Evidence map›Paper›PMID 40448813›Full record

SynthesisBreast cancer research and treatment2025

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

Nour Maher Mustafa, Mus'ab Theeb Mustafa, Aws Khalid Abushanab, Hamza Muneer Alakhras, Anas Saed Abed, Sereen Ahmad Bani-Said, Laith Sami Othman, Areen Shdaifat

Abstract readSystematic ReviewMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Breast cancer research and treatment, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Nour Maher MustafaFaculty of Medicine, University of Jordan, Amman, Jordan. Nourrmaher2001@gmail.com.
Mus'ab Theeb MustafaFaculty of Medicine, Hashemite University, Zarqa, Jordan.
Aws Khalid AbushanabFaculty of Medicine, Hashemite University, Zarqa, Jordan.
Hamza Muneer AlakhrasFaculty of Medicine, University of Jordan, Amman, Jordan.
Anas Saed AbedFaculty of Medicine, Mutah University, Al-Karak, Jordan.
Sereen Ahmad Bani-SaidFaculty of Medicine, University of Jordan, Amman, Jordan.
Laith Sami OthmanFaculty of Medicine, University of Jordan, Amman, Jordan.
Areen ShdaifatFaculty of Medicine, University of Jordan, Amman, Jordan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHormone receptor-positive (HR+) breast cancer continues to be a significant global challenge, as resistance to endocrine therapy (ET) often reduces its effectiveness. Entinostat (ENT), a novel and selective histone deacetylase inhibitor (HDACi), has been suggested to overcome the resistance. However, there is still ongoing debate regarding its efficacy and safety.

objectiveOur meta-analysis aims to assess the efficacy and safety of ENT plus exemestane (EXE) versus placebo (PL) plus EXE in patients with HR+ breast cancer.

methodsFollowing PRISMA guidelines, a systematic search was conducted across PubMed, Web of Science, and Cochrane Library up to November 2024, resulting in the inclusion of four randomized controlled trials (RCTs) involving 1371 patients. The primary outcomes were progression-free survival (PFS) and overall survival (OS), while secondary outcomes were the objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AEs). Our meta-analysis was prospectively registered in PROSPERO (registration number: CRD42024615056).

resultsOur Analysis showed that ENT + EXE significantly enhanced PFS in the overall HR+ population Hazard Ratio (HR) = 0.79 (95% CI 0.68-0.92; P = 0.003), particularly among human epidermal growth factor receptor-2 (HER2-) negative patients (HR = 0.80; 95% CI 0.68-0.95; P = 0.01) when compared to PL + EXE. However, no significant improvements were noted in OS (HR = 0.91; 95% CI 0.63-1.30; P = 0.60), ORR with relative risk (RR) = 1.37 (95% CI 0.90-2.07; P = 0.14), CBR (RR = 1.15; 95% CI 0.89-1.74; P = 0.29). Furthermore, our safety analysis demonstrated that patients receiving ENT + EXE experienced significantly higher rates of adverse events (AEs) of all grades, with a RR of 1.33 (95% CI 0.99-1.78) and a significant increase in grade ≥ 3 AEs (RR = 3.04; 95% CI 2.52-3.67).

conclusionThe ENT + EXE combination demonstrates significant PFS benefits in HR + breast cancer patients compared to PL + EXE. However, no improvements were seen in OS, ORR, or CBR. In addition, the higher incidence of AEs, especially hematologic and gastrointestinal, highlights the need for careful patient selection and monitoring.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBenzamidesBreast NeoplasmsPyridinesAndrostadienesErb-b2 Receptor Tyrosine KinasesFemaleHumansRandomized Controlled Trials as TopicReceptors, EstrogenReceptors, ProgesteroneTreatment OutcomeAndrostadienesBenzamidesentinostatERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesexemestanePyridinesReceptors, EstrogenReceptors, ProgesteroneBreast cancerEntinostatExemestaneHDACHormone receptor positiveMeta-analysis

Identifiers

PMID40448813

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.