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dc.contributor.authorRafii, Sen_US
dc.contributor.authorGourley, Cen_US
dc.contributor.authorKumar, Ren_US
dc.contributor.authorGeuna, Een_US
dc.contributor.authorErn Ang, Jen_US
dc.contributor.authorRye, Ten_US
dc.contributor.authorChen, L-Men_US
dc.contributor.authorShapira-Frommer, Ren_US
dc.contributor.authorFriedlander, Men_US
dc.contributor.authorMatulonis, Uen_US
dc.contributor.authorDe Greve, Jen_US
dc.contributor.authorOza, AMen_US
dc.contributor.authorBanerjee, Sen_US
dc.contributor.authorMolife, LRen_US
dc.contributor.authorGore, MEen_US
dc.contributor.authorKaye, SBen_US
dc.contributor.authorYap, TAen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2017-05-26T15:37:33Z
dc.date.issued2017-07-18en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28454085en_US
dc.identifier17005en_US
dc.identifier.citationOncotarget, 2017, 8 (29), pp. 47154 - 47160en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/665
dc.identifier.eissn1949-2553en_US
dc.identifier.doi10.18632/oncotarget.17005en_US
dc.description.abstractBACKGROUND: The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. RESULTS: 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. METHODS: We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. CONCLUSION: PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.en_US
dc.format.extent47154 - 47160en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectBRCAen_US
dc.subjectPARP inhibitoren_US
dc.subjectolapariben_US
dc.subjectovarian canceren_US
dc.subjectpredictive biomarkersen_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectBRCA1 Proteinen_US
dc.subjectBRCA2 Proteinen_US
dc.subjectFemaleen_US
dc.subjectGerm-Line Mutationen_US
dc.subjectHumansen_US
dc.subjectMiddle Ageden_US
dc.subjectNeoplasm Gradingen_US
dc.subjectNeoplasm Metastasisen_US
dc.subjectNeoplasm Stagingen_US
dc.subjectOvarian Neoplasmsen_US
dc.subjectPhthalazinesen_US
dc.subjectPiperazinesen_US
dc.subjectPoly(ADP-ribose) Polymerase Inhibitorsen_US
dc.subjectPrognosisen_US
dc.subjectRecurrenceen_US
dc.subjectSurvival Analysisen_US
dc.subjectTreatment Outcomeen_US
dc.titleBaseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-02-22en_US
rioxxterms.versionofrecord10.18632/oncotarget.17005en_US
rioxxterms.licenseref.startdate2017-07-18en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfOncotargeten_US
pubs.issue29en_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine Drug Development Unit (Kaye)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume8en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamMedicine Drug Development Unit (de Bono)en_US
icr.researchteamMedicine Drug Development Unit (Kaye)en_US
dc.contributor.icrauthorYap, Timothyen_US
dc.contributor.icrauthorGore, Martinen_US
dc.contributor.icrauthorBanerjee, Susanaen_US
dc.contributor.icrauthorMolife, Rhodaen_US
dc.contributor.icrauthorMarsden,en_US
dc.contributor.icrauthorKaye, Stanley Bernarden_US


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