The Fntb-609g > C Polymorphism As A Possible Predictive Factor For Efficacy Of Lonafarnib-Treatment? - Exploratory Analysis Of A Randomized Phase Ii Clinical Trial In Stage Iib-Iv Ovarian Cancer, Treated With First Line Platinum-Based Chemotherapy +/- Lonafarnib

e16534 Background: Despite promising preclinical findings regarding clinical utility of farnesyltransferase inhibitors (FTI), such as lonafarnib, success of clinical studies is limited. In some studies, response to FTI was observed in 20-30% of patients, whereas other studies failed to resolve a benefit of lonafarnib, or even showed a negative effect of lonafarnib on the outcome of suboptimally debulked ovarian cancer patients (AGO-OVAR 15 phase II). In this regard, aim of the present study was to investigate clinical utility of a -609Gu003eC polymorphism, located within the promoter core region of the farnesyltransferase s-subunit gene (FNTB), in terms of a molecular biomarker for lonafarnib response. Methods: Influence of -609Gu003eC on FNTB-promoter activity was investigated in vitro by electrophoretic mobility shift assay, luciferase reporter assay and RT-qPCR. Subsequently, 57 out of 105 patients from the prospective, randomized AGO-OVAR 15 phase II trial, treated with carboplatin and paclitaxel ± lonafarnib...