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dc.contributor.authorHarrington, KJen_US
dc.contributor.authorFerris, RLen_US
dc.contributor.authorBlumenschein, Gen_US
dc.contributor.authorColevas, ADen_US
dc.contributor.authorFayette, Jen_US
dc.contributor.authorLicitra, Len_US
dc.contributor.authorKasper, Sen_US
dc.contributor.authorEven, Cen_US
dc.contributor.authorVokes, EEen_US
dc.contributor.authorWorden, Fen_US
dc.contributor.authorSaba, NFen_US
dc.contributor.authorKiyota, Nen_US
dc.contributor.authorHaddad, Ren_US
dc.contributor.authorTahara, Men_US
dc.contributor.authorGrünwald, Ven_US
dc.contributor.authorShaw, JWen_US
dc.contributor.authorMonga, Men_US
dc.contributor.authorLynch, Men_US
dc.contributor.authorTaylor, Fen_US
dc.contributor.authorDeRosa, Men_US
dc.contributor.authorMorrissey, Len_US
dc.contributor.authorCocks, Ken_US
dc.contributor.authorGillison, MLen_US
dc.contributor.authorGuigay, Jen_US
dc.date.accessioned2017-08-02T09:28:16Z
dc.date.issued2017-08en_US
dc.identifier.citationThe Lancet. Oncology, 2017, 18 (8), pp. 1104 - 1115en_US
dc.identifier.issn1470-2045en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/751
dc.identifier.eissn1474-5488en_US
dc.identifier.doi10.1016/s1470-2045(17)30421-7en_US
dc.description.abstractBACKGROUND:Patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options and poor prognosis. Nivolumab significantly improved survival of this patient population when compared with standard single-agent therapy of investigator's choice in Checkmate 141; here we report the effect of nivolumab on patient-reported outcomes (PROs). METHODS:CheckMate 141 was a randomised, open-label, phase 3 trial in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who progressed within 6 months after platinum-based chemotherapy. Patients were randomly assigned (2:1) to nivolumab 3 mg/kg every 2 weeks (n=240) or investigator's choice (n=121) of methotrexate (40-60 mg/m2 of body surface area), docetaxel (30-40 mg/m2), or cetuximab (250 mg/m2 after a loading dose of 400 mg/m2) until disease progression, intolerable toxicity, or withdrawal of consent. On Jan 26, 2016, the independent data monitoring committee reviewed the data at the planned interim analysis and declared overall survival superiority for nivolumab over investigator's choice therapy (primary endpoint; described previously). The protocol was amended to allow patients in the investigator's choice group to cross over to nivolumab. All patients not on active therapy are being followed for survival. As an exploratory endpoint, PROs were assessed at baseline, week 9, and every 6 weeks thereafter using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30), the EORTC head and neck cancer-specific module (EORTC QLQ-H&N35), and the three-level European Quality of Life-5 Dimensions (EQ-5D) questionnaire. Differences within and between treatment groups in PROs were analysed by ANCOVA among patients with baseline and at least one other assessment. All randomised patients were included in the time to clinically meaningful deterioration analyses. Median time to clinically meaningful deterioration was analysed by Kaplan-Meier methods. CheckMate 141 was registered with ClinicalTrials.org, number NCT02105636. FINDINGS:Patients were enrolled between May 29, 2014, and July 31, 2015, and subsequently 361 patients were randomly assigned to receive nivolumab (n=240) or investigator's choice (n=121). Among them, 129 patients (93 in the nivolumab group and 36 in the investigator's choice group) completed any of the PRO questionnaires at baseline and at least one other assessment. Treatment with nivolumab resulted in adjusted mean changes from baseline to week 15 ranging from -2·1 to 5·4 across functional and symptom domains measured by the EORTC QLQ-C30, with no domains indicating clinically meaningful deterioration. By contrast, eight (53%) of the 15 domains in the investigator's choice group showed clinically meaningful deterioration (10 points or more) at week 15 (change from baseline range, -24·5 to 2·4). Similarly, on the EORTC QLQ-H&N35, clinically meaningful worsening at week 15 was seen in no domains in the nivolumab group and eight (44%) of 18 domains in the investigator's choice group. Patients in the nivolumab group had a clinically meaningful improvement (according to a difference of 7 points or greater) in adjusted mean change from baseline to week 15 on the EQ-5D visual analogue scale, in contrast to a clinically meaningful deterioration in the investigator's choice group (7·3 vs -7·8). Differences between groups were significant and clinically meaningful at weeks 9 and 15 in favour of nivolumab for role functioning, social functioning, fatigue, dyspnoea, and appetite loss on the EORTC QLQ-C30 and pain and sensory problems on the EORTC QLQ-H&N35. Median time to deterioration was significantly longer with nivolumab versus investigator's choice for 13 (37%) of 35 domains assessed across the three questionnaires. INTERPRETATION:In this exploratory analysis of CheckMate 141, nivolumab stabilised symptoms and functioning from baseline to weeks 9 and 15, whereas investigator's choice led to clinically meaningful deterioration. Nivolumab delayed time to deterioration of patient-reported quality-of-life outcomes compared with single-agent therapy of investigator's choice in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck. In view of the major unmet need in this population and the importance of maintaining or improving quality of life for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, these data support nivolumab as a new standard-of-care option in this setting. FUNDING:Bristol-Myers Squibb.en_US
dc.formatPrint-Electronicen_US
dc.format.extent1104 - 1115en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectHumansen_US
dc.subjectCarcinoma, Squamous Cellen_US
dc.subjectHead and Neck Neoplasmsen_US
dc.subjectNeoplasm Recurrence, Localen_US
dc.subjectDyspneaen_US
dc.subjectPainen_US
dc.subjectSensation Disordersen_US
dc.subjectDisease Progressionen_US
dc.subjectFatigueen_US
dc.subjectAnorexiaen_US
dc.subjectTaxoidsen_US
dc.subjectMethotrexateen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectAntibodies, Monoclonalen_US
dc.subjectQuality of Lifeen_US
dc.subjectKaplan-Meier Estimateen_US
dc.subjectSocial Participationen_US
dc.subjectCetuximaben_US
dc.subjectPatient Reported Outcome Measuresen_US
dc.subjectDocetaxelen_US
dc.subjectNivolumaben_US
dc.titleNivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-05-12en_US
rioxxterms.versionofrecord10.1016/s1470-2045(17)30421-7en_US
rioxxterms.licenseref.startdate2017-08en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfThe Lancet. Oncologyen_US
pubs.issue8en_US
pubs.notes12 monthsen_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 Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume18en_US
pubs.embargo.terms12 monthsen_US
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorHarrington, Kevinen_US
dc.contributor.icrauthorMarsden,en_US


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