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

• DOI: 10.1016/j.ejca.2022.01.017
• Publication Date: 2022-02-24T13:25:35Z
• Authors: Oliver J. Kennedy; Michal Kicinski; Sara Valpione; Sara Gandini; Stefan Suciu; Christian U. Blank; Georgina V. Long; Victoria G. Atkinson; Stéphane Dalle; Andrew M. Haydon; Andrey Meshcheryakov; Adnan Khattak; Matteo S. Carlino; Shahneen Sandhu; James Larkin; Susana Puig; Paolo A. Ascierto; Piotr Rutkowski; Dirk Schadendorf; Rutger Koornstra; Leonel Hernandez-Aya; Anna M. Di Giacomo; Alfonsus J.M. van...; Jean-Jacques Grob; Ralf Gutzmer; Rahima Jamal; Alexander C.J. va...; Caroline Robert; Alexander M.M. Eg...; Paul Lorigan; Mario Mandala
• Keywords: Skin Neoplasms; Prognosi; Adrenergic beta-Antagonists; Medizin; 610; Radboud University Medical Center; Diseases; immunomodulation; Antibodies, Monoclonal, Humanized; Adrenergic beta-antagonists; Beta-blockers; Immunomodulation; Immunotherapy; Melanoma; Adjuvants, Immunologic; Adrenergic beta-Antagonists; Antibodies, Monoclonal, Humanized; Humans; Neoplasm Staging; Prognosis; Tumor Microenvironment; Melanoma; Skin Neoplasms; Antibodies; Immunomodulation; Beta-blockers; beta-blockers; 03 medical and health sciences; Radboudumc 2: Cancer development and immune defence RIHS: Radboud Institute for Health Sciences; Melanoma, Cutaneous Malignant; 0302 clinical medicine; Adjuvants, Immunologic; Immunologic; Monoclonal; 616; Medicine and Health Sciences; melanoma; Tumor Microenvironment; Adrenergic beta-antagonists; Humans; Clinical Trials; Beta-blocker; Adjuvants; Humanized; adrenergic beta-antagonists; Melanoma; Neoplasm Staging; Prognosis; ResearchInstitutes_Networks_Beacons/mcrc; name=Manchester Cancer Research Centre; 3. Good health; Adrenergic beta-antagonist; Immunotherapy; immunotherapy; Human

β-adrenergic receptors are upregulated in melanoma cells and contribute to an immunosuppressive, pro-tumorigenic microenvironment. This study investigated the prognostic predictive value of β-adrenoreceptor blockade by β-blockers EORTC1325/KEYNOTE-054 randomised controlled trial.Patients with resected stage IIIA, IIIB or IIIC regional lymphadenectomy received 200 mg adjuvant pembrolizumab (n = 514) placebo 505) every three weeks for one year until recurrence unacceptable toxicity. At a median follow-up 3 years, prolonged recurrence-free survival (RFS) compared (hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.47-0.68). β-blocker use was defined as oral administration any within 30 days randomisation. A multivariable Cox proportional hazard model used estimate HR association between RFS.Ninety-nine (10%) 1019 patients at baseline. had no independent effect on RFS: 0.96 (95% CI 0.70-1.31). The HRs RFS associated were 0.67 0.38-1.19) arm 1.15 0.80-1.66) arm. 0.34 0.18-0.65) among users 0.59 0.48-0.71) those not using β-blockers.This suggests high-risk III melanoma. However, may predict improved efficacy treatment. combination immunotherapy merits further investigation. is registered ClinicalTrials.gov, NCT02362594, EudraCT, 2014-004944-37.