PAOLA-1: An ENGOT/GCIG phase III trial of olaparib versus placebo combined with bevacizumab as maintenance treatment in patients with advanced ovarian cancer following first-line platinum-based chemotherapy plus bevacizumab.

Abstract

TPS5605 Background: Olaparib (Lynparza) is an oral PARP inhibitor indicated in the EU for the maintenance treatment of patients (pts) with platinum-sensitive relapsed BRCA-mutated high grade serous ovarian cancer (HGSOC). Bevacizumab is an anti-VEGF monoclonal antibody indicated in the EU in first line or relapse for the treatment of OC in combination with specific chemotherapeutic agents. Bevacizumab treatment is associated with increasing hypoxia-induced homologous recombination repair deficiencies in tumor cells, and is hypothesized to increase ovarian tumor sensitivity to olaparib. Methods: PAOLA-1 (ENGOT-ov25) is a randomized, placebo-controlled trial evaluating the efficacy and safety of olaparib (tablet formulation) in pts with advanced HGSOC receiving bevacizumab maintenance therapy. Eligible pts are those in complete or partial response following first-line platinum chemotherapy plus bevacizumab, and for whom bevacizumab maintenance therapy is planned. Approximately 762 European and 24 Japanese pts will be randomized 2:1 to olaparib 300 mg twice daily or placebo for up to 24 months. All pts will receive standard maintenance care of bevacizumab (15 mg/kg every three weeks) for up to 15 months. Primary objective: PFS1 according to RECIST 1.1 Secondary objectives: PFS2, OS, Safety, PRO/QoL, TFST, TSST All pts will undergo tumor BRCA testing prior to randomization. Central BRCA testing (tumor) will be performed in five screening platforms in France. Tumor BRCA test results have to be available within two months of sample provision. PFS will be evaluated using a log-rank test stratified by response to first-line treatment and BRCA mutation status. Treatment effect hazard ratio of 0.7 is expected and final PFS1 analysis will be performed after 372 events. The first pt from eight ENGOT groups plus Japan (10 participating countries) was randomized in July 2015. As of 31 January 2017, 549 pts have been randomized. The median period between the provision of a tumor sample and returned BRCA test result is 40 days. Accrual is expected to be complete before July 2017. Clinical trial information: NCT02477644.