dc.contributor.author | Tempero, M | |
dc.contributor.author | Oh, D-Y | |
dc.contributor.author | Tabernero, J | |
dc.contributor.author | Reni, M | |
dc.contributor.author | Van Cutsem, E | |
dc.contributor.author | Hendifar, A | |
dc.contributor.author | Waldschmidt, D-T | |
dc.contributor.author | Starling, N | |
dc.contributor.author | Bachet, J-B | |
dc.contributor.author | Chang, H-M | |
dc.contributor.author | Maurel, J | |
dc.contributor.author | Garcia-Carbonero, R | |
dc.contributor.author | Lonardi, S | |
dc.contributor.author | Coussens, LM | |
dc.contributor.author | Fong, L | |
dc.contributor.author | Tsao, LC | |
dc.contributor.author | Cole, G | |
dc.contributor.author | James, D | |
dc.contributor.author | Macarulla, T | |
dc.date.accessioned | 2021-07-29T10:37:03Z | |
dc.date.available | 2021-07-29T10:37:03Z | |
dc.identifier.citation | Annals of oncology : official journal of the European Society for Medical Oncology, 2021, 32 (5), pp. 600 - 608 | |
dc.identifier.issn | 0923-7534 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4714 | |
dc.identifier.eissn | 1569-8041 | |
dc.identifier.doi | 10.1016/j.annonc.2021.01.070 | |
dc.description.abstract | Background 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.format | Print-Electronic | |
dc.format.extent | 600 - 608 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Adenocarcinoma | |
dc.subject | Pancreatic Neoplasms | |
dc.subject | Paclitaxel | |
dc.subject | Piperidines | |
dc.subject | Adenine | |
dc.subject | Albumins | |
dc.subject | Deoxycytidine | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Treatment Outcome | |
dc.subject | Tumor Microenvironment | |
dc.title | Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-01-20 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.annonc.2021.01.070 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Annals of oncology : official journal of the European Society for Medical Oncology | |
pubs.issue | 5 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 32 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Gastrointestinal Cancers Clinical Trials | |
icr.researchteam | Gastrointestinal Cancers Clinical Trials | en_US |
dc.contributor.icrauthor | Starling, Naureen | |