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

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.