Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2021
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.
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
83 citing papers in PubMed, 4 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- Efficacy and safety of entinostat plus exemestane in hormone receptor-positive breast cancer: a systematic review meta-analysis of randomized controlled trials.Breast cancer research and treatment · 2025Pooled it
- Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors.Current oncology (Toronto, Ont.) · 2025Pooled it
- Efficacy and Safety Profile of Histone Deacetylase Inhibitors for Metastatic Breast Cancer: A Meta-Analysis.Frontiers in oncology · 2022Pooled it
- Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.Annals of oncology : official journal of the European Society for Medical Oncology · 2021Guideline
- Entinostat in patients with relapsed or refractory abdominal neuroendocrine tumors.The oncologist · 2024Trial
- Impact of Muscle Measures on Outcome in Patients Receiving Endocrine Therapy for Metastatic Breast Cancer: Analysis of ECOG-ACRIN E2112.Journal of the National Comprehensive Cancer Network : JNCCN · 2023Trial
- 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 pharmaceutica Sinica. B · 2023Trial
- Efficacy and exploratory biomarker analysis of entinostat plus exemestane in advanced or recurrent breast cancer: phase II randomized controlled trial.Japanese journal of clinical oncology · 2023Trial
- Pharmacological chromatin remodeling enhances response to estrogen therapy in ERMolecular oncology · 2026Article
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Mechanisms of breast cancer dormancy in bone metastasis.Clinical & experimental metastasis · 2026Review
- HDAC3 represses Nrf2-GDF11 signaling to drive chondrocyte adipogenesis in temporomandibular joint osteoarthritis.Journal of advanced research · 2026Article
- Decoding the Snail transcriptional network: its role in cancer progression and therapy.Biology direct · 2026Review
- Targeted Therapies for Each Subtype of Breast Cancer.MedComm · 2026Review
- Targeting microbiome-driven epigenetic modifications: a new frontier in breast cancer treatment.Clinical epigenetics · 2026Review
- HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives.RSC advances · 2026Review
- Epigenetic regulation in cancer chemoresistance and combined therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Epigenetic and mitoepigenetic regulation in cancer and therapeutic perspectives.Frontiers in pharmacology · 2026Review
- Exploring KAT6 as a therapeutic target in breast cancer: epigenetic approaches for precision medicine.NPJ breast cancer · 2025Review
- Lysine Acetyltransferase 6 in Health and Disease.MedComm · 2025Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 15 institutions in 2 countries.
Funding
Abstract
purposeEndocrine 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
methodsE2112 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.
resultsSix 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;
conclusionThe combination of exemestane and entinostat did not improve survival in AI-resistant advanced HR-positive, HER2-negative breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.