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

来源：Acta Pharmaceutica Sinica B, 2023, 13(05): 2250-2258.

• 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%) patients 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).

• 单位
  湖南省肿瘤医院; 分子肿瘤学国家重点实验室; 浙江大学; 复旦大学; 中山大学; 中国医学科学院北京协和医院; 北京协和医学院; 四川大学; 郑州大学; 天津医科大学