943TiP - Trabectedin and Pegylated Liposomal Doxorubicin (Pld) Versus Carboplatin and Pld in Partially Platinum-Sensitive Ovarian Cancer Patients: Inovatyon Study

Abstract

ABSTRACT Background: The results of a phase III OVA-301 trial demonstrated the superiority of trabectedin (Yondelis®) and PLD over PLD alone in the overall population (n = 672) of patients with relapsed ovarian cancer. Particularly remarkable were the outcomes observed in the partially platinum-sensitive patients (PPS), with platinum-free interval (PFI) 6-12 months (n = 214) that showed a statistically and clinically significant survival advantage. In the trabectedin/PLD arm the administration of subsequent platinum was delayed and these patients survived significantly longer after subsequent platinum. The non-inferiority CALYPSO study in ovarian cancer patients with disease recurrence >6 months reported that the combination of PLD/carboplatin, in the PPS subset, showed longer progression-free survival and less toxicity than the standard carboplatin/paclitaxel combination. The proposed INOVATYON (INternational OVArian cancer patients Treated with YONdelis) phase III, randomized trial compares PLD/carboplatin vs. the non-platinum trabectedin/PLD combination in the PPS population. Trial design: INOVATYON is prospectively designed with the aim to demonstrate that extending PFI with a non-platinum combination prolongs response to subsequent platinum and survival in patients with relapsed PPS ovarian cancer. The enrollment to INOVATYON (EudraCT: 2010-022949-17) has been ongoing from the beginning of 2011 but soon after and until recently the study was put on hold due to PLD worldwide shortage. The primary objective is to demonstrate that trabectedin/PLD prolongs overall survival (OS) over carboplatin/PLD. The primary analysis will require 442 events (∼588 patients) to have an 85% power to detect a 25% reduction in the hazard rate for death (one sided a = 0.02). Randomization 1:1 and stratification by center, chemotherapy line (2nd/3rd), measurable disease (yes/no) and previous anthracyclines-based chemotherapy (yes/no) has been performed. A futility analysis (∼100 events) and an interim analysis (∼two/thirds of events) controlling type I error are pre-specified. An independent data monitoring committee (IDMC) oversees study conduct. Disclosure: All authors have declared no conflicts of interest.