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.

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

Return

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.

Author: Binghe XU ¹ ; Qingyuan ZHANG ² ; Xichun HU ³ ; Qing LI ¹ ; Tao SUN ⁴ ; Wei LI ⁵ ; Quchang OUYANG ⁶ ; Jingfen WANG ⁷ ; Zhongsheng TONG ⁸ ; Min YAN ⁹ ; Huiping LI ¹⁰ ; Xiaohua ZENG ¹¹ ; Changping SHAN ¹² ; Xian WANG ¹³ ; Xi YAN ¹⁴ ; Jian ZHANG ³ ; Yue ZHANG ² ; Jiani WANG ¹ ; Liang ZHANG ⁴ ; Ying LIN ¹⁵ ; Jifeng FENG ¹⁶ ; Qianjun CHEN ¹⁷ ; Jian HUANG ¹⁸ ; Lu ZHANG ¹⁹ ; Lisong YANG ¹⁹ ; Ying TIAN ¹⁹ ; Hongyan SHANG ¹⁹
Author Information

1. Department of Medical Oncology and State Key Laboratory of Molecular Oncology, National Cancer Cener/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
2. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150000, China.
3. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200000, China.
4. Department of Galactophore, Liaoning Cancer Hospital & Institute, Shenyang 110801, China.
5. Department of Oncology, the First Hospital of Jilin University, Changchun 130061, China.
6. Department of Galactophore, Hunan Cancer Hospital, Changsha 410000, China.
7. Department of Galactophore, Linyi Cancer Hospital, Linyi 276000, China.
8. Department of Breast Medical Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300000, China.
9. Department of Breast Disease, Henan Breast Cancer Center, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China.
10. Department of Breast Oncology, Beijing Cancer Hospital, Beijing 100000, China.
11. Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing 400000, China.
12. Department of Breast and Thyroid Oncology, Affiliated Hospital of Jining Medical University, Changchun 130021, China.
13. Department of Medical Oncology, Run Run Shaw Hospital, Affiliated Hospital of Zhejiang University, Hangzhou 310003, China.
14. Department of Head and Heck Oncology, West China Hospital, Sichuan University, Chengdu 610000, China.
15. Department of Thyroid & Breast Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China.
16. Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing 210000, China.
17. Department of Galactophore, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510000, China.
18. Department of Oncological Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
19. Taizhou EOC Pharma Co., Ltd., Taizhou 318000, China.
Publication Type:Clinical Trial
Keywords: Advanced breast cancer; Histone deacetylase inhibitors; Hormone receptor-positive; Phase 3 clinical trial
From: Acta Pharmaceutica Sinica B 2023;13(5):2250-2258
CountryChina
Language:English
Abstract: 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).