dc.contributor.author | Kennedy, OJ | |
dc.contributor.author | Kicinski, M | |
dc.contributor.author | Valpione, S | |
dc.contributor.author | Gandini, S | |
dc.contributor.author | Suciu, S | |
dc.contributor.author | Blank, CU | |
dc.contributor.author | Long, GV | |
dc.contributor.author | Atkinson, VG | |
dc.contributor.author | Dalle, S | |
dc.contributor.author | Haydon, AM | |
dc.contributor.author | Meshcheryakov, A | |
dc.contributor.author | Khattak, A | |
dc.contributor.author | Carlino, MS | |
dc.contributor.author | Sandhu, S | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Puig, S | |
dc.contributor.author | Ascierto, PA | |
dc.contributor.author | Rutkowski, P | |
dc.contributor.author | Schadendorf, D | |
dc.contributor.author | Koornstra, R | |
dc.contributor.author | Hernandez-Aya, L | |
dc.contributor.author | Di Giacomo, AM | |
dc.contributor.author | van den Eertwegh, AJM | |
dc.contributor.author | Grob, J-J | |
dc.contributor.author | Gutzmer, R | |
dc.contributor.author | Jamal, R | |
dc.contributor.author | van Akkooi, ACJ | |
dc.contributor.author | Robert, C | |
dc.contributor.author | Eggermont, AMM | |
dc.contributor.author | Lorigan, P | |
dc.contributor.author | Mandala, M | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-08-26T10:39:25Z | |
dc.date.available | 2022-08-26T10:39:25Z | |
dc.date.issued | 2022-04-01 | |
dc.identifier | S0959-8049(22)00038-7 | |
dc.identifier.citation | European Journal of Cancer, 2022, 165 pp. 97 - 112 | en_US |
dc.identifier.issn | 0959-8049 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5333 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.doi | 10.1016/j.ejca.2022.01.017 | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 97 - 112 | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | ELSEVIER SCI LTD | en_US |
dc.relation.ispartof | European Journal of Cancer | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | Adrenergic beta-antagonists | |
dc.subject | Beta-blockers | |
dc.subject | Immunomodulation | |
dc.subject | Immunotherapy | |
dc.subject | Melanoma | |
dc.subject | Adjuvants, Immunologic | |
dc.subject | Adrenergic beta-Antagonists | |
dc.subject | Antibodies, Monoclonal, Humanized | |
dc.subject | Humans | |
dc.subject | Melanoma | |
dc.subject | Neoplasm Staging | |
dc.subject | Prognosis | |
dc.subject | Skin Neoplasms | |
dc.subject | Tumor Microenvironment | |
dc.title | Prognostic 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.type | Journal Article | |
dcterms.dateAccepted | 2022-01-28 | |
dc.date.updated | 2022-08-26T10:38:55Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1016/j.ejca.2022.01.017 | en_US |
rioxxterms.licenseref.startdate | 2022-04-01 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://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-status | Published | |
pubs.volume | 165 | |
dc.contributor.icrauthor | Larkin, James | |
icr.provenance | Deposited by Mr Arek Surman on 2022-08-26. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S0959804922000387-main.pdf | |