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.

Authors

Isabelle Laure Ray-Coquard

Isabelle Laure Ray-Coquard

GINECO Group and Centre Léon Bérard, Lyon, France

Isabelle Laure Ray-Coquard , Philipp Harter , Antonio Gonzalez Martin , Claire Cropet , Sandro Pignata , Keiichi Fujiwara , Christian Marth , Ignace Vergote , Mansoor Raza Mirza , Nicoletta Colombo , Per Rosenberg , Johanna Unelma Maenpaa , Eric Pujade Lauraine

Organizations

GINECO Group and Centre Léon Bérard, Lyon, France, AGO Germany, Essen, Germany, GEICO and MD Anderson Cancer Center Madrid, Madrid, Spain, Statistician GINECO, Lyon, France, MITO, Naples, Italy, GOTIC, Hidaka, Japan, AGO Austria, Innsbruck, Austria, BGOG, University Hospital Leuven, Leuven, Belgium, NSGO, Copenhagen University Hospital, Copenhagen, Denmark, MANGO, Milan, Italy, Nordic Society of Gynecologic Oncology (NSGO) and University Hospital, Linköping, Sweden, NSGO, Tampere, Finland, GINECO, Paris, France

Research Funding

Other

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

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gynecologic Cancer

Track

Gynecologic Cancer

Sub Track

Ovarian Cancer

Clinical Trial Registration Number

NCT02477644

Citation

J Clin Oncol 35, 2017 (suppl; abstr TPS5605)

DOI

10.1200/JCO.2017.35.15_suppl.TPS5605

Abstract #

TPS5605

Poster Bd #

424b

Abstract Disclosures