{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:23:33Z","timestamp":1790659413892,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004095","name":"Kyowa Kirin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004095","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>We aimed to confirm the efficacy and safety of the oral histone deacetylase inhibitor entinostat in Japanese patients with hormone receptor-positive advanced\/recurrent breast cancer and to explore potential biomarkers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This phase II, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov; NCT03291886) was conducted at 28 Japanese sites (September 2017\u2013July 2020; interim analysis cutoff: April 2019). Patients with progression\/relapse following non-steroidal aromatase inhibitors were randomized 1:1 to entinostat (5\u00a0mg\/week) or placebo, plus exemestane (25\u00a0mg\/day). Primary endpoint was progression-free survival; secondary endpoints included overall survival and safety. Exploratory biomarker outcomes included lysine acetylation, immune cell profiles, estrogen receptor 1 mutations and plasma chemokines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 133 randomized patients, 131 (65 entinostat, 66 placebo) who received study drug were analyzed. Median (95% confidence interval) progression-free survival was 5.8 (3.2\u20137.8) months for entinostat and 3.3 (3.1\u20135.8) months for placebo (hazard ratio [95% confidence interval]: 0.75 [0.50\u00a0\u2212\u00a01.14]; P\u00a0=\u00a00.189). Median overall survival was not reached in either group. Entinostat tended to prolong progression-free survival in patients aged \u226565\u00a0years, not endocrine resistant, or with estrogen receptor 1 Y537S mutation. Candidate biomarkers of efficacy (progression-free survival) included lysine acetylation in CD3+ cells, plasma interferon gamma-induced protein 10, dendritic cell CD86 expression, and CD4+ cell expression of human leukocyte antigen-DR and inducible T-cell co-stimulator. Safety was similar to non-Japanese populations; however, seven entinostat-treated patients (10.8%) had reversible lung injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In Japanese patients, the safety of entinostat plus exemestane was acceptable and progression-free survival was prolonged, although not significantly. Exploratory analyses identified potential biomarkers, including lysine acetylation, of efficacy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jjco\/hyac166","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T08:05:25Z","timestamp":1668758725000},"page":"4-15","source":"Crossref","is-referenced-by-count":16,"title":["Efficacy and exploratory biomarker analysis of entinostat plus exemestane in advanced or recurrent breast cancer: phase II randomized controlled trial"],"prefix":"10.1093","volume":"53","author":[{"given":"Hiroji","family":"Iwata","sequence":"first","affiliation":[{"name":"Aichi Cancer Center Hospital Department of Breast Oncology, , Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikiya","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Chiba Cancer Center Division of Breast Surgery, , Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norikazu","family":"Masuda","sequence":"additional","affiliation":[{"name":"Breast Oncology, National Hospital Organization, Osaka National Hospital Department of Surgery, , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6479-1660","authenticated-orcid":false,"given":"Toshinari","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Kanagawa Cancer Center Department of Breast and Endocrine Surgery, , Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Kumamoto University Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, , Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kokoro","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Cancer Institute Hospital of Japanese Foundation for Cancer Research Department of Breast Medical Oncology, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Tsurutani","sequence":"additional","affiliation":[{"name":"Showa University Advanced Cancer Translational Research Institute, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Iwasa","sequence":"additional","affiliation":[{"name":"Showa University Advanced Cancer Translational Research Institute, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Yonemori","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital Department of Medical Oncology, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Tamura","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital Department of Medical Oncology, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Aruga","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Department of Breast Surgery, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Tokunaga","sequence":"additional","affiliation":[{"name":"National Hospital Organization Kyushu Cancer Center Department of Breast Oncology, , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Niigata Cancer Center Hospital Department of Surgery, , Niigata, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health Developmental Therapeutics Branch, Center for Cancer Research, , Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yuno","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health Developmental Therapeutics Branch, Center for Cancer Research, , Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azusa","family":"Kawabata","sequence":"additional","affiliation":[{"name":"Kyowa Kirin Co., Ltd R&D Division, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Seike","sequence":"additional","affiliation":[{"name":"Kyowa Kirin Co., Ltd R&D Division, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Kaneda","sequence":"additional","affiliation":[{"name":"Kyowa Kirin Co., Ltd R&D Division, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yozo","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Kyowa Kirin 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