E2112: 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

Roisin M. Connolly; Fengmin Zhao; Kathy D. Miller; Min-Jung Lee; Richard L. Piekarz; Karen L. Smith; Ursa A. Brown-Glaberman; Jennifer S. Winn; Bryan A. Faller; Adedayo A. Onitilo; Mark E. Burkard; George T. Budd; Ellis G. Levine; Melanie E. Royce; Peter A. Kaufman; Alexandra Thomas; Jane B. Trepel; Antonio C. Wolff; Joseph A. Sparano

doi:10.1200/JCO.21.00944

Back

E2112: 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

Journal article

Open access

Peer reviewed

E2112: 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

Roisin M. Connolly, Fengmin Zhao, Kathy D. Miller, Min-Jung Lee, Richard L. Piekarz, Karen L. Smith, Ursa A. Brown-Glaberman, Jennifer S. Winn, Bryan A. Faller, Adedayo A. Onitilo, …

Journal of clinical oncology, Vol.39(28), pp.3171-3181

10/01/2021

DOI: 10.1200/JCO.21.00944

PMCID: PMC8478386

PMID: 34357781

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478386View

Published (Version of record) Open Access

Abstract

PURPOSE Endocrine therapy resistance in advanced breast cancer remains a significant clinical problem that may be overcome with the use of histone deacetylase inhibitors such as entinostat. The ENCORE301 phase II study reported improvement in progression-free survival (PFS) and overall survival (OS) with the addition of entinostat to the steroidal aromatase inhibitor (AI) exemestane in advanced hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer. PATIENTS AND METHODS E2112 is a multicenter, randomized, double-blind, placebo-controlled phase III study that enrolled men or women with advanced HR-positive, HER2-negative breast cancer whose disease progressed after nonsteroidal AI. Participants were randomly assigned to exemestane 25 mg by mouth once daily and entinostat (EE) or placebo (EP) 5 mg by mouth once weekly. Primary end points were PFS by central review and OS. Secondary end points included safety, objective response rate, and lysine acetylation change in peripheral blood mononuclear cells between baseline and cycle 1 day 15. RESULTS Six hundred eight patients were randomly assigned during March 2014-October 2018. Median age was 63 years (range 29-91), 60% had visceral disease, and 84% had progressed after nonsteroidal AI in metastatic setting. Previous treatments included chemotherapy (60%), fulvestrant (30%), and cyclin-dependent kinase inhibitor (35%). Most common grade 3 and 4 adverse events in the EE arm included neutropenia (20%), hypophosphatemia (14%), anemia (8%), leukopenia (6%), fatigue (4%), diarrhea (4%), and thrombocytopenia (3%). Median PFS was 3.3 months (EE) versus 3.1 months (EP; hazard ratio = 0.87; 95% CI, 0.67 to 1.13; P = .30). Median OS was 23.4 months (EE) versus 21.7 months (EP; hazard ratio = 0.99; 95% CI, 0.82 to 1.21; P = .94). Objective response rate was 5.8% (EE) and 5.6% (EP). Pharmacodynamic analysis confirmed target inhibition in entinostat-treated patients. CONCLUSION The combination of exemestane and entinostat did not improve survival in AI-resistant advanced HR-positive, HER2-negative breast cancer.

Details

Title: Subtitle: E2112: 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
Creators: Roisin M. Connolly - University College Cork
Fengmin Zhao - Dana-Farber Cancer Institute
Kathy D. Miller - Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Min-Jung Lee - Center for Cancer Research, National Cancer Institute, Bethesda, MD
Richard L. Piekarz - Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD
Karen L. Smith - Sidney Kimmel Comprehensive Cancer Center
Ursa A. Brown-Glaberman - UNM Comprehensive Cancer Center
Jennifer S. Winn - Fox Chase Cancer Center
Bryan A. Faller - New England Baptist Hospital
Adedayo A. Onitilo - Marshfield Clinic, Marshfield, WI
Mark E. Burkard - University of Wisconsin Carbone Cancer Center
George T. Budd - Cleveland Clinic
Ellis G. Levine - Roswell Park Comprehensive Cancer Center
Melanie E. Royce - New Mexico MU-NCORP, Albuquerque, NM
Peter A. Kaufman - University of Vermont
Alexandra Thomas - Wake Forest University
Jane B. Trepel - Center for Cancer Research, National Cancer Institute, Bethesda, MD
Antonio C. Wolff - Sidney Kimmel Comprehensive Cancer Center
Joseph A. Sparano - Montefiore Medical Center
Resource Type: Journal article
Publication Details: Journal of clinical oncology, Vol.39(28), pp.3171-3181
Publisher: American Society of Clinical Oncology (ASCO)
DOI: 10.1200/JCO.21.00944
PMID: 34357781
PMCID: PMC8478386
ISSN: 0732-183X
eISSN: 1527-7755
Number of pages: 11
Language: English
Date published: 10/01/2021
Academic Unit: Internal Medicine
Record Identifier: 9984701258302771

Metrics

4 Record Views

72 Times Cited - Web of Science

See more details