{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:43:24Z","timestamp":1791477804270,"version":"4.3.4"},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A previous randomized phase 2 study of hepatocellular carcinoma revealed that the c\u2010Met inhibitor tivantinib as second\u2010line treatment significantly prolonged progression\u2010free survival in a subpopulation whose tumor samples highly expressed c\u2010Met (MET\u2010high). Accordingly, this phase 3 study was conducted to evaluate the efficacy of tivantinib as a second\u2010line treatment for Japanese patients with MET\u2010high hepatocellular carcinoma. This randomized, double\u2010blind, placebo\u2010controlled study was conducted at 60 centers in Japan. Hepatocellular carcinoma patients with one prior sorafenib treatment and those with MET\u2010high tumor samples were eligible for inclusion. Registered patients were randomly assigned to either the tivantinib or placebo group at a 2:1 ratio and were treated with twice\u2010a\u2010day oral tivantinib (120\u00a0mg bid) or placebo until the discontinuation criteria were met. The primary endpoint was progression\u2010free survival while the secondary endpoints included overall survival and safety. Between January 2014 and June 2016, 386 patients provided consent, and 195 patients were randomized to the tivantinib (n\u00a0=\u00a0134) or placebo (n\u00a0=\u00a061) group. Median progression\u2010free survival was 2.8 (95% confidence interval: 2.7\u20102.9) and 2.3 (1.5\u20102.8) mo in the tivantinib and placebo groups, respectively (hazard ratio\u00a0=\u00a00.74, 95% confidence interval: 0.52\u20101.04,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a0.082). Median overall survival was 10.3 (95% confidence interval: 8.1\u201011.6) and 8.5 (6.2\u201011.4) mo in the tivantinib and placebo group, respectively (hazard ratio\u00a0=\u00a00.82, 95% confidence interval: 0.58\u20101.15). The most common tivantinib\u2010related grade\u00a0\u22653 adverse events were neutropenia (31.6%), leukocytopenia (24.8%), and anemia (12.0%). This study did not confirm the significant efficacy of tivantinib as a second\u2010line treatment for Japanese patients with MET\u2010high hepatocellular carcinoma. (NCT02029157).\n                  <\/jats:p>","DOI":"10.1111\/cas.14582","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T06:40:27Z","timestamp":1595832027000},"page":"3759-3769","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["A randomized, double\u2010blind, placebo\u2010controlled, phase 3 study of tivantinib in Japanese patients with MET\u2010high hepatocellular carcinoma"],"prefix":"10.1111","volume":"111","author":[{"given":"Masatoshi","family":"Kudo","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Faculty of Medicine Kindai University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Medical Oncology Kanagawa Cancer Center Kanagawa 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