E2112: Randomized phase III trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer

Sri Lakshmi Hyndavi Yeruva, Fengmin Zhao, Kathy Miller, Amye J. Tevaarwerk, Lynne I. Wagner, Robert J. Gray, Joseph A. Sparano, Roisin M. Connolly

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

Endocrine therapies are effective in the treatment of hormone receptor (HR)-positive breast cancer, however, de novo or acquired treatment resistance is a significant clinical problem. A potential mechanism of resistance involves changes in gene expression secondary to epigenetic modifications, which might be reversed with the use of histone deacetylase (HDAC) inhibitors such as entinostat. The ENCORE 301 phase II randomized, placebo-controlled study demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS), with the addition of entinostat to exemestane in patients with HR-positive advanced breast cancer with disease progression after prior non-steroidal aromatase inhibitor (AI). These results prompted the development of E2112, a phase III registration trial which is investigating entinostat/placebo in combination with exemestane in patients with locally advanced or metastatic breast cancer who have experienced disease progression after a non-steroidal AI. E2112 aims to validate the preclinical and clinical findings supporting the role of HDAC inhibitors in overcoming resistance to endocrine therapy in breast cancer, and ultimately improve outcomes for patients with advanced breast cancer.

Original languageEnglish (US)
Article number4
Journalnpj Breast Cancer
Volume4
Issue number1
DOIs
StatePublished - Dec 1 2018

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exemestane
Placebos
Hormones
Breast Neoplasms
Aromatase Inhibitors
Histone Deacetylase Inhibitors
Disease Progression
Therapeutics
Epigenomics
Disease-Free Survival
entinostat
Gene Expression
Survival

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

Cite this

E2112 : Randomized phase III trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer. / Yeruva, Sri Lakshmi Hyndavi; Zhao, Fengmin; Miller, Kathy; Tevaarwerk, Amye J.; Wagner, Lynne I.; Gray, Robert J.; Sparano, Joseph A.; Connolly, Roisin M.

In: npj Breast Cancer, Vol. 4, No. 1, 4, 01.12.2018.

Research output: Contribution to journalReview article

Yeruva, Sri Lakshmi Hyndavi ; Zhao, Fengmin ; Miller, Kathy ; Tevaarwerk, Amye J. ; Wagner, Lynne I. ; Gray, Robert J. ; Sparano, Joseph A. ; Connolly, Roisin M. / E2112 : Randomized phase III trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer. In: npj Breast Cancer. 2018 ; Vol. 4, No. 1.
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