Background: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. ClincalTrials.gov number: NCT02184195.

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib

Arnold D.
Membro del Collaboration Group
;
Tortora G.;Peeters M.
Membro del Collaboration Group
;
Vogel A.;Geva R.;Shai A.;Di Marco M.
Investigation
;
Milella M.
Investigation
;
Santini D.;Tortora G.;Lopez R.;Wall L.;Ejadi S.;Hall M.;Marsh R.;Ryan D.;
2019

Abstract

Background: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. ClincalTrials.gov number: NCT02184195.
Hammel P.; Kindler H.L.; Reni M.; Van Cutsem E.; MacArulla T.; Hall M.J.; Park J.O.; Hochhauser D.; Arnold D.; Oh D.-Y.; Reinacher-Schick A.; Tortora G.; Algul H.; O'Reilly E.M.; McGuinness D.; Cui K.Y.; Joo S.; Yoo H.K.; Patel N.; Golan T.; Chantrill L.; Goldstein D.; Joubert W.; Pavlakis N.; Tognela A.; Van Cutsem E.; Van Fraeyenhove F.; Van Laethem J.-L.; Peeters M.; Dhani N.; Kavan P.; Lemay F.; Adenis A.; Artru P.; Baba-Hamed N.; Belletier C.; Ben Abdelghani M.; Blanc J.-F.; Borg C.; Coriat R.; Deplanque G.; Faroux R.; Follana P.; Guimbaud R.; El Hajbi F.; Hammel P.; Hautefeuille V.; Malka D.; Metges J.-P.; Tougeron D.; Walter T.; Algul H.; Ettrich T.; Hacker U.T.; Hennes E.; Jacobasch L.; Kanzler S.; Pession U.; Reinacher-Schick A.; Scholz C.; Sinn M.; Stein A.; Strassburg C.; Vogel A.; Ben-Shahar M.; Brenner R.; Epelbaum R.; Geva R.; Gluzman A.; Golan T.; Idelevich E.; Kolin M.; Semenisty V.; Shai A.; Stemmer S.; Yarom N.; Celio L.; Conte P.; Garufi C.; Gianni L.; Leonardi F.; Maiello E.; Di Marco M.; Milella M.; Pinto C.; Santini D.; Scartozzi M.; Tortora G.; Vaccaro V.; Vasile E.; Kim J.-W.; Kim J.-W.; Oh D.-Y.; Oh Park J.; Wilmink H.; Gallego R.A.; Ogalla G.D.; Velasco A.G.; Cabanas E.G.; Gomez Martin C.; Ponce C.G.; Saez B.L.; Lopez R.; MacArulla T.; Martin A.M.; Pazo R.; Pijaume C.P.; Rodriguez J.; Yaya-Tur R.; Arora A.; Anthoney D.A.; Jeffrey Evans T.R.; Harrison M.; Hochhauser D.; Palmer D.; Sarker D.; Starling N.; Valle J.; Wall L.; Agajanian R.; Bearden J.; Bekaii-Saab T.; Carter C.; Cohen D.; Distefano A.; Dragovich T.; Ejadi S.; Ford J.; Grabelsky S.; Hall M.; Hochster H.; Hosein P.; Javle M.; Kindler H.; Lacy J.; Laheru D.; Leong S.; Lowery M.; Marsh R.; Noonan A.; Oberstein P.; Ocean A.; O'Reilly E.; Ryan D.; Seery T.; Subramaniam S.; Van Echo D.; Wang-Gillam A.; Weekes C.; Welch S.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/725200
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