, and Eli Lilly Japan K.K. All remaining authors have declared no conflicts of interest. Informed consent: The study protocol followed the ethical guidelines of the Declaration of Helsinki, and all participating patients provided informed consent. This study was approved by the ethics committee of Hokkaido University Hospital (020–0267) and the committee of each participating institution.

Comment in

Comments on "Three‑year overall survival in unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab".
Zhang Q, Tian G. Zhang Q, et al. Hepatol Int. 2025 Dec 9. doi: 10.1007/s12072-025-10991-4. Online ahead of print. Hepatol Int. 2025. PMID: 41366187 No abstract available.

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Three-year overall survival in unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Affiliations

Three-year overall survival in unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

References

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