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
Name:
KennedyOJ.pdf
Size:
962.6Kb
Format:
PDF
Description:
Identified with Open Access button
Authors
Kennedy, O. J.Kicinski, M.
Valpione, Sara
Gandini, S.
Suciu, S.
Blank, C. U.
Long, G. V.
Atkinson, V. G.
Dalle, S.
Haydon, A. M.
Meshcheryakov, A.
Khattak, A.
Carlino, M. S.
Sandhu, S.
Larkin, J.
Puig, S.
Ascierto, P. A.
Rutkowski, P.
Schadendorf, D.
Koornstra, R.
Hernandez-Aya, L.
Di Giacomo, A. M.
van den Eertwegh, A. J. M.
Grob, J. J.
Gutzmer, R.
Jamal, R.
van Akkooi, A. C. J.
Robert, C.
Eggermont, A. M. M.
Lorigan, Paul C
Mandala, M.
Affiliation
University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom. Electronic address: ojk@doctors.org.uk. EORTC Headquarters, Brussels, Belgium. Cancer Research UK Manchester Institute, Manchester and the Christie NHS Foundation Trust, Manchester, United Kingdom. Molecular and Pharmaco-Epidemiology Unit, European Institute of Oncology, IRCCS, Milano, Italy. Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, Netherlands. Melanoma Institute Australia, The University of Sydney, And Mater and Royal North Shore Hospitals, Sydney, NSW, Australia. Princess Alexandra Hospital, Brisbane, QLD, Australia. Hospices Civils de Lyon Cancer Institute, Lyon, France. Alfred Hospital, Melbourne, VIC, Australia. NN Blokhin Cancer Research Center, Moscow, Russian Federation. Fiona Stanley Hospital & Edith Cowan University, Perth, WA, Australia. Westmead and Blacktown Hospitals, Melanoma Institute Australia and the University of Sydney, Sydney, NSW, Australia. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Royal Marsden Hospital, London, United Kingdom. Hospital Clinic de Barcelona, Universitat de Barcelona, Spain &Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain. Istituto Nazionale Tumori IRCCS 'Fondazione G. Pascale', Naples, Italy. Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. University Hospital Essen, Essen and German Cancer Consortium, Heidelberg, Germany. Radboud University Medical Center Nijmegen, Nijmegen, Netherlands. Washington University School of Medicine, St. Louis, MO, USA. Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy. Amsterdam University Medical Center, Location VUMC, Amsterdam, Netherlands. Aix Marseille University, Hôpital de la Timone, Marseille, France. Skin Cancer Center, Hannover Medical School, Hannover, and Department of Dermatology, Johannes Wesling Klinikum Minden, Ruhr University Bochum, Minden, Germany. Centre Hospitalier de l'Université de Montréal (CHUM), Centre de recherche du CHUM, Montreal, QC, Canada. Gustave Roussy and Paris-Saclay University, Villejuif, France. Comprehensive Cancer Center Munich, Munich, Germany; Division of Cancer Sciences, University of Manchester and Christie NHS Foundation Trust, Manchester, United Kingdom. University of Perugia, Santa Maria Misericordia Hospital, Perugia, Italy. Princess Máxima Center and University Medical Center Utrecht, Utrecht, the Netherlands.Issue Date
2022
Metadata
Show full item recordAbstract
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.Citation
Kennedy OJ, Kicinski M, Valpione S, Gandini S, Suciu S, Blank CU, et al. 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 [Internet]. Vol. 165, European Journal of Cancer. Elsevier BV; 2022. p. 97–112.Journal
European Journal of CancerDOI
10.1016/j.ejca.2022.01.017PubMed ID
35220182Additional Links
https://dx.doi.org/10.1016/j.ejca.2022.01.017Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.ejca.2022.01.017
Scopus Count
Collections
Related articles
- Prognostic and predictive value of AJCC-8 staging in the phase III EORTC1325/KEYNOTE-054 trial of pembrolizumab vs placebo in resected high-risk stage III melanoma.
- Authors: Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon A, Lichinitser M, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJ, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, Lupinacci R, Krepler C, Ibrahim N, Kicinski M, Marreaud S, van Akkooi AC, Suciu S, Robert C
- Issue date: 2019 Jul
- Prognostic and predictive value of non-steroidal anti-inflammatory drugs in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.
- Authors: Kennedy OJ, Glassee N, Kicinski M, Blank CU, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Boers-Sonderen M, Giacomo AMD, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, van Akkooi ACJ, Gandini S, Buhrer E, Suciu S, Robert C, Eggermont AMM, Mandala M, Lorigan P, Valpione S
- Issue date: 2024 Apr
- Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial.
- Authors: Eggermont AMM, Blank CU, Mandalà M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C, EORTC Melanoma Group
- Issue date: 2021 May
- Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial.
- Authors: Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C
- Issue date: 2020 Nov 20
- Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial.
- Authors: Bottomley A, Coens C, Mierzynska J, Blank CU, Mandalà M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Puig S, Ascierto PA, Larkin J, Lorigan PC, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C, Eggermont AMM, EORTC Melanoma Group
- Issue date: 2021 May