Author(s): Hedy L. Kindler, MD1;Pascal Hammel, MD, PhD2;Michele Reni, MD3;Eric Van Cutsem, MD, PhD4;Teresa Macarulla, MD, PhD5;Michael J. Hall, MD6;Joon Oh Park, MD, PhD7;Daniel Hochhauser, MD, PhD8;Dirk Arnold, MD, PhD9;Do-Youn Oh, MD, PhD10;Anke Reinacher-Schick, MD, PhD11;Giampaolo Tortora, MD, PhD12;Hana Algül, MD, PhD, MPH13;Eileen M. O’Reilly, MD14;Sonal Bordia, MD15;David McGuinness, MSc16;Karen Cui, MD, PhD17;Gershon Y. Locker, MD17;and Talia Golan, MD18
PURPOSE
The phase III POLO study demonstrated significant progression-free survival (PFS) benefit for active olaparib maintenance therapy versus placebo for patients with metastatic pancreatic adenocarcinoma and a germline BRCA mutation. Here, we report the final analysis of overall survival (OS) and other secondary end points.
PATIENTS AND METHODS
Patients with a deleterious or suspected deleterious germline BRCA mutation whose disease had not progressed after ≥ 16 weeks of first-line platinum-based chemotherapy were randomly assigned 3:2 to active maintenance olaparib (300 mg twice daily) or placebo. The primary end point was PFS; secondary end points included OS, time to second disease progression or death, time to first and second subsequent cancer therapies or death, time to discontinuation of study treatment or death, and safety and tolerability.
RESULTS
In total, 154 patients were randomly assigned (olaparib, n = 92; placebo, n = 62). No statistically significant OS benefit was observed (median 19.0 v 19.2 months; hazard ratio [HR], 0.83; 95% CI, 0.56 to 1.22; P = .3487). Kaplan-Meier OS curves separated at approximately 24 months, and the estimated 3-year survival after random assignment was 33.9% versus 17.8%, respectively. Median time to first subsequent cancer therapy or death (HR, 0.44; 95% CI, 0.30 to 0.66; P < .0001), time to second subsequent cancer therapy or death (HR, 0.61; 95% CI, 0.42 to 0.89; P = .0111), and time to discontinuation of study treatment or death (HR, 0.43; 95% CI, 0.29 to 0.63; P < .0001) significantly favored olaparib. The HR for second disease progression or death favored olaparib without reaching statistical significance (HR, 0.66; 95% CI, 0.43 to 1.02; P = .0613). Olaparib was well tolerated with no new safety signals.
CONCLUSION
Although no statistically significant OS benefit was observed, the HR numerically favored olaparib, which also conferred clinically meaningful benefits including increased time off chemotherapy and long-term survival in a subset of patients.
Author Affiliations
1The University of Chicago, Chicago, IL
2Paul Brousse Hospital (AP-HP), University Paris-Saclay, Villejuif, France
3IRCCS Ospedale, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
4University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium
5Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain
6Fox Chase Cancer Center, Philadelphia, PA
7Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
8University College London Cancer Institute, London, United Kingdom
9Asklepios Tumorzentrum Hamburg AK Altona, Hamburg, Germany
10Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
11St Josef-Hospital, Ruhr University Bochum, Bochum, Germany
12Fondazione Policlinico A Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
13Klinikum rechts der Isar, Comprehensive Cancer Center Munich TUM, Technische Universität München, Munich, Germany
14Memorial Sloan Kettering Cancer Center, New York, NY
15Merck & Co Inc, Kenilworth, NJ
16AstraZeneca, Cambridge, United Kingdom
17AstraZeneca, Gaithersburg, MD
18The Oncology Institute, Sheba Medical Center at Tel-Hashomer, Tel Aviv University, Tel Aviv, Israel
