A pilot study of the combination of entinostat with capecitabine in high-risk breast cancer after neoadjuvant therapy.

Abstract

e13107 Background: Breast cancer has an unacceptably high recurrence rate when residual disease is found following neo-adjuvant treatment of high-risk disease. Based on clinical data suggesting an adjuvant role for epigenetic modifying agents in breast cancer and preclinical data suggesting synergistic activity of entinostat combined with capecitabine, we conducted a phase I, open label study of these agents in metastatic breast cancer (MBC). Both agents have published doses for use in combination therapy, but the agents had not previously been combined with each other in a human trial. Methods: A multisite phase I dose escalation study was performed at two academic centers. Patients with pretreated, HER2 negative MBC, and measurable disease were enrolled. Dual dose escalation was performed via a Bayesian partial order continual assessment method. Dose levels ranged from entinostat 3mg to 5mg and capecitabine 800mg/m2 to 1000mg/m2. Results: Thirteen patients with MBC and a median of 4 lines of prior therapy were enrolled across four dose level combinations. The most common toxicities were neutropenia, thrombocytopenia, and palmar- plantar erythrodysesthesia, which were expected toxicities. No new safety signals were observed. One dose-limiting toxicity was observed, which did not exceed a pre-specified toxicity rate of 25%. The median treatment duration was 2.37 months. No partial nor complete responses were observed. The study was halted early prior to entering an expansion phase. Conclusions: The tested dosing combinations of entinostat and capecitabine are likely safe in heavily pretreated metastatic breast cancer patients. Entinostat clinical investigation in breast cancer was halted while this study was ongoing. Clinical trial information: NCT03473639 .