Fukushima M, Nakao Y, Sasaki R, Haraguchi M, Miuma S, Miyaaki H. Dramatic response to fourth-line ramucirumab after atezolizumab plus bevacizumab failure in advanced hepatocellular carcinoma: A case report. World J Clin Cases 2026; 14(15): 119781 [DOI: 10.12998/wjcc.v14.i15.119781]
Corresponding Author of This Article
Masanori Fukushima, MD, PhD, Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 8528501, Japan. ma-fukushima@nagasaki-u.ac.jp
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Report
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May 26, 2026 (publication date) through May 12, 2026
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Journal Information of This Article
Publication Name
World Journal of Clinical Cases
ISSN
2307-8960
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Fukushima M, Nakao Y, Sasaki R, Haraguchi M, Miuma S, Miyaaki H. Dramatic response to fourth-line ramucirumab after atezolizumab plus bevacizumab failure in advanced hepatocellular carcinoma: A case report. World J Clin Cases 2026; 14(15): 119781 [DOI: 10.12998/wjcc.v14.i15.119781]
Masanori Fukushima, Yasuhiko Nakao, Ryu Sasaki, Masafumi Haraguchi, Satoshi Miuma, Hisamitsu Miyaaki, Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 8528501, Japan
Author contributions: Fukushima M designed the report and determined the clinical significance of the case; Fukushima M, Nakao Y, Sasaki R, Haraguchi M, and Miuma S collected and analyzed the clinical and imaging data; Fukushima M analyzed the data and wrote the manuscript; Fukushima M treated the patient in this case; Miuma S and Miyaaki H supervised the clinical interpretation and manuscript development; all authors have read and approved the final manuscript.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Corresponding author: Masanori Fukushima, MD, PhD, Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 8528501, Japan. ma-fukushima@nagasaki-u.ac.jp
Received: February 24, 2026 Revised: March 13, 2026 Accepted: April 8, 2026 Published online: May 26, 2026 Processing time: 85 Days and 1 Hours
Abstract
BACKGROUND
Systemic treatment options for hepatocellular carcinoma (HCC) following atezolizumab plus bevacizumab (Atez/Bev) failure are limited, particularly for patients with deteriorated liver function and poor tolerance to tyrosine kinase inhibitors (TKIs). This case highlights the potential role of ramucirumab (RAM) as later-line therapy in challenging clinical settings.
CASE SUMMARY
An 83-year-old man with a history of hepatitis C-related HCC developed disseminated recurrence involving the splenic hilum 12 years after curative resection. The lesion was surgically resected following four courses of Atez/Bev. After 17 months, intrahepatic and liver surface recurrences were detected. Atez/Bev was reintroduced as a first-line therapy but resulted in disease progression after 17 courses. Second-line lenvatinib and third-line sorafenib were discontinued because of severe fatigue, appetite loss, marked tumor progression, and worsening liver function (Child-Pugh B). Given the patient’s elevated alpha-fetoprotein (AFP) level and intolerance to TKIs, RAM was initiated as fourth-line therapy. Tumor marker levels rapidly normalized, and imaging demonstrated a partial response. Liver function also improved, and the response was maintained for over 1 year with manageable toxicity.
CONCLUSION
Following Atez/Bev failure, RAM may provide mechanistically rational and effective therapy in AFP-high HCC for patients intolerant to kinase inhibitor.
Core Tip: Hepatocellular carcinoma with elevated alpha-fetoprotein levels that progresses after treatment with atezolizumab plus bevacizumab may involve enhanced vascular endothelial growth factor receptor-2 signaling, making ramucirumab a potentially effective treatment option.
