675PDPOLO: Health-related quality of life (HRQoL) of olaparib maintenance treatment versus placebo in patients with a germline BRCA mutation and metastatic pancreatic cancer (mPC)
Abstract Background In the Phase III POLO trial (NCT02184195) patients (pts) with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and mPC derived a statistically significant and clinically meaningful progression-free survival benefit from maintenance olaparib compared with placebo. HRQoL assessment...
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| Veröffentlicht in: | Annals of oncology 2019-10, Vol.30 (Supplement_5) |
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| creator | Hammel, P Kindler, H L Reni, M Van Cutsem, E Macarulla Mercade, T Hall, M J Park, J O Hochhauser, D Arnold, D Oh, D-Y Reinacher-Schick, A Tortora, G Algül, H O’Reilly, E M McGuinness, D Cui, K Y Joo, S Yoo, H K Patel, N Golan, T |
| description | Abstract
Background
In the Phase III POLO trial (NCT02184195) patients (pts) with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and mPC derived a statistically significant and clinically meaningful progression-free survival benefit from maintenance olaparib compared with placebo. HRQoL assessment was a predefined secondary objective.
Methods
Pts with a gBRCAm and mPC whose disease had not progressed during first-line platinum-based chemotherapy were randomized to receive maintenance olaparib tablets (300 mg bid) or placebo. Pts completed the EORTC QLQ-C30 questionnaire at baseline and every 4 wks until discontinuation, with calculated scores ranging from 1–100. A change of ≥ 10 points was predefined as clinically meaningful improvement (increase) or deterioration (decrease) for global HRQoL and physical function score. Overall adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TCMD) was analysed using a log-rank test.
Results
Analyses were conducted in 89/92 olaparib pts and 58/62 placebo pts with evaluable baseline forms (overall compliance was 96.6% and 94.8%). There was no difference between arms for global HRQoL score (Table). The adjusted mean difference for physical function scale did not reach the threshold considered to be clinically meaningful. Global HRQoL and physical function remained relatively stable over time. There was no difference in TCMD for olaparib versus placebo for global HRQoL (median 21.2 vs 6.0 mo, respectively; hazard ratio 0.72 [95% CI 0.41–1.27]) or physical function (medians not reached, 1.38 [0.73–2.63]).
Table:675PDGlobal HRQoLPhysical functionMaintenance olaparibPlaceboMaintenance olaparibPlaceboAbsolute score, mean (n)Baseline70.4 (89)74.3 (58)83.3 (89)84.9 (58)Week 1273.6 (66)74.1 (36)84.4 (67)85.4 (36)Week 2473.4 (41)NC87.4 (43)NCWeek 4879.0 (23)NC89.6 (23)NCOverall change from baseline*Adjusted mean ± SE (n)−1.2±1.4 (84)1.3±1.9 (54)−2.1±1.3 (84)2.4± 1.7 (54)Between group difference (95% CI)−2.5 (−7.3, 2.3)−4.5 (−8.7, −0.2)P value0.310.04*Pts had to have baseline and ≥1 post-baseline assessmentNC, not calculated due to insufficient numbers of values; SE, standard error
Conclusions
HRQoL was preserved during maintenance olaparib treatment with no meaningful difference versus placebo. Findings support the observed clinical benefit of maintenance olaparib in pts with a gBRCAm and mPC.
Clinical trial identification
NCT02184195.
