Preoperative olaparib in early-stage endometrial cancer (EC): A phase 0, window of opportunity trial to evaluate the PARP inhibition effect, targeting cell cycle-related proteins (POLEN study).

5598Background: Olaparib (AZD2281, KU-0059436) is a poly ADP ribose polymerase (PARP) inhibitor. Biomarkers that predict a response to olaparib in EC are not fully established. The aim of this study is to identify pharmacodynamic and pharmacogenetic biomarkers associated with a short term exposure to olaparib in type I primary EC surgical patients (pts). Methods: In this phase 0, multicenter, single arm, window of opportunity trial, women diagnosed with type I primary EC received olaparib tablets (oral 300mg/BID; 4 weeks) before surgery. Biological effects were evaluated by comparing the initial biopsy and the tumor tissue at surgery. The primary endpoints were the significant inhibition of cyclin D1, Ki67 and active caspase 3 activity. Secondary objectives included the correlation between PARP inhibition and cell proliferation, angiogenesis and tumor-tissue biomarkers. The predictive role of PTEN, PMS2 and MSH6 mutations were evaluated. We control multiple testing issues with a false discovery rate (FDR)...