PMID- 34196874
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220531
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Print)
IS  - 1776-2596 (Linking)
VI  - 16
IP  - 5
DP  - 2021 Sep
TI  - Phase I Study and Pilot Efficacy Analysis of Entinostat, a Novel Histone 
      Deacetylase Inhibitor, in Chinese Postmenopausal Women with Hormone 
      Receptor-Positive Metastatic Breast Cancer.
PG  - 591-599
LID - 10.1007/s11523-021-00823-4 [doi]
AB  - BACKGROUND: Previous clinical trials have demonstrated that entinostat in 
      combination with exemestane had good tolerability and significant clinical 
      efficacy in patients with advanced hormone receptor positive (HR+) and HER2 
      negative (HER2-) metastatic breast cancer (MBC) in the USA. However, no clinical 
      trials have been conducted in Chinese populations. OBJECTIVE: To investigate the 
      safety, pharmacokinetics, and pilot efficacy of entinostat with or without 
      exemestane in Chinese postmenopausal patients with locally advanced or metastatic 
      HR+ /HER2- MBC. PATIENTS AND METHODS: Nineteen patients received entinostat for 4 
      weeks (dose-limiting toxicity (DLT) observation stage) at 3, 5, or 7 mg/week, 
      with a "3+3" dose-escalation design and in combination with exemestane thereafter 
      (extended treatment stage: entinostat, 3 or 5 mg/week; exemestane, 25 mg/day). An 
      additional 21 patients were enrolled to assess the entinostat (5 mg) plus 
      exemestane (25 mg) pharmacokinetic profile and potential efficacy. RESULTS: The 
      peak entinostat serum concentration and area under the curve increased dose 
      proportionally, without significant interaction between entinostat and 
      exemestane. Entinostat was well tolerated at all doses. The most common grade 3/4 
      adverse effects (AEs) included neutropenia (31.6%) and thrombocytopenia (15.8%). 
      In the DLT observation stage, grade 3/4 AEs accounted for 16.7% in the 5 mg group 
      with one suspicious DLT (G3 ventricular tachycardia) and 33.3% in the 7 mg group. 
      In the extended treatment stage, 2/16 patients achieved partial response and 
      three patients experienced stable disease (> 12 weeks). The median 
      progression-free survival was 9.41 months for the additional 21 patients, who 
      experienced grade 3/4 AEs of neutropenia (38%), thrombocytopenia (9.5%), anemia 
      (9.5%), and fatigue (9.5%). CONCLUSION: Entinostat with exemestane showed 
      reasonable safety, tolerability, and encouraging efficacy in Chinese patients 
      with HR+/HER2- MBC. These results support further evaluation in a randomized, 
      double-blind Phase III study with a weekly 5 mg entinostat dose in a Chinese 
      population. TRIAL REGISTRATION: NCT02833155.
CI  - (c) 2021. The Author(s).
FAU - Wang, Jiani
AU  - Wang J
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, Beijing, 
      100021, China.
FAU - Zhang, Qingyuan
AU  - Zhang Q
AD  - Department of Medical Oncology, Harbin Medical University Cancer Hospital, 
      Harbin, 150081, Heilongjiang, China.
FAU - Li, Qiao
AU  - Li Q
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, Beijing, 
      100021, China.
FAU - Mu, Yuxin
AU  - Mu Y
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, Beijing, 
      100021, China.
FAU - Jing, Jing
AU  - Jing J
AD  - Department of Thyroid and Breast Surgery, West China Hospital, Sichuan 
      University, Chengdu, 610041, Sichuan, China.
FAU - Li, Huiping
AU  - Li H
AD  - Department of Breast Oncology, Peking University Cancer Hospital and Institute, 
      No. 52, Beijing, 100142, China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Medical Oncology, The First Bethune Hospital of Jilin University, 
      Changchun, 130021, Jilin, China.
FAU - Wang, Jingfen
AU  - Wang J
AD  - Oncology Division of Breast Cancer, Linyi Cancer Hospital, Linyi, 276000, 
      Shandong, China.
FAU - Yu, Guohua
AU  - Yu G
AD  - Department of Breast Oncology, Weifang People's Hospital, Weifang, 261000, 
      Shandong, China.
FAU - Wang, Xian
AU  - Wang X
AD  - Department of Breast Oncology, Sir Run Run Shaw Hospital, Zhejiang University 
      School of Medicine, Hangzhou, 310016, Zhejiang, China.
FAU - Ouyang, Quchang
AU  - Ouyang Q
AD  - Oncology Division of Breast Cancer, Hunan Cancer Hospital, The Affiliated Cancer 
      Hospital of Xiangya School of Medicine, Central South University, Changsha, 
      410013, Hunan, China.
FAU - Hao, Jing
AU  - Hao J
AD  - Taizhou EOC Pharma Co., Ltd., Taizhou, 225300, Jiangsu, China.
FAU - Lu, Liang
AU  - Lu L
AD  - Taizhou EOC Pharma Co., Ltd., Taizhou, 225300, Jiangsu, China.
FAU - Zhou, Li
AU  - Zhou L
AD  - Taizhou EOC Pharma Co., Ltd., Taizhou, 225300, Jiangsu, China.
FAU - Guan, Jin
AU  - Guan J
AD  - Taizhou EOC Pharma Co., Ltd., Taizhou, 225300, Jiangsu, China.
FAU - Li, Qing
AU  - Li Q
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, Beijing, 
      100021, China. cheryliqing@126.com.
FAU - Xu, Binghe
AU  - Xu B
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, Beijing, 
      100021, China. xubinghe@medmail.com.
AD  - State Key Laboratory of Molecular Oncology, National Cancer Center/National 
      Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College, Beijing, 100021, China. 
      xubinghe@medmail.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT02833155
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210701
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Benzamides)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Pyridines)
RN  - 1ZNY4FKK9H (entinostat)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Benzamides/adverse effects
MH  - *Breast Neoplasms/drug therapy
MH  - China
MH  - Female
MH  - *Histone Deacetylase Inhibitors/adverse effects
MH  - Humans
MH  - Pilot Projects
MH  - Postmenopause
MH  - Pyridines/adverse effects
MH  - Treatment Outcome
PMC - PMC8484140
COIS- Jiani Wang, Qingyuan Zhang, Qiao Li, Yuxin Mu, Jing Jing, Huiping Li, Wei Li, 
      Jingfen Wang, Guohua Yu, Xian Wang, Quchang Ouyang, Jing Hao, Liang Lu, Li Zhou, 
      Jin Guan, Qing Li, and Binghe Xu declare that they have no conflicts of interest 
      that might be relevant to the contents of this article.
EDAT- 2021/07/02 06:00
MHDA- 2022/01/14 06:00
PMCR- 2021/07/01
CRDT- 2021/07/01 12:26
PHST- 2021/06/07 00:00 [accepted]
PHST- 2021/07/02 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2021/07/01 12:26 [entrez]
PHST- 2021/07/01 00:00 [pmc-release]
AID - 10.1007/s11523-021-00823-4 [pii]
AID - 823 [pii]
AID - 10.1007/s11523-021-00823-4 [doi]
PST - ppublish
SO  - Target Oncol. 2021 Sep;16(5):591-599. doi: 10.1007/s11523-021-00823-4. Epub 2021 
      Jul 1.