E |
| doi_str_mv | 10.1093/annonc/mdz247.003 |
| format | Article |
| fullrecord | <record><control><sourceid>oup</sourceid><recordid>TN_cdi_oup_primary_10_1093_annonc_mdz247_003</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/annonc/mdz247.003</oup_id><sourcerecordid>10.1093/annonc/mdz247.003</sourcerecordid><originalsourceid>FETCH-oup_primary_10_1093_annonc_mdz247_0033</originalsourceid><addsrcrecordid>eNqVkEtOw0AQREcIJMznAOx6mUg4Gdv5YHZgQF5EionYWx27TQbNx8yMicK1uCC2wgVYdZWqq1t6jN1EfBLxNJmi1kZXU1V_x7PlhPPkhAXRfJGGd3wWnbKAp3ESLufJ7JxdOPfBOV-kcRqwn8VyXjwV69X6HnJC6XehJYmeavjsUAp_ANOAFA3BKN-8mtV48EZii1ZsQaHQnjTqisBbQq9Ie_gi6zoHrcSKtgaEhha96BMHe-F3gPBOVkmhCR432QOozve50YC6BkUe3eCrvqWr4Wgvq-GFhZEqsvEVO2tQOrr-m5fs9uX5LctD07Vla4VCeygjXg5gyiOY8gim7MEk_1z_BZ84b6o</addsrcrecordid><sourcetype>Publisher</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>675PDPOLO: Health-related quality of life (HRQoL) of olaparib maintenance treatment versus placebo in patients with a germline BRCA mutation and metastatic pancreatic cancer (mPC)</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Hammel, P ; Kindler, H L ; Reni, M ; Van Cutsem, E ; Macarulla Mercade, T ; Hall, M J ; Park, J O ; Hochhauser, D ; Arnold, D ; Oh, D-Y ; Reinacher-Schick, A ; Tortora, G ; Algül, H ; O’Reilly, E M ; McGuinness, D ; Cui, K Y ; Joo, S ; Yoo, H K ; Patel, N ; Golan, T</creator><creatorcontrib>Hammel, P ; Kindler, H L ; Reni, M ; Van Cutsem, E ; Macarulla Mercade, T ; Hall, M J ; Park, J O ; Hochhauser, D ; Arnold, D ; Oh, D-Y ; Reinacher-Schick, A ; Tortora, G ; Algül, H ; O’Reilly, E M ; McGuinness, D ; Cui, K Y ; Joo, S ; Yoo, H K ; Patel, N ; Golan, T</creatorcontrib><description><![CDATA[Abstract
Background
In the Phase III POLO trial (NCT02184195) patients (pts) with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and mPC derived a statistically significant and clinically meaningful progression-free survival benefit from maintenance olaparib compared with placebo. HRQoL assessment was a predefined secondary objective.
Methods
Pts with a gBRCAm and mPC whose disease had not progressed during first-line platinum-based chemotherapy were randomized to receive maintenance olaparib tablets (300 mg bid) or placebo. Pts completed the EORTC QLQ-C30 questionnaire at baseline and every 4 wks until discontinuation, with calculated scores ranging from 1–100. A change of ≥ 10 points was predefined as clinically meaningful improvement (increase) or deterioration (decrease) for global HRQoL and physical function score. Overall adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TCMD) was analysed using a log-rank test.
Results
Analyses were conducted in 89/92 olaparib pts and 58/62 placebo pts with evaluable baseline forms (overall compliance was 96.6% and 94.8%). There was no difference between arms for global HRQoL score (Table). The adjusted mean difference for physical function scale did not reach the threshold considered to be clinically meaningful. Global HRQoL and physical function remained relatively stable over time. There was no difference in TCMD for olaparib versus placebo for global HRQoL (median 21.2 vs 6.0 mo, respectively; hazard ratio 0.72 [95% CI 0.41–1.27]) or physical function (medians not reached, 1.38 [0.73–2.63]).
Table:675PDGlobal HRQoLPhysical functionMaintenance olaparibPlaceboMaintenance olaparibPlaceboAbsolute score, mean (n)Baseline70.4 (89)74.3 (58)83.3 (89)84.9 (58)Week 1273.6 (66)74.1 (36)84.4 (67)85.4 (36)Week 2473.4 (41)NC87.4 (43)NCWeek 4879.0 (23)NC89.6 (23)NCOverall change from baseline*Adjusted mean ± SE (n)−1.2±1.4 (84)1.3±1.9 (54)−2.1±1.3 (84)2.4± 1.7 (54)Between group difference (95% CI)−2.5 (−7.3, 2.3)−4.5 (−8.7, −0.2)P value0.310.04*Pts had to have baseline and ≥1 post-baseline assessmentNC, not calculated due to insufficient numbers of values; SE, standard error
Conclusions
HRQoL was preserved during maintenance olaparib treatment with no meaningful difference versus placebo. Findings support the observed clinical benefit of maintenance olaparib in pts with a gBRCAm and mPC.
Clinical trial identification
NCT02184195.
