Maintenance Olaparib for Germline <i>BRCA</i> -Mutated Metastatic Pancreatic Cancer
Talia GolanFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallPascal HammelFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallMichele ReniFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallEric Van CutsemFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallTeresa MacarullaFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallMichael J. HallFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallJoon-Oh ParkFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallDaniel HochhauserFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallDirk ArnoldFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallDo‐Youn OhFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallAnke Reinacher‐SchickFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallGiampaolo TortoraFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallHana AlgülFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallEileen M. O’ReillyFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallDavid McGuinnessFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallKaren CuiFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallKatia SchliengerFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallGershon Y. LockerFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); VallHedy L. KindlerFrom the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); Vall
2019en
ABI
Аннотация
BACKGROUND: mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib has had antitumor activity in this population. METHODS: mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy. Patients were randomly assigned, in a 3:2 ratio, to receive maintenance olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival, which was assessed by blinded independent central review. RESULTS: Of the 3315 patients who underwent screening, 154 underwent randomization and were assigned to a trial intervention (92 to receive olaparib and 62 to receive placebo). The median progression-free survival was significantly longer in the olaparib group than in the placebo group (7.4 months vs. 3.8 months; hazard ratio for disease progression or death, 0.53; 95% confidence interval [CI], 0.35 to 0.82; P = 0.004). An interim analysis of overall survival, at a data maturity of 46%, showed no difference between the olaparib and placebo groups (median, 18.9 months vs. 18.1 months; hazard ratio for death, 0.91; 95% CI, 0.56 to 1.46; P = 0.68). There was no significant between-group difference in health-related quality of life, as indicated by the overall change from baseline in the global quality-of-life score (on a 100-point scale, with higher scores indicating better quality of life) based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (between-group difference, -2.47 points; 95% CI, -7.27 to 2.33). The incidence of grade 3 or higher adverse events was 40% in the olaparib group and 23% in the placebo group (between-group difference, 16 percentage points; 95% CI, -0.02 to 31); 5% and 2% of the patients, respectively, discontinued the trial intervention because of an adverse event. CONCLUSIONS: mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo. (Funded by AstraZeneca and others; POLO ClinicalTrials.gov number, NCT02184195.).
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