Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double- blind, placebo-controlled, phase 3 trial

作者：Xu, Binghe^*; Zhang, Qingyuan; Hu, Xichun; Li, Qing; Sun, Tao; Li, Wei; Ouyang, Quchang; Wang, Jingfen; Tong, Zhongsheng; Yan, Min; Li, Huiping; Zeng, Xiaohua; Shan, Changping; Wang, Xian; Yan, Xi; Zhang, Jian; Zhang, Yue; Wang, Jiani; Zhang, Liang; Lin, Ying; Feng, Jifeng; Chen, Qianjun; Huang, Jian; Zhang, Lu; Yang, Lisong; Tian, Ying; Shang, Hongyan

来源：Acta Pharmaceutica Sinica B, 2023, 13(5): 2250-2258.

DOI：10.1016/j.apsb.2023.02.001

• Advanced breast cancer
• Hormone receptor-positive
• Histone deacetylase inhibitors
• Phase 3 clinical trial

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after >1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade >3 adverse events (AEs) occurred in 154 (65.5%) pa-tients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade >3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).(c) 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

• 单位
  中国医学科学院北京协和医院; 中山大学; 浙江大学; 重庆大学; 复旦大学; 哈尔滨医科大学; 吉林大学; 郑州大学; 四川大学