Editorial acknowledgement
Debbi Gorman, from Mudskipper Business, Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Legal entity responsible for the study
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Funding
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Disclosure
P. Hammel: Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution), Non-remunerated activity/ies: Erythec; Honoraria (self), Research grant / Funding (institution): Halozyme. H.L. Kindler: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Aldeyra Therapeutics; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer-Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Erytech; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Ipsen Pharmaceuticals; Advisory / Consultancy: Kyowa; Advisory / Consultancy, Travel / Accommodation / Expenses: Paredox Therapeutics; Research grant / Funding (institution): Aduro; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Polaris; Research grant / Funding (institution): Verastem. M. Reni: Honoraria (self), Research grant / Funding (institution), Non-remunerated activity/ies: Celgene; Honoraria (self): Baxalta; Honoraria (self): Shire; Honoraria (self): Eli-Liily; Honoraria (self): Pfizer; Honoraria (self): Novocure; Honoraria (self): Novartis; Advisory / Consultancy, Steering committee member: AstraZeneca; Advisory / Consultancy, Steering committee member: Boston Pharmaceuticals. E. Van Cutsem: Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bristol-Myers Squibb. T. Macarulla Mercade: Advisory / Consultancy: Genzyme; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi Aventis; Advisory / Consultancy: Shire; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Baxalta; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Travel / Accommodation / Expenses: H3 Biomedicine; Advisory / Consultancy: QED Therapeutics; Research grant / Funding (institution): Agios pharmaceuticals, Aslan pharmaceuticals; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Halozyme, Inc, Immunomedics, Merrimack, Millennium; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis Farmaceutica S.A.; Research grant / Funding (institution): Novocure GmBH; Research grant / Funding (institution): Oncomed, Pharmacyclics; Research grant / Funding (institution): Pfizer S.L.U.; Travel / Accommodation / Expenses: Merck. M.J. Hall: Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: AstraZeneca; Travel / Accommodation / Expenses, Non-remunerated activity/ies, Non-remunerated activities relate to collaborative research: Caris Life Sciences; Non-remunerated activity/ies, Collaborative research: Myriad; Non-remunerated activity/ies, Collaborative research: Ambry; Non-remunerated activity/ies, Collaborative research: Invitae; Non-remunerated activity/ies, Collaborative research: Foundation Medicine; Non-remunerated activity/ies: Merck. J.O. Park: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Celgene; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Shire; Advisory / Consultancy: Merck; Advisory / Consultancy: Sereno. D. Arnold: Honoraria (self): AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Bayer; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self): Biocompatibles; Honoraria (self): Eli Lilly; Honoraria (self), Non-remunerated activity/ies: Merck Sharpe & Dohme; Honoraria (self), Non-remunerated activity/ies: Servier; Honoraria (self), Non-remunerated activity/ies: Sanofi; Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self): Terumo; Honoraria (self): Sirtex. D. Oh: Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech/ Roche; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Bayer; Advisory / Consultancy: Taiho; Advisory / Consultancy: Aslan; Advisory / Consultancy: Halozyme. A. Reinacher-Schick: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Baxalta; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Research grant / Funding (institution): Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Merck Sharpe & Dohme; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: Sanofi-Aventis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): AstraZeneca. G. Tortora: Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis. H. Algül: Honoraria (self): Celgene; Honoraria (self), Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): Chugai. E.M. O’Reilly: Advisory / Consultancy, Including spouse: 3DMedcare, Boston Scientific, CytomX, Daiichi, Debio, Delcath, Exelixis, Alignmed, An]]></description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdz247.003</identifier><language>eng</language><publisher>Oxford University Press</publisher><ispartof>Annals of oncology, 2019-10, Vol.30 (Supplement_5)</ispartof><rights>European Society for Medical Oncology 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Hammel, P</creatorcontrib><creatorcontrib>Kindler, H L</creatorcontrib><creatorcontrib>Reni, M</creatorcontrib><creatorcontrib>Van Cutsem, E</creatorcontrib><creatorcontrib>Macarulla Mercade, T</creatorcontrib><creatorcontrib>Hall, M J</creatorcontrib><creatorcontrib>Park, J O</creatorcontrib><creatorcontrib>Hochhauser, D</creatorcontrib><creatorcontrib>Arnold, D</creatorcontrib><creatorcontrib>Oh, D-Y</creatorcontrib><creatorcontrib>Reinacher-Schick, A</creatorcontrib><creatorcontrib>Tortora, G</creatorcontrib><creatorcontrib>Algül, H</creatorcontrib><creatorcontrib>O’Reilly, E M</creatorcontrib><creatorcontrib>McGuinness, D</creatorcontrib><creatorcontrib>Cui, K Y</creatorcontrib><creatorcontrib>Joo, S</creatorcontrib><creatorcontrib>Yoo, H K</creatorcontrib><creatorcontrib>Patel, N</creatorcontrib><creatorcontrib>Golan, T</creatorcontrib><title>675PDPOLO: Health-related quality of life (HRQoL) of olaparib maintenance treatment versus placebo in patients with a germline BRCA mutation and metastatic pancreatic cancer (mPC)</title><title>Annals of oncology</title><description><![CDATA[Abstract
Background
In the Phase III POLO trial (NCT02184195) patients (pts) with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and mPC derived a statistically significant and clinically meaningful progression-free survival benefit from maintenance olaparib compared with placebo. HRQoL assessment was a predefined secondary objective.
