2019 ASCO Annual Meeting!
Session: Plenary Session Including the Distinguished Achievement Award and Science of Oncology Award Lecture
Type: Plenary Session
Time: Sunday June 2, 1:00 PM to 4:00 PM
Location: Hall B1
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.
Gastrointestinal (Noncolorectal) Cancer
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr LBA4)
Author(s): Hedy L. Kindler, Pascal Hammel, Michele Reni, Eric Van Cutsem, Teresa Macarulla Mercade, Michael J. Hall, Joon Oh Park, Daniel Hochhauser, Dirk Arnold, Do-Youn Oh, Anke C. Reinacher-Schick, Giampaolo Tortora, Hana Algül, Eileen Mary O'Reilly, David McGuinness, Karen Cui, Katia Schlienger, Gershon Y. Locker, Talia Golan; The University of Chicago, Chicago, IL; Hôpital Beaujon (AP-HP), Clichy, and University Paris VII, Paris, France; IRCCS Ospedale, San Raffaele Scientific Institute, Milan, Italy; University Hospitals Gasthuisberg, Leuven and KU Leuven, Leuven, Belgium; Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain; Fox Chase Cancer Center, Philadelphia, PA; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; University College London Cancer Institute, London, United Kingdom; Asklepios Tumorzentrum Hamburg AK Altona, Hamburg, Germany; Seoul National University Hospital, Seoul, South Korea; St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany; Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy; Klinikum rechts der Isar, Department of Internal Medicine II, Technische Universität München, Munich, Germany; Memorial Sloan Kettering Cancer Center, New York, NY; AstraZeneca, Cambridge, United Kingdom; AstraZeneca, Gaithersburg, MD; Merck & Co., Inc., Kenilworth, NJ; The Oncology Institute, Sheba Medical Center at Tel-Hashomer, Tel Aviv University, Tel Aviv, Israel
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
N = 92, %
N = 62, %
1. APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma.