TY - JOUR
T1 - Overall Survival Results from the POLO Trial
T2 - A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer
AU - Kindler, Hedy L.
AU - Hammel, Pascal
AU - Reni, Michele
AU - Van Cutsem, Eric
AU - Macarulla, Teresa
AU - Hall, Michael J.
AU - Park, Joon Oh
AU - Hochhauser, Daniel
AU - Arnold, Dirk
AU - Oh, Do Youn
AU - Reinacher-Schick, Anke
AU - Tortora, Giampaolo
AU - Algül, Hana
AU - O'Reilly, Eileen M.
AU - Bordia, Sonal
AU - McGuinness, David
AU - Cui, Karen
AU - Locker, Gershon Y.
AU - Golan, Talia
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - PURPOSEThe 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 METHODSPatients 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.RESULTSIn 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.CONCLUSIONAlthough 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.
AB - PURPOSEThe 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 METHODSPatients 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.RESULTSIn 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.CONCLUSIONAlthough 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.
UR - http://www.scopus.com/inward/record.url?scp=85142940982&partnerID=8YFLogxK
U2 - 10.1200/JCO.21.01604
DO - 10.1200/JCO.21.01604
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C2 - 35834777
AN - SCOPUS:85142940982
SN - 0732-183X
VL - 40
SP - 3929
EP - 3939
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 34
ER -
