Entinostat plus exemestane for hormone receptor-positive advanced breast cancer: long-term overall survival results from the EOC103A3101 randomized controlled trial.
16 affiliations
- 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- 2Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
- 3Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
- 4Department of Galactophore, Liaoning Cancer Hospital & Institute, Shenyang, China.
- 5Department of Oncology, The First Hospital of Jilin University, Changchun, China.
- 6Department of Galactophore, Hunan Cancer Hospital, Changsha, China.
- 7Department of Galactophore, Linyi Cancer Hospital, Linyi, China.
- 8Department of Breast Medical Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
- 9Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
- 10Department of Breast Oncology, Beijing Cancer Hospital, Beijing, China.
- 11Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
- 12Department of Breast and Thyroid Oncology, Affiliated Hospital of Jining Medical Universtiy, Jining, China.
- 13Department of Medical Oncology, Run Run Shaw Hospital, Affiliated Hospital of Zhejiang University, Hangzhou, China.
- 14Taizhou EOC Pharma Co. Ltd., Taizhou, China.
- 15Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [email protected].
- 16State Key Laboratory of Molecular Oncology and Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [email protected].
Abstract
The addition of entinostat, a histone deacetylase inhibitor, to exemestane has demonstrated improved progression-free survival (PFS) in hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) following endocrine therapy failure in the EOC103A3101 randomized trial (NCT03538171). This study reports long-term overall survival (OS) results. In this study, 354 patients with HR + /HER2- ABC that had recurred or progressed after endocrine therapy were randomized (2:1) to receive entinostat plus exemestane (n = 235) or placebo plus exemestane (n = 119). After a median follow-up of 31.8 months, the median OS was 38.6 months (95% confidence interval [CI]: 29.6-44.0) in the entinostat-exemestane group versus 29.2 months (95% CI: 22.5-41.6) in the placebo-exemestane group (hazard ratio [HR] 0.83, 95% CI: 0.62-1.10, P = 0.184). The entinostat-exemestane group demonstrated more pronounced OS benefits when adjusting subsequent antitumor therapies such as cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, or the combination of endocrine therapy, CDK4/6 inhibitors, and chemotherapy. The sensitivity analysis based on the per-protocol set showed more significant OS benefits. The median time to post-discontinuation chemotherapy and chemotherapy-free survival in the entinostat-exemestane group were 11.7 and 9.3 months, respectively, compared to 6.8 and 5.6 months in the placebo-exemestane group (both P < 0.05). Grade ≥3 treatment-emergent adverse events occurred in 65.5% of patients in the entinostat-exemestane group, without new safety signals observed. In conclusion, among patients with HR + /HER2- ABC after endocrine therapy failure, entinostat plus exemestane was associated with a numerically longer OS, with an acceptable safety profile.
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BibTeX
@article{wang2026entinostat,
title = {{Entinostat plus exemestane for hormone receptor-positive advanced breast cancer: long-term overall survival results from the EOC103A3101 randomized controlled trial.}},
author = {Jiani Wang and Qingyuan Zhang and Xichun Hu and Tao Sun and Wei Li and Quchang Ouyang and Jingfen Wang and Zhongsheng Tong and Min Yan and Huiping Li and Xiaohua Zeng and Changping Shan and Xian Wang and Jian Zhang and Yue Zhang and Liang Zhang and Hongyan Shang and Binghe Xu},
journal = {Signal transduction and targeted therapy},
year = {2026},
month = oct,
doi = {10.1038/s41392-026-02899-8},
url = {https://europepmc.org/article/MED/42897132},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Entinostat plus exemestane for hormone receptor-positive advanced breast cancer: long-term overall survival results from the EOC103A3101 randomized controlled trial.
AU - Jiani Wang
AU - Qingyuan Zhang
AU - Xichun Hu
AU - Tao Sun
AU - Wei Li
AU - Quchang Ouyang
AU - Jingfen Wang
AU - Zhongsheng Tong
AU - Min Yan
AU - Huiping Li
AU - Xiaohua Zeng
AU - Changping Shan
AU - Xian Wang
AU - Jian Zhang
AU - Yue Zhang
AU - Liang Zhang
AU - Hongyan Shang
AU - Binghe Xu
PY - 2026
DA - 2026/10/20
JO - Signal transduction and targeted therapy
DO - 10.1038/s41392-026-02899-8
UR - https://europepmc.org/article/MED/42897132
AB - The addition of entinostat, a histone deacetylase inhibitor, to exemestane has demonstrated improved progression-free survival (PFS) in hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) following endocrine therapy failure in the EOC103A3101 randomized trial (NCT03538171). This study reports long-term overall survival (OS) results. In this study, 354 patients with HR + /HER2- ABC that had recurred or progressed after endocrine therapy were randomized (2:1) to receive entinostat plus exemestane (n = 235) or placebo plus exemestane (n = 119). After a median follow-up of 31.8 months, the median OS was 38.6 months (95% confidence interval [CI]: 29.6-44.0) in the entinostat-exemestane group versus 29.2 months (95% CI: 22.5-41.6) in the placebo-exemestane group (hazard ratio [HR] 0.83, 95% CI: 0.62-1.10, P = 0.184). The entinostat-exemestane group demonstrated more pronounced OS benefits when adjusting subsequent antitumor therapies such as cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, or the combination of endocrine therapy, CDK4/6 inhibitors, and chemotherapy. The sensitivity analysis based on the per-protocol set showed more significant OS benefits. The median time to post-discontinuation chemotherapy and chemotherapy-free survival in the entinostat-exemestane group were 11.7 and 9.3 months, respectively, compared to 6.8 and 5.6 months in the placebo-exemestane group (both P < 0.05). Grade ≥3 treatment-emergent adverse events occurred in 65.5% of patients in the entinostat-exemestane group, without new safety signals observed. In conclusion, among patients with HR + /HER2- ABC after endocrine therapy failure, entinostat plus exemestane was associated with a numerically longer OS, with an acceptable safety profile.
SN - 2095-9907
SN - 2059-3635
ER -