{"doi":"10.1093/jjco/hyac166","title":"Efficacy and exploratory biomarker analysis of entinostat plus exemestane in advanced or recurrent breast cancer: phase II randomized controlled trial","abstract":"BACKGROUND: 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. METHODS: This phase II, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov; NCT03291886) was conducted at 28 Japanese sites (September 2017-July 2020; interim analysis cutoff: April 2019). Patients with progression/relapse following non-steroidal aromatase inhibitors were randomized 1:1 to entinostat (5 mg/week) or placebo, plus exemestane (25 mg/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. RESULTS: 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 (3.2-7.8) months for entinostat and 3.3 (3.1-5.8) months for placebo (hazard ratio [95% confidence interval]: 0.75 [0.50 - 1.14]; P = 0.189). Median overall survival was not reached in either group. Entinostat tended to prolong progression-free survival in patients aged ≥65 years, 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. CONCLUSIONS: 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.","journal":"Japanese Journal of Clinical Oncology","year":2022,"id":261545,"datarank":0.7003495567129707,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.2844612483770035,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.2844612483770035,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":15,"citers_with_citation_signal":13,"citers_with_endowment":13,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9416,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03291886"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":916390,"name":"Rikiya Nakamura","orcid":"0000-0002-4349-9046","position":1,"is_corresponding":false},{"id":916391,"name":"Norikazu Masuda","orcid":"0000-0002-7302-0278","position":2,"is_corresponding":false},{"id":916392,"name":"Toshinari Yamashita","orcid":"0000-0002-6479-1660","position":3,"is_corresponding":false},{"id":916393,"name":"Yutaka Yamamoto","orcid":"0000-0001-6147-6828","position":4,"is_corresponding":false},{"id":916394,"name":"Kokoro Kobayashi","orcid":"0000-0001-6639-0468","position":5,"is_corresponding":false},{"id":231711,"name":"Junji Tsurutani","orcid":"0000-0002-6260-6943","position":6,"is_corresponding":false},{"id":916395,"name":"Tsutomu Iwasa","orcid":"0000-0001-5996-0602","position":7,"is_corresponding":false},{"id":916396,"name":"Kan Yonemori","orcid":"0000-0002-7624-7611","position":8,"is_corresponding":false},{"id":916397,"name":"Kenji Tamura","orcid":"0000-0003-0318-5162","position":9,"is_corresponding":false},{"id":916398,"name":"Tomoyuki Aruga","orcid":"0000-0003-3442-8972","position":10,"is_corresponding":false},{"id":916399,"name":"Eriko Tokunaga","orcid":"0000-0002-1640-5315","position":11,"is_corresponding":false},{"id":916872,"name":"Koji Kaneko","orcid":null,"position":12,"is_corresponding":false},{"id":268299,"name":"Min-Jung Lee","orcid":"0000-0003-3943-8133","position":13,"is_corresponding":false},{"id":269526,"name":"Akira Yuno","orcid":null,"position":14,"is_corresponding":false},{"id":916873,"name":"Azusa Kawabata","orcid":null,"position":15,"is_corresponding":false},{"id":916874,"name":"Toshihiro Seike","orcid":null,"position":16,"is_corresponding":false},{"id":916400,"name":"Ayumi Kaneda","orcid":"0009-0007-9788-682X","position":17,"is_corresponding":false},{"id":916875,"name":"Yozo Nishimura","orcid":null,"position":18,"is_corresponding":false},{"id":232026,"name":"Jane B. Trepel","orcid":"0000-0002-7681-6554","position":19,"is_corresponding":false},{"id":916401,"name":"Shigehira Saji","orcid":"0000-0002-6732-8030","position":20,"is_corresponding":false},{"id":231712,"name":"Hiroji Iwata","orcid":"0000-0002-0242-4718","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T00:26:16.663144Z","pmid":"36398439","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}