Olaparib as maintenance treatment following first-line platinum-based chemotherapy (PBC) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC): Phase III POLO trial.

LBA4 Background: Pancreatic cancer (PC) pts with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) have shown response to the PARP inhibitor olaparib (Kaufman 2015). POLO is the first phase III trial to evaluate efficacy of maintenance treatment with a PARP inhibitor in PC. Methods: POLO is an international, randomized, double-blind, placebo-controlled trial of pts with a gBRCAm and pancreatic adenocarcinoma who had received ≥16 weeks of first-line PBC for metastatic disease without progression. Pts were randomized 3:2 to maintenance olaparib (O) tablets (300 mg bid) or placebo (P). Treatment began 4–8 weeks after last PBC dose, continuing until investigator-assessed progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) by blinded independent central review (modified RECIST 1.1). Results: We screened 3315 pts, identified 247 with a gBRCAm, randomized 154 (O 92, P 62), and treated 151 (O 90, P 61). Pt characteristics (O/P): age, median (range) 57 (37–84)/57 (36–75); male, 58%/50%; ECOG performance status 0, 71%/61%. With 104 events, PFS was significantly improved with O vs. P (hazard ratio [HR] 0.53; 95% CI 0.35, 0.82; p = 0.0038; median PFS was 7.4 vs. 3.8 months [mo], respectively) and consistent irrespective of response to prior PBC (complete/partial HR 0.62; stable disease HR 0.50). From 6 mo, the % of pts progression-free in the O arm was more than twice that in the P arm (Table). At the interim overall survival analysis (46% maturity), HR was 0.91 (95% CI 0.56, 1.46; p = 0.68). Grade ≥3 adverse events (AE) occurred in 40% of O- and 23% of P-treated pts; 5.5% and 1.7% of pts, respectively, discontinued treatment due to an AE. Conclusions: Maintenance olaparib provided a statistically significant and clinically meaningful improvement in PFS in mPC pts with a gBRCAm who had not progressed on PBC. Safety was consistent with the known profile for olaparib. POLO is the first phase III trial to validate a biomarker-driven treatment in PC. Clinical trial information: NCT02184195. [Table: see text]