lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

Chidamide Plus Exemestane for Postmenopausal Patients with Hormone-Receptor-Positive Advanced Breast Cancer (ACE Study): A Randomised, Double-Blind, Placebo-Controlled Phase 3 Trial

90 Pages Posted: 5 Feb 2019

See all articles by Zefei Jiang

Zefei Jiang

Chinese PLA General Hospital, Fifth Medical Centre

Wei Li

Jilin University (JLU) - First Affiliated Hospital

Xichun Hu

Fudan University - Shanghai Cancer Center (FUSCC)

Qingyuan Zhang

Harbin Medical University - Cancer Hospital

Tao Sun

Liaoning Cancer Hospital & Institute

Shude Cui

Henan Cancer Hospital

Shusen Wang

Sun Yat-Sen University (SYSU) - Cancer Center

Quchang Ouyang

Hunan Cancer Hospital

Yongmei Yin

Jiangsu Province People's Hospital

Cuizhi Geng

Tumour Hospital of Hebei Province

Zhongsheng Tong

Tianjin Medical University

Ying Cheng

Jilin Cancer Hospital

Yueyin Pan

Anhui Provincial Hospital

Yuping Sun

Shandong University - Jinan Central Hospital

Hong Wang

Third Hospital of Nanchang

Tao Ouyang

Beijing Cancer Hospital

Kangsheng Gu

Anhui Medical University - First Affiliated Hospital

Jifeng Feng

Jiangsu Cancer Hospital - Department of Medical Oncology; Nanjing Medical University - Jiangsu Institute of Cancer Research; Nanjing Medical University - Affiliated Cancer Hospital

Xiaojia Wang

Zhejiang Cancer Hospital

Shubin Wang

Peking University - Shenzhen Hospital

Tianshu Liu

Fudan University - Department of Medical Oncology; Fudan University - Center of Evidence-based Medicine

Jinghua Gao

Cangzhou Central Hospital

Massimo Cristofanilli

Northwestern University - Feinberg School of Medicine

Zhiqiang Ning

Chipscreen Biosciences Ltd

Xianping Lu

Chipscreen Biosciences Ltd

More...

Abstract

Background: Chidamide is an oral subtype-selective histone deacetylase (HDAC) inhibitor that demonstrated encouraging anti-tumour activity when combined with exemestane in hormone-receptor (HR)-positive advanced breast cancer patients. The current study aimed to assess the efficacy and safety of chidamide plus exemestane in postmenopausal patients with advanced, HR-positive breast cancer.

Methods: In this phase 3 trial, we compared chidamide and exemestane versus placebo and exemestane in 365 postmenopausal patients (randomised as a 2:1 ratio) with HR-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had relapsed or progressed after previous endocrine therapy. The primary end point was progression-free survival, as assessed by the investigators. Secondary end points included overall survival, objective response, clinical benefit rate, and safety.

Findings: The median progression-free survival on the basis of investigator assessment was 7·4 months (95% CI 5·5-9·2) in the chidamide group versus 3·8 months (95% CI 3·7-5·5) in the placebo group (HR 0·75, 95% CI 0·58-0·98; p=0.034). The median progression-free survival was 9.2 months and 3.8 months, respectively, according to central assessment (HR 0·71, 95% CI 0·53-0·96; p=0.024). Objective response rates were 18% and 9% (p=0·026), and clinical benefit rates were 47% and 36% (p=0·034) in the chidamide group and placebo group, respectively. The most common grade 3 or 4 adverse events in the chidamide group were neutropenia (51% vs. 3% in the placebo group), thrombocytopenia (27% vs. 3%), and leucopenia (19% vs. 3%). Serious adverse events occurred in 51 (21%) patients in the chidamide group and 7 (6%) patients in the placebo group. No treatment related death was reported.

Interpretation: This is the first phase 3 trial to demonstrate that a selective HDAC inhibitor plus endocrine blockade improves progression-free survival in patients with HR-positive advanced breast cancer progressing after prior endocrine therapy.

Trial Registration Number: This study is registered with ClinicalTrials.gov, number NCT02482753.