Methods
Pts with a gBRCAm and mPC whose disease had not progressed during first-line platinum-based chemotherapy were randomized to receive maintenance olaparib tablets (300 mg bid) or placebo. Pts completed the EORTC QLQ-C30 questionnaire at baseline and every 4 wks until discontinuation, with calculated scores ranging from 1–100. A change of ≥ 10 points was predefined as clinically meaningful improvement (increase) or deterioration (decrease) for global HRQoL and physical function score. Overall adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TCMD) was analysed using a log-rank test.
Results
Analyses were conducted in 89/92 olaparib pts and 58/62 placebo pts with evaluable baseline forms (overall compliance was 96.6% and 94.8%). There was no difference between arms for global HRQoL score (Table). The adjusted mean difference for physical function scale did not reach the threshold considered to be clinically meaningful. Global HRQoL and physical function remained relatively stable over time. There was no difference in TCMD for olaparib versus placebo for global HRQoL (median 21.2 vs 6.0 mo, respectively; hazard ratio 0.72 [95% CI 0.41–1.27]) or physical function (medians not reached, 1.38 [0.73–2.63]).
Table:675PDGlobal HRQoLPhysical functionMaintenance olaparibPlaceboMaintenance olaparibPlaceboAbsolute score, mean (n)Baseline70.4 (89)74.3 (58)83.3 (89)84.9 (58)Week 1273.6 (66)74.1 (36)84.4 (67)85.4 (36)Week 2473.4 (41)NC87.4 (43)NCWeek 4879.0 (23)NC89.6 (23)NCOverall change from baseline*Adjusted mean ± SE (n)−1.2±1.4 (84)1.3±1.9 (54)−2.1±1.3 (84)2.4± 1.7 (54)Between group difference (95% CI)−2.5 (−7.3, 2.3)−4.5 (−8.7, −0.2)P value0.310.04*Pts had to have baseline and ≥1 post-baseline assessmentNC, not calculated due to insufficient numbers of values; SE, standard error
Conclusions
HRQoL was preserved during maintenance olaparib treatment with no meaningful difference versus placebo. Findings support the observed clinical benefit of maintenance olaparib in pts with a gBRCAm and mPC.
Clinical trial identification
NCT02184195.
Editorial acknowledgement
Debbi Gorman, from Mudskipper Business, Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Legal entity responsible for the study
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Funding
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Disclosure
P. Hammel: Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution), Non-remunerated activity/ies: Erythec; Honoraria (self), Research grant / Funding (institution): Halozyme. H.L. Kindler: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Aldeyra Therapeutics; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer-Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Erytech; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Ipsen Pharmaceuticals; Advisory / Consultancy: Kyowa; Advisory / Consultancy, Travel / Accommodation / Expenses: Paredox Therapeutics; Research grant / Funding (institution): Aduro; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Polaris; Research grant / Funding (institution): Verastem. M. Reni: Honoraria (self), Research grant / Funding (institution), Non-remunerated activity/ies: Celgene; Honoraria (self): Baxalta; Honoraria (self): Shire; Honoraria (self): Eli-Liily; Honoraria (self): Pfizer; Honoraria (self): Novocure; Honoraria (self): Novartis; Advisory / Consultancy, Steering committee member: AstraZeneca; Advisory / Consultancy, Steering committee member: Boston Pharmaceuticals. E. Van Cutsem: Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bristol-Myers Squibb. T. Macarulla Mercade: Advisory / Consultancy: Genzyme; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi Aventis; Advisory / Consultancy: Shire; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Baxalta; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Travel / Accommodation / Expenses: H3 Biomedicine; Advisory / Consultancy: QED Therapeutics; Research grant / Funding (institution): Agios pharmaceuticals, Aslan pharmaceuticals; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Halozyme, Inc, Immunomedics, Merrimack, Millennium; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis