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.
机构：[1]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/CancerHospital, Chinese Academy of Medical Sciences and PekingUnion Medical College, No. 17, Panjiayuannanli, ChaoyangDistrict, Beijing 100021, China[2]State Key Laboratory of Molecular Oncology, NationalCancer Center/National Clinical Research Centerfor Cancer/Cancer Hospital, Chinese Academy of MedicalSciences and Peking Union Medical College, Beijing 100021,China[3]Department of Medical Oncology, Harbin MedicalUniversity Cancer Hospital, Harbin 150081, Heilongjiang,China[4]Department of Thyroid and Breast Surgery, West ChinaHospital, Sichuan University, Chengdu 610041, Sichuan,China[5]Department of Breast Oncology, Peking University CancerHospital and Institute, No. 52, Beijing 100142, China[6]Department of Medical Oncology, The First BethuneHospital of Jilin University, Changchun 130021, Jilin, China[7]Oncology Division of Breast Cancer, Linyi Cancer Hospital,Linyi 276000, Shandong, China[8]Department of Breast Oncology, Weifang People’s Hospital,Weifang 261000, Shandong, China[9]Department of Breast Oncology, Sir Run Run Shaw Hospital,Zhejiang University School of Medicine, Hangzhou 310016,Zhejiang, China[10]Oncology Division of Breast Cancer, Hunan CancerHospital, The Affiliated Cancer Hospital of Xiangya Schoolof Medicine, Central South University, Changsha 410013,Hunan, China[11]Taizhou EOC Pharma Co., Ltd., Taizhou 225300, Jiangsu,China
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.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.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.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%).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.NCT02833155.
基金：
This work was supported by the National Key Research and
Development Program of China (No. 2018YFC1312101) and Chinese
Academy of Medical Science Initiative for Innovative Medicine (No.
CAMS-2016-I2M-1-010).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|3 区医学
小类|4 区肿瘤学
最新[2023]版：
大类|3 区医学
小类|3 区肿瘤学
第一作者：
第一作者机构：[1]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/CancerHospital, Chinese Academy of Medical Sciences and PekingUnion Medical College, No. 17, Panjiayuannanli, ChaoyangDistrict, Beijing 100021, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/CancerHospital, Chinese Academy of Medical Sciences and PekingUnion Medical College, No. 17, Panjiayuannanli, ChaoyangDistrict, Beijing 100021, China[2]State Key Laboratory of Molecular Oncology, NationalCancer Center/National Clinical Research Centerfor Cancer/Cancer Hospital, Chinese Academy of MedicalSciences and Peking Union Medical College, Beijing 100021,China
推荐引用方式(GB/T 7714)：
Wang Jiani,Zhang Qingyuan,Li Qiao,et al.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.[J].Targeted oncology.2021,16(5):591-599.doi:10.1007/s11523-021-00823-4.
APA：
Wang Jiani,Zhang Qingyuan,Li Qiao,Mu Yuxin,Jing Jing...&Xu Binghe.(2021).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..Targeted oncology,16,(5)
MLA：
Wang Jiani,et al."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.".Targeted oncology 16..5(2021):591-599
