{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:12:15Z","timestamp":1790460735988,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20fk0210067h0001"],"award-info":[{"award-number":["JP20fk0210067h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The present study aimed to clarify the efficacy and safety of ramucirumab in a real-world setting, including patients who experienced two or more systemic treatments or whose hepatic reserve was deteriorated. Methods: In total, 79 patients with hepatocellular carcinoma (HCC) from 14 institutes throughout Japan were retrospectively analyzed. The response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and AEs were recorded according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Results: Median overall survival (OS) in the total cohort was 7.5 months (m). Median OS was 8.8 m in patients who were administered ramucirumab as a second-line treatment, while it was 7.3 m in third- or later-line treatment. Progression-free survival rates in the second- and third- or later-line therapies were 3.2 m and 3.2 m, respectively. The disease control rate (DCR) in the study was 43%. There were no statistically significant differences in DCR between the treatment courses. Regarding adverse events (AEs), the development of ascites was observed significantly more frequently in modified albumin\u2013bilirubin (mALBI) 2b\/3 patients than in mALBI 1\/2a patients (54.5% vs. 25.0%, p = 0.03). Conclusions: Ramucirumab is useful as a second-line therapy and feasible as a third- or later-line treatment for HCC.<\/jats:p>","DOI":"10.3390\/cancers14122975","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T01:48:12Z","timestamp":1655430492000},"page":"2975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Real-World Data on Ramucirumab Therapy including Patients Who Experienced Two or More Systemic Treatments: A Multicenter Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6117-4990","authenticated-orcid":false,"given":"Yutaka","family":"Yasui","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-8931","authenticated-orcid":false,"given":"Masayuki","family":"Kurosaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0436-5915","authenticated-orcid":false,"given":"Kaoru","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitomi","family":"Hasebe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa 070-8530, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa 070-8530, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4534-6692","authenticated-orcid":false,"given":"Chikara","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Takamatsu Red Cross Hospital, Takamatsu 760-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji","family":"Joko","sequence":"additional","affiliation":[{"name":"Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Ochi","sequence":"additional","affiliation":[{"name":"Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji 670-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji 670-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Furuta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Masuda Red Cross Hospital, Masuda 698-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto 605-0981, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima 730-8619, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Japanese Red Cross Ise Hospital, Ise 516-8512, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Akahane","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Ishinomaki Red Cross Hospital, Ishinomaki 986-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Tamada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Takatsuki Red Cross Hospital, Takatsuki 569-1096, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Matsue Red Cross Hospital, Matsue 690-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Otsu Red Cross Hospital, Otsu 520-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akeri","family":"Mitsuda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Japanese Red Cross Tottori Hospital, Tottori 680-8517, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namiki","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jhep.2019.09.010","article-title":"Molecular therapies for HCC: Looking outside the box","volume":"72","author":"Faivre","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1111\/liv.14533","article-title":"Navigating the new landscape of second-line treatment in advanced hepatocellular carcinoma","volume":"40","author":"Rimassa","year":"2020","journal-title":"Liver Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S1470-2045(15)00050-9","article-title":"Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): A randomised, double-blind, multicentre, phase 3 trial","volume":"16","author":"Zhu","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S1470-2045(18)30937-9","article-title":"Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"20","author":"Zhu","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e204930","DOI":"10.1001\/jamaoncol.2020.4930","article-title":"Systemic Therapy and Sequencing Options in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-analysis","volume":"6","author":"Sonbol","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. 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Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1159\/000507022","article-title":"Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma","volume":"9","author":"Maruta","year":"2020","journal-title":"Liver Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/hepr.13511","article-title":"Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria","volume":"50","author":"Sho","year":"2020","journal-title":"Hepatol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tsuchiya, K., Kurosaki, M., Sakamoto, A., Marusawa, H., Kojima, Y., Hasebe, C., Arai, H., Joko, K., Kondo, M., and Tsuji, K. (2021). The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study. 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Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/12\/2975\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:33:30Z","timestamp":1760139210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/12\/2975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,16]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["cancers14122975"],"URL":"https:\/\/doi.org\/10.3390\/cancers14122975","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,16]]}}}