Farmaceutica S.A.; Research grant / Funding (institution): Novocure GmBH; Research grant / Funding (institution): Oncomed, Pharmacyclics; Research grant / Funding (institution): Pfizer S.L.U.; Travel / Accommodation / Expenses: Merck. M.J. Hall: Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: AstraZeneca; Travel / Accommodation / Expenses, Non-remunerated activity/ies, Non-remunerated activities relate to collaborative research: Caris Life Sciences; Non-remunerated activity/ies, Collaborative research: Myriad; Non-remunerated activity/ies, Collaborative research: Ambry; Non-remunerated activity/ies, Collaborative research: Invitae; Non-remunerated activity/ies, Collaborative research: Foundation Medicine; Non-remunerated activity/ies: Merck. J.O. Park: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Celgene; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Shire; Advisory / Consultancy: Merck; Advisory / Consultancy: Sereno. D. Arnold: Honoraria (self): AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Bayer; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self): Biocompatibles; Honoraria (self): Eli Lilly; Honoraria (self), Non-remunerated activity/ies: Merck Sharpe & Dohme; Honoraria (self), Non-remunerated activity/ies: Servier; Honoraria (self), Non-remunerated activity/ies: Sanofi; Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self): Terumo; Honoraria (self): Sirtex. D. Oh: Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech/ Roche; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Bayer; Advisory / Consultancy: Taiho; Advisory / Consultancy: Aslan; Advisory / Consultancy: Halozyme. A. Reinacher-Schick: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Baxalta; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Research grant / Funding (institution): Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Merck Sharpe & Dohme; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: Sanofi-Aventis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): AstraZeneca. G. Tortora: Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis. H. Algül: Honoraria (self): Celgene; Honoraria (self), Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): Chugai. E.M. O’Reilly: Advisory / Consultancy, Including spouse: 3DMedcare, Boston Scientific, CytomX, Daiichi, Debio, Delcath, Exelixis, Alignmed, An]]></description><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqVkEtOw0AQREcIJMznAOx6mUg4Gdv5YHZgQF5EionYWx27TQbNx8yMicK1uCC2wgVYdZWqq1t6jN1EfBLxNJmi1kZXU1V_x7PlhPPkhAXRfJGGd3wWnbKAp3ESLufJ7JxdOPfBOV-kcRqwn8VyXjwV69X6HnJC6XehJYmeavjsUAp_ANOAFA3BKN-8mtV48EZii1ZsQaHQnjTqisBbQq9Ie_gi6zoHrcSKtgaEhha96BMHe-F3gPBOVkmhCR432QOozve50YC6BkUe3eCrvqWr4Wgvq-GFhZEqsvEVO2tQOrr-m5fs9uX5LctD07Vla4VCeygjXg5gyiOY8gim7MEk_1z_BZ84b6o</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>Hammel, P</creator><creator>Kindler, H L</creator><creator>Reni, M</creator><creator>Van Cutsem, E</creator><creator>Macarulla Mercade, T</creator><creator>Hall, M J</creator><creator>Park, J O</creator><creator>Hochhauser, D</creator><creator>Arnold, D</creator><creator>Oh, D-Y</creator><creator>Reinacher-Schick, A</creator><creator>Tortora, G</creator><creator>Algül, H</creator><creator>O’Reilly, E M</creator><creator>McGuinness, D</creator><creator>Cui, K Y</creator><creator>Joo, S</creator><creator>Yoo, H K</creator><creator>Patel, N</creator><creator>Golan, T</creator><general>Oxford University Press</general><scope/></search><sort><creationdate>20191001</creationdate><title>675PDPOLO: Health-related quality of life (HRQoL) of olaparib maintenance treatment versus placebo in patients with a germline BRCA mutation and metastatic pancreatic cancer (mPC)</title><author>Hammel, P ; Kindler, H L ; Reni, M ; Van Cutsem, E ; Macarulla Mercade, T ; Hall, M J ; Park, J O ; Hochhauser, D ; Arnold, D ; Oh, D-Y ; Reinacher-Schick, A ; Tortora, G ; Algül, H ; O’Reilly, E M ; McGuinness, D ; Cui, K Y ; Joo, S ; Yoo, H K ; Patel, N ; Golan, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-oup_primary_10_1093_annonc_mdz247_0033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hammel, P</creatorcontrib><creatorcontrib>Kindler, H