{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T12:15:27Z","timestamp":1769170527057,"version":"3.49.0"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The REACH and REACH\u20102 trials investigated ramucirumab versus placebo in patients with advanced hepatocellular carcinoma (HCC). Ascites is common in HCC and is associated with poorer outcomes. This exploratory, pooled meta\u2010analysis of patients with baseline <jats:italic>\u03b1<\/jats:italic>\u2010fetoprotein (AFP) \u2265400\u00a0ng\/ml investigated outcomes by treatment\u2010emergent (TE) ascites in REACH and REACH\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A pooled meta\u2010analysis of independent patient data for participants (<jats:italic>N<\/jats:italic>\u00a0=\u00a0542) with baseline AFP \u2265400\u00a0ng\/ml (stratified by study) from REACH and REACH\u20102 was carried out. Overall survival (OS) and progression\u2010free survival (PFS) were evaluated by Kaplan\u2013Meier estimator, and OS further assessed by Cox models. The effect of TE ascites on OS was evaluated by multivariate Cox models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment\u2010emergent ascites developed in 66 patients (20.9%) in the ramucirumab group and 33 patients (14.8%) in the placebo group. When adjusted for treatment duration, the incidence rates per 100 patient\u2010years of any grade TE ascites were 59.1 and 71.9 for the ramucirumab and placebo groups, respectively, and the incidence of grade \u22653\u00a0TE ascites were 13.4 and 19.6, respectively. Treatment\u2010emergent ascites was associated with TE hypoalbuminemia (odds ratio 4.9; 95% confidence interval 2.5\u20129.3), but not TE proteinuria or hypertension. One patient discontinued ramucirumab treatment due to TE ascites. Ramucirumab treatment improved OS and PFS compared with placebo, irrespective of TE ascites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>When adjusted for treatment duration, the incidence of TE ascites was no higher in patients who received ramucirumab than in those who received placebo. Ramucirumab was well tolerated and provided a survival benefit irrespective of the development of TE ascites.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13638","type":"journal-article","created":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T16:56:17Z","timestamp":1616259377000},"page":"715-721","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ramucirumab in patients with advanced hepatocellular carcinoma and elevated <i>\u03b1<\/i>\u2010fetoprotein: Outcomes by treatment\u2010emergent ascites"],"prefix":"10.1111","volume":"51","author":[{"given":"Masatoshi","family":"Kudo","sequence":"first","affiliation":[{"name":"Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East  Kashiwa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R.","family":"Galle","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik Universit\u00e4tsmedizin  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Kanazawa University Hospital  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard S.","family":"Finn","sequence":"additional","affiliation":[{"name":"University of California Los Angeles Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Liang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachi","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Abada","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan C.","family":"Widau","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew X.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center  Boston Massachusetts USA"},{"name":"Jiahui International Cancer Center, Jiahui Health  Shanghai 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