Show simple item record

dc.contributor.authorKennedy, OJ
dc.contributor.authorKicinski, M
dc.contributor.authorValpione, S
dc.contributor.authorGandini, S
dc.contributor.authorSuciu, S
dc.contributor.authorBlank, CU
dc.contributor.authorLong, GV
dc.contributor.authorAtkinson, VG
dc.contributor.authorDalle, S
dc.contributor.authorHaydon, AM
dc.contributor.authorMeshcheryakov, A
dc.contributor.authorKhattak, A
dc.contributor.authorCarlino, MS
dc.contributor.authorSandhu, S
dc.contributor.authorLarkin, J
dc.contributor.authorPuig, S
dc.contributor.authorAscierto, PA
dc.contributor.authorRutkowski, P
dc.contributor.authorSchadendorf, D
dc.contributor.authorKoornstra, R
dc.contributor.authorHernandez-Aya, L
dc.contributor.authorDi Giacomo, AM
dc.contributor.authorvan den Eertwegh, AJM
dc.contributor.authorGrob, J-J
dc.contributor.authorGutzmer, R
dc.contributor.authorJamal, R
dc.contributor.authorvan Akkooi, ACJ
dc.contributor.authorRobert, C
dc.contributor.authorEggermont, AMM
dc.contributor.authorLorigan, P
dc.contributor.authorMandala, M
dc.coverage.spatialEngland
dc.date.accessioned2022-08-26T10:39:25Z
dc.date.available2022-08-26T10:39:25Z
dc.date.issued2022-04-01
dc.identifierS0959-8049(22)00038-7
dc.identifier.citationEuropean Journal of Cancer, 2022, 165 pp. 97 - 112en_US
dc.identifier.issn0959-8049
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5333
dc.identifier.eissn1879-0852
dc.identifier.eissn1879-0852
dc.identifier.doi10.1016/j.ejca.2022.01.017
dc.description.abstractBACKGROUND: β-adrenergic receptors are upregulated in melanoma cells and contribute to an immunosuppressive, pro-tumorigenic microenvironment. This study investigated the prognostic and predictive value of β-adrenoreceptor blockade by β-blockers in the EORTC1325/KEYNOTE-054 randomised controlled trial. METHODS: Patients with resected stage IIIA, IIIB or IIIC melanoma and regional lymphadenectomy received 200 mg of adjuvant pembrolizumab (n = 514) or placebo (n = 505) every three weeks for one year or until recurrence or unacceptable toxicity. At a median follow-up of 3 years, pembrolizumab prolonged recurrence-free survival (RFS) compared to placebo (hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.47-0.68). β-blocker use was defined as oral administration of any β-blocker within 30 days of randomisation. A multivariable Cox proportional hazard model was used to estimate the HR for the association between the use of β-blockers and RFS. RESULTS: Ninety-nine (10%) of 1019 randomised patients used β-blockers at baseline. β-blockers had no independent prognostic effect on RFS: HR 0.96 (95% CI 0.70-1.31). The HRs of RFS associated with β-blocker use were 0.67 (95% CI 0.38-1.19) in the pembrolizumab arm and 1.15 (95% CI 0.80-1.66) in the placebo arm. The HR of RFS associated with pembrolizumab compared to placebo was 0.34 (95% CI 0.18-0.65) among β-blocker users and 0.59 (95% CI 0.48-0.71) among those not using β-blockers. CONCLUSIONS: This study suggests no prognostic effect of β-blockers in resected high-risk stage III melanoma. However, β-blockers may predict improved efficacy of adjuvant pembrolizumab treatment. The combination of immunotherapy with β-blockers merits further investigation. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37.
dc.formatPrint-Electronic
dc.format.extent97 - 112
dc.languageeng
dc.language.isoengen_US
dc.publisherELSEVIER SCI LTDen_US
dc.relation.ispartofEuropean Journal of Cancer
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectAdrenergic beta-antagonists
dc.subjectBeta-blockers
dc.subjectImmunomodulation
dc.subjectImmunotherapy
dc.subjectMelanoma
dc.subjectAdjuvants, Immunologic
dc.subjectAdrenergic beta-Antagonists
dc.subjectAntibodies, Monoclonal, Humanized
dc.subjectHumans
dc.subjectMelanoma
dc.subjectNeoplasm Staging
dc.subjectPrognosis
dc.subjectSkin Neoplasms
dc.subjectTumor Microenvironment
dc.titlePrognostic and predictive value of β-blockers in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-01-28
dc.date.updated2022-08-26T10:38:55Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1016/j.ejca.2022.01.017en_US
rioxxterms.licenseref.startdate2022-04-01
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35220182
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/Royal Marsden Clinical Units
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.)
pubs.publication-statusPublished
pubs.volume165
dc.contributor.icrauthorLarkin, James
icr.provenanceDeposited by Mr Arek Surman on 2022-08-26. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S0959804922000387-main.pdf


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by-nc-nd/4.0/
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/