Entinostat plus exemestane for hormone receptor-positive advanced breast cancer: long-term overall survival results from the EOC103A3101 randomized controlled trial

Original title: Entinostat plus exemestane for hormone receptor-positive advanced breast cancer: long-term overall survival results from the EOC103A3101 randomized controlled trial.

By Wang, Zhang, Hu +15Signal transduction and targeted therapyOct 20, 2026

Score█████░░░░░5.0

Key numbers

95% confidence interval
95% CI
65.5% of patients in the

VerdictWorth a reader's time today.

Read the original

Abstract

The addition of entinostat, a histone deacetylase inhibitor, to exemestane has demonstrated improved progression-free survival (PFS) in hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) following endocrine therapy failure in the EOC103A3101 randomized trial (NCT03538171). This study reports long-term overall survival (OS) results. In this study, 354 patients with HR + /HER2- ABC that had recurred or progressed after endocrine therapy were randomized (2:1) to receive entinostat plus exemestane (n = 235) or placebo plus exemestane (n = 119). After a median follow-up of 31.8 months, the median OS was 38.6 months (95% confidence interval [CI]: 29.6-44.0) in the entinostat-exemestane group versus 29.2 months (95% CI: 22.5-41.6) in the placebo-exemestane group (hazard ratio [HR] 0.83, 95% CI: 0.62-1.10, P = 0.184). The entinostat-exemestane group demonstrated more pronounced OS benefits when adjusting subsequent antitumor therapies such as cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, or the combination of endocrine therapy, CDK4/6 inhibitors, and chemotherapy. The sensitivity analysis based on the per-protocol set showed more significant OS benefits. The median time to post-discontinuation chemotherapy and chemotherapy-free survival in the entinostat-exemestane group were 11.7 and 9.3 months, respectively, compared to 6.8 and 5.6 months in the placebo-exemestane group (both P < 0.05). Grade ≥3 treatment-emergent adverse events occurred in 65.5% of patients in the entinostat-exemestane group, without new safety signals observed. In conclusion, among patients with HR + /HER2- ABC after endocrine therapy failure, entinostat plus exemestane was associated with a numerically longer OS, with an acceptable safety profile.

Jiani Wang, Qingyuan Zhang, Xichun Hu, Tao Sun, Wei Li, Quchang Ouyang, Jingfen Wang, Zhongsheng Tong, Min Yan, Huiping Li, Xiaohua Zeng, Changping Shan, Xian Wang, Jian Zhang, Yue Zhang, Liang Zhang, Hongyan Shang, Binghe Xu

The editor's rubric

Heuristic review

Leverage2 / 5: Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).; 10% of this desk’s rubric
Magnitude3 / 5: Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.; 20% of this desk’s rubric
Evidence4 / 5: Strong: large scale, preregistered, independently replicated, or a well-powered randomized trial.; 32% of this desk’s rubric
Novelty2 / 5: A new combination of known ideas.; 8% of this desk’s rubric
Trajectory2 / 5: Some room to improve with obvious engineering.; 5% of this desk’s rubric
Stakes3 / 5: Meaningful benefit to many people within a few years.; 25% of this desk’s rubric

Dimension	Level	Weight	What that level means
Leverage	██░░░ 2	10%	Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).
Magnitude	███░░ 3	20%	Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.
Evidence	████░ 4	32%	Strong: large scale, preregistered, independently replicated, or a well-powered randomized trial.
Novelty	██░░░ 2	8%	A new combination of known ideas.
Trajectory	██░░░ 2	5%	Some room to improve with obvious engineering.
Stakes	███░░ 3	25%	Meaningful benefit to many people within a few years.

Editor’s rationale

Heuristic triage from title and abstract text only, not a reading of the paper. Cues found: gains (efficacy); design (randomized, placebo-controlled, registered); verification (confidence interval, p-value); scale (improves with scale); stakes (mortality, major disease, prevention or cure).

How the score was computed

rank-2026-10-18

Score█████░░░░░5.0

Score = 10 × (80% × adjusted merit / 10 + 10% × attention + 10% × freshness)

Desks place stronger verdicts first, then use this score to order work within the same verdict.

Merit: 6.2 / 10; Weighted rubric, evidence-gated.
Adjusted merit: 5.1 / 10; Shrunk toward the desk prior by editor confidence (50%).
Attention: 0%; Citations, upvotes, points, mentions.
Freshness: 92%; Half-life decay since publication.

Citations0 (reference 20, via openalex, Oct 21, 2026, 06:17 UTC)

The record

Reviewed by heuristic-v7 on Oct 21, 2026, 06:17 UTC. Paper type: clinical.
Categories: Randomized Controlled Trial, Journal Article, Humans, Breast Neoplasms, Benzamides, Pyridines, Androstadienes, Receptors, Estrogen, Receptors, Progesterone, Antineoplastic Combined Chemotherapy Protocols
TOP, No.5 in the Medicine edition of October 21, 2026.