Efficacy and safety of entinostat plus exemestane in hormone receptor-positive breast cancer: a systematic review meta-analysis of randomized controlled trials

Giaquinto AN, Sung H, Miller KD, Kramer JL, Newman LA, Minihan A et al (2022) Breast cancer statistics, 2022. CA Cancer J Clin 72:524–541

Article  PubMed  Google Scholar 

Siegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. CA Cancer J Clin 74:12–49

Article  PubMed  Google Scholar 

Huang H, Wei T, Zhang A, Zhang H, Kong L, Li Y et al (2024) Trends in the incidence and survival of women with hormone receptor-positive breast cancer from 1990 to 2019: a large population-based analysis. Sci Rep 14:1–12

Google Scholar 

Clark GM, Osborne CK, McGuire WL (1984) Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. J Clin Oncol 2:1102–1109. https://doi.org/10.1200/JCO.1984.2.10.1102

Article  CAS  PubMed  Google Scholar 

Zhang MH, Man HT, Zhao XD, Dong N, Ma SL (2014) Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review). Biomed Rep 2:41–52

Article  PubMed  Google Scholar 

Cao LQ, Sun H, Xie Y, Patel H, Bo L, Lin H et al (2024) Therapeutic evolution in HR+/HER2- breast cancer: from targeted therapy to endocrine therapy. Front Pharmacol 15:1340764

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cardoso F, Paluch-Shimon S, Senkus E, Curigliano G, Aapro MS, André F et al (2020) 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol 31:1623–1649

Article  CAS  PubMed  Google Scholar 

Keskinkilic M, Arayici ME, Basbinar Y, Ellidokuz H, Yavuzsen T, Oztop I (2024) The efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in the adjuvant treatment of patients with high-risk invasive HR+/HER2-early breast cancer: A comprehensive updated meta-analysis of randomized clinical trials. Breast 78:103815

Article  PubMed  PubMed Central  Google Scholar 

Mittal A, Molto Valiente C, Tamimi F, Schlam I, Sammons S, Tolaney SM et al (2023) Filling the Gap after CDK4/6 Inhibitors: Novel Endocrine and Biologic Treatment Options for Metastatic Hormone Receptor Positive Breast Cancer. Cancers 15:2015

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gennari A, André F, Barrios CH, Cortés J, de Azambuja E, DeMichele A et al (2021) ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer ☆. Ann Oncol 32:1475–1495

Article  CAS  PubMed  Google Scholar 

Gradishar WJ, Moran MS, Abraham J, Abramson V, Aft R, Agnese D et al (2023) NCCN Guidelines® Insights: Breast Cancer, Version 4.2023. J Natl Compr Canc Netw 21:594–608

Article  PubMed  Google Scholar 

Sobral AF, Amaral C, Correia-da-Silva G, Teixeira N (2016) Unravelling exemestane: From biology to clinical prospects. J Steroid Biochem Mol Biol 163:1–11

Article  CAS  PubMed  Google Scholar 

Brufsky AM, Dickler MN (2018) Estrogen receptor-positive breast cancer: exploiting signaling pathways implicated in endocrine resistance. Oncologist 23:528–539

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hanamura T, Hayashi S (2018) Overcoming aromatase inhibitor resistance in breast cancer: possible mechanisms and clinical applications. Breast Cancer 25:379–391

Article  PubMed  Google Scholar 

Connolly RM, Rudek MA, Piekarz R (2017) Entinostat: a promising treatment option for patients with advanced breast cancer. Future Oncol 13:1137–1148. https://doi.org/10.2217/fon-2016-0526

Article  CAS  PubMed  PubMed Central  Google Scholar 

Connolly RM, Zhao F, Miller KD, Lee MJ, Piekarz RL, Smith KL et al (2021) Randomized phase III trial of endocrine therapy plus entinostat or placebo in hormone receptor-positive advanced breast cancer a trial of the ECOG-ACRIN Cancer Research Group. J Clin Oncol 39:3171–81

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu B, Zhang Q, Hu X, Li Q, Sun T, Li W et al (2023) 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. Acta Pharm Sin B 13:2250–2258

Article  CAS  PubMed  PubMed Central  Google Scholar 

Iwata H, Nakamura R, Masuda N, Yamashita T, Yamamoto Y, Kobayashi K et al (2023) Efficacy and exploratory biomarker analysis of entinostat plus exemestane in advanced or recurrent breast cancer: phase II randomized controlled trial. Jpn J Clin Oncol 53:4–15

Article  PubMed  Google Scholar 

Yardley DA, Ismail-Khan RR, Melichar B, Lichinitser M, Munster PN, Klein PM et al (2013) Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J Clin Oncol 31:2128–2135

Article  CAS  PubMed  PubMed Central  Google Scholar 

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71

Article  PubMed  PubMed Central  Google Scholar 

Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ et al (2019) Cochrane handbook for systematic reviews of interventions. Wiley, Hoboken

Book  Google Scholar 

Buglio D, Khaskhely NM, Voo KS, Martinez-Valdez H, Liu YJ, Younes A (2011) HDAC11 plays an essential role in regulating OX40 ligand expression in Hodgkin lymphoma. Blood 117:2910–2917

Article  CAS  PubMed  PubMed Central  Google Scholar 

Condorelli F, Gnemmi I, Vallario A, Genazzani AA, Canonico PL (2008) Inhibitors of histone deacetylase (HDAC) restore the p53 pathway in neuroblastoma cells. Br J Pharmacol 153:657–668

Article  CAS  PubMed  Google Scholar 

Witta SE, Gemmill RM, Hirsch FR, Coldren CD, Hedman K, Ravdel L et al (2006) Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 66:944–950

Article  CAS  PubMed  Google Scholar 

Sabnis GJ, Goloubeva OG, Kazi AA, Shah P, Brodie AH (2013) HDAC inhibitor entinostat restores responsiveness of letrozole-resistant MCF-7Ca xenografts to aromatase inhibitors through modulation of Her-2. Mol Cancer Ther 12:2804–2816

Article  CAS  PubMed  Google Scholar 

The ASCO Post [Internet]. [cited 2025 Feb 12]. Available from: https://ascopost.com/News/8525

Masuda N, Tamura K, Yasojima H, Shimomura A, Sawaki M, Lee MJ et al (2021) Phase 1 trial of entinostat as monotherapy and combined with exemestane in Japanese patients with hormone receptor-positive advanced breast cancer. BMC Cancer 21:1–12. https://doi.org/10.1186/s12885-021-08973-4

Article  CAS  Google Scholar 

Wang J, Zhang Q, Li Q, Mu Y, Jing J, Li H et al (2021) Phase I study and pilot efficacy analysis of entinostat, a novel histone deacetylase inhibitor, in Chinese postmenopausal women with hormone receptor-positive metastatic breast cancer. Target Oncol 16:591–599

Article  PubMed  PubMed Central  Google Scholar 

Yardley DA (2010) Visceral disease in patients with metastatic breast cancer: efficacy and safety of treatment with ixabepilone and other chemotherapeutic agents. Clin Breast Cancer 10:64–73

Article  CAS  PubMed  Google Scholar 

Wang C, Lin Y, Zhu H, Zhou Y, Mao F, Huang X et al (2022) Efficacy and safety profile of histone deacetylase inhibitors for metastatic breast cancer: a meta-analysis. Front Oncol 12:901152

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang Z, Li W, Hu X, Zhang Q, Sun T, Cui S et al (2019) Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20:806–815

Article  CAS 

Comments (0)

No login
gif