Endocrine based therapy is a backbone of treatment with proven clinical benefits for women HR+, HER2- breast cancer. Over time, disruption of estrogen mediated signaling within the breast cancer cell results in acquired resistance to hormone therapy. Entinostat is thought to re-sensitize these cells to endocrine therapy.
In a phase 2 randomized, placebo-controlled study, ENCORE 301, entinostat demonstrated a significant (8 mo) improvement in overall survival in combination with exemestane vs exemestane alone. This result led to Breakthrough Therapy status from the FDA, and the initiation of E2112, a phase 3 registration enabling study designed to evaluate entinostat in combination with exemestane in HR+, HER2- metastatic. Enrollment in E2112 was recently closed after a total of 608 patients accrued to the trial, and results of the overall survival analysis are anticipated sometime in 2019.