Combination Therapy Under Study in Treatment-Resistant Breast Cancer
Posted: Wednesday, April 11, 2018
Adding entinostat to endocrine therapy may improve outcomes in patients with locally advanced or metastatic breast cancer whose disease progressed after a nonsteroidal aromatase inhibitor. Roisin M. Connelly, MB BCh, MD, of Johns Hopkins University, Baltimore, and colleagues are studying this combination strategy in the E2112 trial, according to an article published in Nature. If the findings from this phase III trial confirm those from the phase II ENCORE 301 trial, the investigators believe the U.S. Food and Drug Administration (FDA) may consider approval of this regimen for patients with hormone receptor–positive advanced breast cancer.
Entinostat is a selective histone deacetylase (HDAC) inhibitor not currently approved by regulatory agencies for any indication. However, the combination of entinostat and exemestane was granted Breakthrough Therapy designation by the FDA, and this study was developed with input from the FDA.
A total of 600 patients will be enrolled in this ongoing international, randomized, double-blinded, placebo-controlled trial, with 300 patients to be treated with entinostat and exemestane and 300 patients to be treated with exemestane and placebo. Both progression-free and overall survival are primary study endpoints. In addition, to identify potential biomarkers of efficacy of this combination therapy, tumor and blood samples will be collected from enrolled patients. As reported in ENCORE 301, adverse events associated with entinostat and exemestane treatment included fatigue, weight loss, gastrointestinal toxicity, hematologic toxicity, dyspnea, and peripheral edema.