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dc.contributor.authorTempero, M
dc.contributor.authorOh, D-Y
dc.contributor.authorTabernero, J
dc.contributor.authorReni, M
dc.contributor.authorVan Cutsem, E
dc.contributor.authorHendifar, A
dc.contributor.authorWaldschmidt, D-T
dc.contributor.authorStarling, N
dc.contributor.authorBachet, J-B
dc.contributor.authorChang, H-M
dc.contributor.authorMaurel, J
dc.contributor.authorGarcia-Carbonero, R
dc.contributor.authorLonardi, S
dc.contributor.authorCoussens, LM
dc.contributor.authorFong, L
dc.contributor.authorTsao, LC
dc.contributor.authorCole, G
dc.contributor.authorJames, D
dc.contributor.authorMacarulla, T
dc.date.accessioned2021-07-29T10:37:03Z
dc.date.available2021-07-29T10:37:03Z
dc.identifier.citationAnnals of oncology : official journal of the European Society for Medical Oncology, 2021, 32 (5), pp. 600 - 608
dc.identifier.issn0923-7534
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4714
dc.identifier.eissn1569-8041
dc.identifier.doi10.1016/j.annonc.2021.01.070
dc.description.abstractBackground First-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) includes nab-paclitaxel/gemcitabine. Ibrutinib, a Bruton's tyrosine kinase inhibitor, exhibits antitumor activity through tumor microenvironment modulation. The safety and efficacy of first-line ibrutinib plus nab-paclitaxel/gemcitabine treatment in patients with PDAC were evaluated.Patients and methods RESOLVE (NCT02436668) was a phase III, randomized, double-blind, placebo-controlled study. Patients (histologically-confirmed PDAC; stage IV diagnosis ≥6 weeks of randomization; Karnofsky performance score ≥70) were randomized to once-daily oral ibrutinib (560 mg) or placebo plus nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1000 mg/m 2 ). Primary endpoints were overall survival (OS) and investigator-assessed progression-free survival (PFS); overall response rate and safety were assessed.Results In total, 424 patients were randomized (ibrutinib arm, n = 211; placebo arm, n = 213). Baseline characteristics were balanced across arms. After a median follow-up of 25 months, there was no significant difference in OS between ibrutinib plus nab-paclitaxel/gemcitabine versus placebo plus nab-paclitaxel/gemcitabine (median of 9.7 versus 10.8 months; P = 0.3225). PFS was shorter for ibrutinib plus nab-paclitaxel/gemcitabine compared with placebo plus nab-paclitaxel/gemcitabine (median 5.3 versus 6.0 months; P < 0.0001). Overall response rates were 29% and 42%, respectively (P = 0.0058). Patients in the ibrutinib arm had less time on treatment and received lower cumulative doses for all agents compared with the placebo arm. The most common grade ≥3 adverse events for ibrutinib versus placebo arms included neutropenia (24% versus 35%), peripheral sensory neuropathy (17% versus 8%), and anemia (16% versus 17%). Primary reasons for any treatment discontinuation were disease progression and adverse events.Conclusions Ibrutinib plus nab-paclitaxel/gemcitabine did not improve OS or PFS for patients with PDAC. Safety was consistent with known profiles for these agents.
dc.formatPrint-Electronic
dc.format.extent600 - 608
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectAdenocarcinoma
dc.subjectPancreatic Neoplasms
dc.subjectPaclitaxel
dc.subjectPiperidines
dc.subjectAdenine
dc.subjectAlbumins
dc.subjectDeoxycytidine
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectTreatment Outcome
dc.subjectTumor Microenvironment
dc.titleIbrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study.
dc.typeJournal Article
dcterms.dateAccepted2021-01-20
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.annonc.2021.01.070
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfAnnals of oncology : official journal of the European Society for Medical Oncology
pubs.issue5
pubs.notesNot known
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume32
pubs.embargo.termsNot known
icr.researchteamGastrointestinal Cancers Clinical Trials
icr.researchteamGastrointestinal Cancers Clinical Trialsen_US
dc.contributor.icrauthorStarling, Naureenen


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