L</creatorcontrib><creatorcontrib>Reni, M</creatorcontrib><creatorcontrib>Van Cutsem, E</creatorcontrib><creatorcontrib>Macarulla Mercade, T</creatorcontrib><creatorcontrib>Hall, M J</creatorcontrib><creatorcontrib>Park, J O</creatorcontrib><creatorcontrib>Hochhauser, D</creatorcontrib><creatorcontrib>Arnold, D</creatorcontrib><creatorcontrib>Oh, D-Y</creatorcontrib><creatorcontrib>Reinacher-Schick, A</creatorcontrib><creatorcontrib>Tortora, G</creatorcontrib><creatorcontrib>Algül, H</creatorcontrib><creatorcontrib>O’Reilly, E M</creatorcontrib><creatorcontrib>McGuinness, D</creatorcontrib><creatorcontrib>Cui, K Y</creatorcontrib><creatorcontrib>Joo, S</creatorcontrib><creatorcontrib>Yoo, H K</creatorcontrib><creatorcontrib>Patel, N</creatorcontrib><creatorcontrib>Golan, T</creatorcontrib><jtitle>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hammel, P</au><au>Kindler, H L</au><au>Reni, M</au><au>Van Cutsem, E</au><au>Macarulla Mercade, T</au><au>Hall, M J</au><au>Park, J O</au><au>Hochhauser, D</au><au>Arnold, D</au><au>Oh, D-Y</au><au>Reinacher-Schick, A</au><au>Tortora, G</au><au>Algül, H</au><au>O’Reilly, E M</au><au>McGuinness, D</au><au>Cui, K Y</au><au>Joo, S</au><au>Yoo, H K</au><au>Patel, N</au><au>Golan, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>675PDPOLO: Health-related quality of life (HRQoL) of olaparib maintenance treatment versus placebo in patients with a germline BRCA mutation and metastatic pancreatic cancer (mPC)</atitle><jtitle>Annals of oncology</jtitle><date>2019-10-01</date><risdate>2019</risdate><volume>30</volume><issue>Supplement_5</issue><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract><![CDATA[Abstract
Background
In the Phase III POLO trial (NCT02184195) patients (pts) with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and mPC derived a statistically significant and clinically meaningful progression-free survival benefit from maintenance olaparib compared with placebo. HRQoL assessment was a predefined secondary objective.
Methods
Pts with a gBRCAm and mPC whose disease had not progressed during first-line platinum-based chemotherapy were randomized to receive maintenance olaparib tablets (300 mg bid) or placebo. Pts completed the EORTC QLQ-C30 questionnaire at baseline and every 4 wks until discontinuation, with calculated scores ranging from 1–100. A change of ≥ 10 points was predefined as clinically meaningful improvement (increase) or deterioration (decrease) for global HRQoL and physical function score. Overall adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TCMD) was analysed using a log-rank test.
Results
Analyses were conducted in 89/92 olaparib pts and 58/62 placebo pts with evaluable baseline forms (overall compliance was 96.6% and 94.8%). There was no difference between arms for global HRQoL score (Table). The adjusted mean difference for physical function scale did not reach the threshold considered to be clinically meaningful. Global HRQoL and physical function remained relatively stable over time. There was no difference in TCMD for olaparib versus placebo for global HRQoL (median 21.2 vs 6.0 mo, respectively; hazard ratio 0.72 [95% CI 0.41–1.27]) or physical function (medians not reached, 1.38 [0.73–2.63]).
Table:675PDGlobal HRQoLPhysical functionMaintenance olaparibPlaceboMaintenance olaparibPlaceboAbsolute score, mean (n)Baseline70.4 (89)74.3 (58)83.3 (89)84.9 (58)Week 1273.6 (66)74.1 (36)84.4 (67)85.4 (36)Week 2473.4 (41)NC87.4 (43)NCWeek 4879.0 (23)NC89.6 (23)NCOverall change from baseline*Adjusted mean ± SE (n)−1.2±1.4 (84)1.3±1.9 (54)−2.1±1.3 (84)2.4± 1.7 (54)Between group difference (95% CI)−2.5 (−7.3, 2.3)−4.5 (−8.7, −0.2)P value0.310.04*Pts had to have baseline and ≥1 post-baseline assessmentNC, not calculated due to insufficient numbers of values; SE, standard error
Conclusions
HRQoL was preserved during maintenance olaparib treatment with no meaningful difference versus placebo. Findings support the observed clinical benefit of maintenance olaparib in pts with a gBRCAm and mPC.
