POLO: A randomized phase III trial of olaparib maintenance monotherapy in patients (pts) with metastatic pancreatic cancer (mPC) who have a germline <i>BRCA1/2</i> mutation (g<i>BRCA</i>m).

TPS4152 Background: Defective double-strand DNA break repair caused by a gBRCAm is a risk factor for mPC. In the general population of mPC pts, the prevalence of a gBRCAm may be around 4.5%; but, in some populations of mPC pts, such as Ashkenazi Jews, the prevalence could be up to 15%. Monotherapy with the PARP inhibitor olaparib (Lynparza) has led to tumor responses in a Phase II trial that enrolled gBRCAm pts with a variety of solid tumor types, including in pts with mPC (Kaufman et al JCO 2014: Study 42; NCT01078662). This trial supported preclinical data showing that gBRCAm-defective tumors are intrinsically sensitive to PARP inhibitors, and led to a double-blind, placebo-controlled Phase III trial (NCT02184195; POLO) of olaparib ‘switch maintenance’ monotherapy in pts with mPC and a gBRCAm who have not progressed on first-line platinum-based chemotherapy. Methods: Eligible pts with mPC must have documented disease control after completing ≥16 weeks of a first-line, platinum-based regimen, with a deleterious gBRCAm, which will be assayed and confirmed by Integrated BRACAnalysis (Myriad Genetic Laboratories) during the trial. Pts are randomized (3:2) to olaparib tablets (300 mg orally bd) or placebo. The primary endpoint is PFS, determined by blinded independent central review using RECIST 1.1. The primary PFS analysis will be performed after ≈87 PFS events (≈60% maturity) using a log-rank test. Enrollment began in Q4 2014. As of 16 January 2016, 635 pts have been screened. Of 590 pts for whom BRCA1/2 mutation testing results are currently available, 46 pts (7.8%) with a gBRCAm have been identified: 10 pts were known to have a gBRCAm at screening, while 36/580 (6.2%) had a newly identified gBRCAm. Outside the USA or Israel (where screened populations may be enriched for Ashkenazi Jews), a gBRCAm was newly identified in 23/568 pts (4%). The target number for randomization is ≈145 pts across ≈90 centers worldwide. Clinical trial information: NCT02184195.Country Screened (n) Spain 95 France 85 Korea 81 USA 75 Israel 73 UK 61 Italy 61 Germany 44 Australia 29 Belgium 7 Canada 6 Netherlands 4 Total 621* *The breakdown by country is based on an initial 621 pts screened.

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