Funding: Chipscreen Biosciences

Declaration of Interest: ZN and XP are employees of Chipscreen Biosciences Ltd. The other authors declare no competing interests.

Ethical Approval: The Ethics Committee at each participating centre approved the study which was
conducted in accordance with the principles of Good Clinical Practice, the Declaration of Helsinki
and the regulations of China.

Keywords: Chidamide; Histone deacetylase inhibitor; Exemestane; Hormonereceptor- positive; Advanced breast cancer; Phase 3 trial

Suggested Citation

Jiang, Zefei and Li, Wei and Hu, Xichun and Zhang, Qingyuan and Sun, Tao and Cui, Shude and Wang, Shusen and Ouyang, Quchang and Yin, Yongmei and Geng, Cuizhi and Tong, Zhongsheng and Cheng, Ying and Pan, Yueyin and Sun, Yuping and Wang, Hong and Ouyang, Tao and Gu, Kangsheng and Feng, Jifeng and Wang, Xiaojia and Wang, Shubin and Liu, Tianshu and Gao, Jinghua and Cristofanilli, Massimo and Ning, Zhiqiang and Lu, Xianping, Chidamide Plus Exemestane for Postmenopausal Patients with Hormone-Receptor-Positive Advanced Breast Cancer (ACE Study): A Randomised, Double-Blind, Placebo-Controlled Phase 3 Trial (January 31, 2019). Available at SSRN: https://ssrn.com/abstract=3327363

Zefei Jiang (Contact Author)

Chinese PLA General Hospital, Fifth Medical Centre ( email )

Beijing
China

Wei Li

Jilin University (JLU) - First Affiliated Hospital

71 Xinmin Street
Changchun, Jilin 130021
China

Xichun Hu

Fudan University - Shanghai Cancer Center (FUSCC)

Shanghai, 200032
China

Qingyuan Zhang

Harbin Medical University - Cancer Hospital

China

Tao Sun

Liaoning Cancer Hospital & Institute

Shenyang
China

Shude Cui

Henan Cancer Hospital

Zhengzhou
China

Shusen Wang

Sun Yat-Sen University (SYSU) - Cancer Center

651 Dongfeng East Road
Guangzhou, 510060
China

Quchang Ouyang

Hunan Cancer Hospital

Changsha, 410013
China

Yongmei Yin

Jiangsu Province People's Hospital

Nanjing
China

Cuizhi Geng

Tumour Hospital of Hebei Province

Shijiazhuang
China

Zhongsheng Tong

Tianjin Medical University

Tianjin Shi
China

Ying Cheng

Jilin Cancer Hospital

Changchun
China

Yueyin Pan

Anhui Provincial Hospital

Hefei
China

Yuping Sun

Shandong University - Jinan Central Hospital

No. 105, Jiefang Road
Jinan, Shandong 250013
China

Hong Wang

Third Hospital of Nanchang

Nanchang
China

Tao Ouyang

Beijing Cancer Hospital

Beijing
China

Kangsheng Gu

Anhui Medical University - First Affiliated Hospital

Meishan Road 81
Hefei, Anhui 230032
China

Jifeng Feng

Jiangsu Cancer Hospital - Department of Medical Oncology ( email )

Nanjing
China

Nanjing Medical University - Jiangsu Institute of Cancer Research ( email )

Nanjing
China

Nanjing Medical University - Affiliated Cancer Hospital ( email )

Nanjing
China

Xiaojia Wang

Zhejiang Cancer Hospital

China

Shubin Wang

Peking University - Shenzhen Hospital

Shenzhen, 518000
China

Tianshu Liu

Fudan University - Department of Medical Oncology ( email )

China

Fudan University - Center of Evidence-based Medicine ( email )

Shanghai
China

Jinghua Gao

Cangzhou Central Hospital

Cangzhou
China

Massimo Cristofanilli

Northwestern University - Feinberg School of Medicine

Chicago, IL 60611
United States

Zhiqiang Ning

Chipscreen Biosciences Ltd

Shenzhen
China

Xianping Lu

Chipscreen Biosciences Ltd

Shenzhen
China

Click here to go to TheLancet.com

Go to TheLancet.com

Paper statistics

Abstract Views
78
Downloads
14