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dc.contributor.authorLong, GV
dc.contributor.authorWeber, JS
dc.contributor.authorLarkin, J
dc.contributor.authorAtkinson, V
dc.contributor.authorGrob, J-J
dc.contributor.authorSchadendorf, D
dc.contributor.authorDummer, R
dc.contributor.authorRobert, C
dc.contributor.authorMárquez-Rodas, I
dc.contributor.authorMcNeil, C
dc.contributor.authorSchmidt, H
dc.contributor.authorBriscoe, K
dc.contributor.authorBaurain, J-F
dc.contributor.authorHodi, FS
dc.contributor.authorWolchok, JD
dc.date.accessioned2018-02-14T10:18:25Z
dc.date.issued2017-11
dc.identifier.citationJAMA oncology, 2017, 3 (11), pp. 1511 - 1519
dc.identifier.issn2374-2437
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1064
dc.identifier.eissn2374-2445
dc.identifier.doi10.1001/jamaoncol.2017.1588
dc.description.abstractImportance Immune checkpoint inhibitors have demonstrated atypical response patterns, which may not be fully captured by conventional response criteria. There is a need to better understand the potential benefit of continued immune checkpoint inhibition beyond progression.Objective To evaluate the safety and potential benefit of nivolumab (anti-programmed cell death receptor 1) monotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression.Design, setting, and participants Pooled, retrospective analysis of data from phase 3 trials of nivolumab in treatment-naive patients with advanced melanoma (CheckMate 066 or CheckMate 067) conducted at academic and clinical cancer centers. Participants were patients treated beyond first disease progression, defined as those who received their last dose of nivolumab more than 6 weeks after progression (TBP group); and patients not treated beyond progression, who discontinued nivolumab therapy before or at progression (non-TBP group). Data analyses were conducted from November 6, 2015, to January 11, 2017.Interventions Nivolumab (3 mg/kg every 2 weeks) administered until progression or unacceptable toxic effects. Patients could be treated beyond progression if deriving apparent clinical benefit and tolerating study drug, at the investigator's discretion.Main outcomes and measures Tumor response and safety in TBP and non-TBP patients.Results Among 526 randomized patients (39% [n = 203] female; median age, 62 years [range, 18-90 years]), 306 (58%) experienced disease progression, including 85 (28%) TBP patients and 221 (72%) non-TBP patients. Twenty-four (28%) of the TBP patients had a target lesion reduction of greater than 30% after progression compared with baseline (TBP>30% group). At the time of this analysis, 65 (76%) TBP patients and 21 (87%) TBP>30% patients were still alive; 27 (32%) and 11 (46%), respectively, continued to receive treatment. Median (range) time from progression to last dose of treatment was 4.7 (1.4-25.8) months for TBP patients and 7.6 (2.4-19.4) months for TBP>30% patients. Median (range) time from progression to greater than 30% tumor reduction was 1.4 (0.2-7.0) months. Treatment-related select grade 3 to 4 adverse events were similar in the TBP and non-TBP groups (5 [6%] and 9 [4%], respectively).Conclusions and relevance A substantial proportion of selected patients treated with frontline nivolumab who were clinically stable and judged to be eligible for treatment beyond RECIST v1.1-defined progression by the treating investigators derived apparent clinical benefit without compromising safety. Further analysis will help define the potential benefit of continued nivolumab treatment beyond progression.Trial registration clinicaltrials.gov Identifiers: NCT01721772 (CheckMate 066) and NCT01844505 (CheckMate 067).
dc.formatPrint
dc.format.extent1511 - 1519
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectMelanoma
dc.subjectSkin Neoplasms
dc.subjectDisease Progression
dc.subjectAntibodies, Monoclonal
dc.subjectDisease-Free Survival
dc.subjectTreatment Outcome
dc.subjectDrug Administration Schedule
dc.subjectRisk Factors
dc.subjectRetrospective Studies
dc.subjectTime Factors
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectClinical Trials, Phase III as Topic
dc.subjectYoung Adult
dc.subjectKaplan-Meier Estimate
dc.subjectAntineoplastic Agents, Immunological
dc.subjectNivolumab
dc.titleNivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials.
dc.typeJournal Article
rioxxterms.versionofrecord10.1001/jamaoncol.2017.1588
rioxxterms.licenseref.startdate2017-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJAMA oncology
pubs.issue11
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/Melanoma and Kidney Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (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/Melanoma and Kidney Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume3
pubs.embargo.termsNot known
icr.researchteamMelanoma and Kidney Canceren_US
dc.contributor.icrauthorLarkin, Jamesen
dc.contributor.icrauthorMarsden,en


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