Cheng Z, Yue AM. Efficacy of regorafenib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis. World J Gastrointest Oncol 2026; 18(1): 113816 [PMID: 41607763 DOI: 10.4251/wjgo.v18.i1.113816]
Corresponding Author of This Article
Ai-Min Yue, MD, Department of Surgical Oncology, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, No. 56 Jinsui Avenue, Xinxiang 453000, Henan Province, China. yueaimin2025@163.com
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Gastroenterology & Hepatology
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Meta-Analysis
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jan 15, 2026 (publication date) through Feb 4, 2026
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World Journal of Gastrointestinal Oncology
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1948-5204
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Cheng Z, Yue AM. Efficacy of regorafenib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis. World J Gastrointest Oncol 2026; 18(1): 113816 [PMID: 41607763 DOI: 10.4251/wjgo.v18.i1.113816]
World J Gastrointest Oncol. Jan 15, 2026; 18(1): 113816 Published online Jan 15, 2026. doi: 10.4251/wjgo.v18.i1.113816
Efficacy of regorafenib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis
Zhang Cheng, Ai-Min Yue
Zhang Cheng, The Fourth Clinical College of Xinxiang Medical University, Xinxiang 453000, Henan Province, China
Ai-Min Yue, Department of Surgical Oncology, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang 453000, Henan Province, China
Author contributions: Cheng Z and Yue AM contributed to the conceptualization and methodology of the study; Cheng Z was responsible for data curation, formal analysis, software development, and resource acquisition, the original draft writing, review and editing of the manuscript. All authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ai-Min Yue, MD, Department of Surgical Oncology, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, No. 56 Jinsui Avenue, Xinxiang 453000, Henan Province, China. yueaimin2025@163.com
Received: September 4, 2025 Revised: October 12, 2025 Accepted: November 24, 2025 Published online: January 15, 2026 Processing time: 130 Days and 21.1 Hours
Abstract
BACKGROUND
Regorafenib is approved as a second-line treatment for advanced hepatocellular carcinoma (HCC), but its comparative efficacy remains under evaluation.
AIM
To evaluate the efficacy and safety of regorafenib vs other second-line therapies in advanced HCC.
METHODS
This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. A comprehensive search of PubMed, EMBASE, Web of Science, and the Cochrane Library was performed on June 6, 2025. Studies were included if they reported at least one relevant clinical outcome: Overall survival, progression-free survival, objective response rate, or disease control rate. Data was extracted independently by two reviewers. Quality was assessed using the Cochrane Risk of Bias 2.0 tool for randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies. Pooled effect estimates were calculated using random- or fixed-effects models depending on the degree of heterogeneity. Sensitivity analyses and Egger’s test were performed to evaluate the robustness of the results and potential publication bias.
RESULTS
Nine studies met inclusion criteria. Regorafenib significantly improved overall survival compared to controls [weighted mean difference = 2.54 months; 95% confidence interval (CI): 0.26-4.81; P < 0.05], but no significant benefit was observed for progression-free survival (weighted mean difference = 1.04; 95%CI: -1.27 to 3.36). The pooled objective response rate showed no overall difference, though regorafenib was inferior to nivolumab in subgroup analysis (odds ratio = 0.34; 95%CI: 0.20-0.58). Disease control rate did not differ significantly. No publication bias was detected.
CONCLUSION
Regorafenib offers a survival advantage in advanced HCC but does not significantly improve tumor response rates compared to alternative therapies.
Core Tip: This study presents a comprehensive synthesis of current evidence regarding regorafenib’s clinical performance as a second-line treatment in patients with advanced hepatocellular carcinoma. Utilizing data from nine eligible studies, our meta-analysis provides an updated assessment of survival outcomes and tumor response metrics. Notably, regorafenib demonstrated a statistically significant improvement in overall survival compared to control groups, while objective tumor response rates did not show superiority, particularly when compared to immunotherapies such as nivolumab. Our results highlight regorafenib’s survival benefit and its role within a competitive therapeutic landscape.
