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dc.contributor.authorBrahmer, JRen_US
dc.contributor.authorRodríguez-Abreu, Den_US
dc.contributor.authorRobinson, AGen_US
dc.contributor.authorHui, Ren_US
dc.contributor.authorCsőszi, Ten_US
dc.contributor.authorFülöp, Aen_US
dc.contributor.authorGottfried, Men_US
dc.contributor.authorPeled, Nen_US
dc.contributor.authorTafreshi, Aen_US
dc.contributor.authorCuffe, Sen_US
dc.contributor.authorO'Brien, Men_US
dc.contributor.authorRao, Sen_US
dc.contributor.authorHotta, Ken_US
dc.contributor.authorZhang, Jen_US
dc.contributor.authorLubiniecki, GMen_US
dc.contributor.authorDeitz, ACen_US
dc.contributor.authorRangwala, Ren_US
dc.contributor.authorReck, Men_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-02-16T10:48:12Z
dc.date.issued2017-12en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29129441en_US
dc.identifierS1470-2045(17)30690-3en_US
dc.identifier.citationLancet Oncol, 2017, 18 (12), pp. 1600 - 1609en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1188
dc.identifier.eissn1474-5488en_US
dc.identifier.doi10.1016/S1470-2045(17)30690-3en_US
dc.description.abstractBACKGROUND: In the phase 3 KEYNOTE-024 trial, treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive, advanced non-small-cell lung cancer (NSCLC) with a programmed cell death-ligand 1 (PD-L1) tumour proportion score of 50% or greater (PD-L1-positive). Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes (PROs). METHODS: In this multicentre, international, randomised, open-label, phase 3 trial, we recruited patients with treatment-naive, stage IV NSCLC in 102 sites in 16 countries. Eligible patients had measurable disease (per RECIST version 1.1) and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Patients were randomly assigned (1:1) via an interactive voice response system and integrated web response system to receive either pembrolizumab 200 mg every 3 weeks (35 cycles) or investigator-choice platinum-doublet chemotherapy (4-6 cycles or until documented disease progression or unacceptable toxicity). Randomisation was stratified according to geography, ECOG performance status, and histology. PROs were assessed at day 1 of cycles 1-3, every 9 weeks thereafter, at the treatment discontinuation visit, and at the 30-day safety assessment visit using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), the EORTC Quality of Life Questionnaire Lung Cancer 13 items (QLQ-LC13), and the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) questionnaire. The key exploratory PRO endpoints (analysed for all patients who received at least one dose of study treatment and completed at least one PRO instrument at at least one timepoint) were baseline-to-week-15 change in the QLQ-C30 global health status (GHS)/quality-of-life (QOL) score and time to deterioration of the composite of cough, chest pain, and dyspnoea in the QLQ-LC13. This study is registered with ClinicalTrials.gov, number NCT02142738, and is ongoing but no longer enrolling patients. FINDINGS: Between Sept 19, 2014, and Oct 29, 2015, 305 patients were randomly assigned to pembrolizumab (n=154) or chemotherapy (n=151). Three patients in each group did not complete any PRO instruments at any timepoints, and so 299 patients were included in the full analysis set. Of these patients, one in each group did not complete any PRO instruments before week 15, and so were not included in analyses of change from baseline to week 15. PRO compliance was greater than 90% at baseline and approximately 80% at week 15 for both groups. Least-squares mean baseline-to-week-15 change in QLQ-C30 GHS/QOL score was 6·9 (95% CI 3·3 to 10·6) for pembrolizumab and -0·9 (-4·8 to 3·0) for chemotherapy, for a difference of 7·8 (2·9 to 12·8; two-sided nominal p=0·0020). Fewer pembrolizumab-treated patients had deterioration in the QLQ-LC13 composite endpoint than did chemotherapy-treated patients (46 [31%] of 151 patients vs 58 [39%] of 148 patients). Time to deterioration was longer with pembrolizumab than with chemotherapy (median not reached [95% CI 8·5 to not reached] vs 5·0 months [3·6 to not reached]; hazard ratio 0·66, 95% CI 0·44-0·97; two-sided nominal p=0·029). INTERPRETATION: Pembrolizumab improves or maintains health-related QOL compared with that for chemotherapy, and might represent a new first-line standard of care for PD-L1-expressing, advanced NSCLC. FUNDING: Merck & Co.en_US
dc.format.extent1600 - 1609en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectAgeden_US
dc.subjectAntibodies, Monoclonal, Humanizeden_US
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen_US
dc.subjectB7-H1 Antigenen_US
dc.subjectCarcinoma, Non-Small-Cell Lungen_US
dc.subjectDose-Response Relationship, Drugen_US
dc.subjectDrug Administration Scheduleen_US
dc.subjectFemaleen_US
dc.subjectHumansen_US
dc.subjectInternationalityen_US
dc.subjectLung Neoplasmsen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectNeoplasm Invasivenessen_US
dc.subjectNeoplasm Stagingen_US
dc.subjectQuality of Lifeen_US
dc.subjectSurvival Analysisen_US
dc.subjectTreatment Outcomeen_US
dc.titleHealth-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-08-14en_US
rioxxterms.versionofrecord10.1016/S1470-2045(17)30690-3en_US
rioxxterms.licenseref.startdate2017-12en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfLancet Oncolen_US
pubs.issue12en_US
pubs.notesNot knownen_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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Treatment of thoracic tumours
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Treatment of thoracic tumours/Treatment of thoracic tumours (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume18en_US
pubs.embargo.termsNot knownen_US
icr.researchteamTreatment of thoracic tumoursen_US
dc.contributor.icrauthorO'Brien, Maryen_US
dc.contributor.icrauthorMarsden,en_US


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