Clinical trial identification
NCT02184195.
Editorial acknowledgement
Debbi Gorman, from Mudskipper Business, Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Legal entity responsible for the study
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Funding
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Disclosure
P. Hammel: Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution), Non-remunerated activity/ies: Erythec; Honoraria (self), Research grant / Funding (institution): Halozyme. H.L. Kindler: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Aldeyra Therapeutics; Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer-Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Erytech; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Ipsen Pharmaceuticals; Advisory / Consultancy: Kyowa; Advisory / Consultancy, Travel / Accommodation / Expenses: Paredox Therapeutics; Research grant / Funding (institution): Aduro; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Polaris; Research grant / Funding (institution): Verastem. M. Reni: Honoraria (self), Research grant / Funding (institution), Non-remunerated activity/ies: Celgene; Honoraria (self): Baxalta; Honoraria (self): Shire; Honoraria (self): Eli-Liily; Honoraria (self): Pfizer; Honoraria (self): Novocure; Honoraria (self): Novartis; Advisory / Consultancy, Steering committee member: AstraZeneca; Advisory / Consultancy, Steering committee member: Boston Pharmaceuticals. E. Van Cutsem: Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bristol-Myers Squibb. T. Macarulla Mercade: Advisory / Consultancy: Genzyme; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi Aventis; Advisory / Consultancy: Shire; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Baxalta; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Travel / Accommodation / Expenses: H3 Biomedicine; Advisory / Consultancy: QED Therapeutics; Research grant / Funding (institution): Agios pharmaceuticals, Aslan pharmaceuticals; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Halozyme, Inc, Immunomedics, Merrimack, Millennium; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis Farmaceutica S.A.; Research grant / Funding (institution): Novocure GmBH; Research grant / Funding (institution): Oncomed, Pharmacyclics; Research grant / Funding (institution): Pfizer S.L.U.; Travel / Accommodation / Expenses: Merck. M.J. Hall: Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: AstraZeneca; Travel / Accommodation / Expenses, Non-remunerated activity/ies, Non-remunerated activities relate to collaborative research: Caris Life Sciences; Non-remunerated activity/ies, Collaborative research: Myriad; Non-remunerated activity/ies, Collaborative research: Ambry; Non-remunerated activity/ies, Collaborative research: Invitae; Non-remunerated activity/ies, Collaborative research: Foundation Medicine; Non-remunerated activity/ies: Merck. J.O. Park: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Celgene; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Shire; Advisory / Consultancy: Merck; Advisory / Consultancy: Sereno. D. Arnold: Honoraria (self): AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Bayer; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self): Biocompatibles; Honoraria (self): Eli Lilly; Honoraria (self), Non-remunerated activity/ies: Merck Sharpe & Dohme; Honoraria (self), Non-remunerated activity/ies: Servier; Honoraria (self), Non-remunerated activity/ies: Sanofi; Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self): Terumo; Honoraria (self): Sirtex. D. Oh: Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech/ Roche; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Bayer; Advisory / Consultancy: Taiho; Advisory / Consultancy: Aslan; Advisory / Consultancy: Halozyme. A. Reinacher-Schick: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Baxalta; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Research grant / Funding (institution): Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Merck Sharpe & Dohme; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: Sanofi-Aventis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): AstraZeneca. G. Tortora: Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis. H. Algül: Honoraria (self): Celgene; Honoraria (self), Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): Chugai. E.M. O’Reilly: Advisory / Consultancy, Including spouse: 3DMedcare, Boston Scientific, CytomX, Daiichi, Debio, Delcath, Exelixis, Alignmed, An]]></abstract><pub>Oxford University Press</pub><doi>10.1093/annonc/mdz247.003</doi></addata></record> |
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| title | 675PDPOLO: Health-related quality of life (HRQoL) of olaparib maintenance treatment versus placebo in patients with a germline BRCA mutation and metastatic pancreatic cancer (mPC) |
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