ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmunology and Therapeutic Innovations in Hepatocellular Carcinoma: Exploring Immune Evasion and BeyondView all 16 articles
Concomitant medication use and clinical outcome in hepatocellular carcinoma treated with immune-based therapy: a multicenter analysis
Provisionally accepted
Jun-Zhe Yi1Jie Xu1
Jiangzheng Zeng2Yu-Jia Song1Yu-Nan Zhang1Cheng-Mou Huang2Lei Li3Ke Ding4Zhi-Jian Zhu5Dao-Zu Yuan6Yu-Wen Fan7Shang-Fu Ning8Xin Liu9Jian-Zhong Zhang10
Yongfei You11Qi Zhou12Hao-Jie Song13Gen-Jun Tan1Xin-Tong Wu1
Rongping Guo1Min-Shan Chen1
Ning Lyu1*
Ming Zhao1*- 1Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
- 2The First Affiliated Hospital of Hainan Medical University, Haikou, China
- 3Guangzhou Chest Hospital, Guangzhou, China
- 4Affiliated Jiangmen Traditional Chinese Medicine Hospital of Jinan University, Jiangmen, China
- 5Ganzhou cancer hospital, Ganzhou, China
- 6Chengdu Medical College Chengdu Seventh People's Hospital, Chengdu, China
- 7Chenzhou Municipal Hospital of Traditional Chinese Medicine, Chenzhou, China
- 8Wuchuan City People's Hospital, Wuchuan, China
- 9Yantai Hospital of Traditional Chinese Medicine, Yantai, China
- 10Yunan County People's Hospital, Yunan, China
- 11Nanchang First Hospital, Nanchang, China
- 12Guangyuan Central Hospital, Guangyuan, China
- 13Boai Hospital of Zhongshan, Zhongshan, China
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Introduction: Immune checkpoint inhibitors (ICIs) have been increasingly used in hepatocellular carcinoma (HCC). Despite emerging evidence indicating that concomitant medications might impact clinical outcomes, their association with ICI efficacy is undefined in HCC. Methods: The multicenter cohort included 851 HCC patients receiving ICIs between January 2018 and December 2022 in 13 institutions. Concomitant medications given within 30 days before or after the initiation of ICIs were evaluated in association with survival, tumor response, and treatment-related adverse event (TRAE) occurrence. Concomitant medications administered within 30 days before or after the initiation of ICI therapy were identified and used to categorize patients into user and non-user groups for each medication class. The primary outcomes were overall survival (OS), and secondary outcomes included progression-free survival (PFS), time to progression (TTP), tumor response, and TRAEs. Tumor response was evaluated based on RECIST 1.1. Multivariable Cox and logistic regression models were used to adjust for confounding variables. Results: The median OS (13.6 vs. 20.7 months; P = 0.006) and PFS (6.6 vs. 8.9 months; P = 0.002) were significantly reduced for antibiotic users compared to non-users, while other drugs did not show an impact on patient outcomes. In multivariable analysis, antibiotic use predicted worse survival outcomes (OS: HR = 1.88, 95% CI, 1.14–3.11; P = 0.014; PFS: HR = 1.60, 95% CI, 1.20–2.13; P = 0.001). Patients who underwent glucocorticoids for early TRAE management achieved longer OS than those for prophylactic use (OS: Not
Keywords: Hepatocellular carcinoma, Immunotherapy, concomitant medication, clinical outcomes, Treatment-related adverse events
Received: 13 Aug 2025; Accepted: 12 Nov 2025.
Copyright: © 2025 Yi, Xu, Zeng, Song, Zhang, Huang, Li, Ding, Zhu, Yuan, Fan, Ning, Liu, Zhang, You, Zhou, Song, Tan, Wu, Guo, Chen, Lyu and Zhao. 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:
Ning Lyu, lvning@sysucc.org.cn
Ming Zhao, zhaoming@mail.sysu.edu.cn
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