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High serum sodium predicts immunotherapy response in metastatic renal cell and urothelial carcinoma.
Klümper, Niklas; Cox, Alexander; Eckstein, Markus; Kuppe, Christoph; Ritter, Manuel; Brossart, Peter; Luetkens, Julian; Hölzel, Michael; Stein, Johannes; Saal, Jonas.
Afiliação
  • Klümper N; Department of Urology, University Hospital Bonn (UKB), Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Germany; Institute of Experimental Oncology, University Hospital Bonn (UKB), Bonn, Germany.
  • Cox A; Department of Urology, University Hospital Bonn (UKB), Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Germany.
  • Eckstein M; Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Comprehensive Cancer Center EMN, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Bavarian Center for Cancer Research (
  • Kuppe C; Department of Nephrology, Rheumatology, and Clinical Immunology, University Hospital RWTH Aachen, Aachen, Germany.
  • Ritter M; Department of Urology, University Hospital Bonn (UKB), Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Germany.
  • Brossart P; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Germany; Medical Clinic III for Oncology, Hematology, Immune-Oncology and Rheumatology, University Hospital Bonn (UKB), Germany.
  • Luetkens J; Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany; Quantitative Imaging Lab Bonn (QILaB), Bonn, Germany.
  • Hölzel M; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Germany; Institute of Experimental Oncology, University Hospital Bonn (UKB), Bonn, Germany.
  • Stein J; Department of Urology, University Hospital Bonn (UKB), Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Germany.
  • Saal J; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Germany; Department of Nephrology, Rheumatology, and Clinical Immunology, University Hospital RWTH Aachen, Aachen, Germany; Medical Clinic III for Oncology, Hematology, Immune-Oncology and Rheumatology, University Hospital Bon
Eur J Cancer ; 204: 114089, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38703618
ABSTRACT

OBJECTIVES:

The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending.

METHODS:

We conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib. This analysis aimed to evaluate the prognostic and predictive value of these electrolyte levels in these clinical settings. A total of 1787 patients (IMvigor211 n = 901; IMmotion151 n = 886) were analyzed.

RESULTS:

We found a linear correlation of baseline serum sodium and chloride with prognosis across both trials, which was not found for potassium, magnesium and calcium. In multivariate analysis, the prognostic capacity of sodium was limited to patients receiving ICI as compared to the control group. Interestingly, in both studies, the chance of achieving an objective response was highest in the patient subgroup with high baseline serum sodium levels of > 140 mmol/L (IMmotion151 Complete response in 17.9% versus 2.0% in patients with mRCC with baseline sodium < 135 mmol/L). Serum sodium outperformed tumor PD-L1 expression as a predictor for immunotherapy efficacy.

CONCLUSIONS:

Patients exhibiting elevated serum sodium levels derive the greatest benefit from immunotherapy, suggesting that baseline serum concentration could serve as a valuable and cost-effective predictive biomarker for immunotherapy across entities.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sódio / Carcinoma de Células Renais / Neoplasias Renais Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sódio / Carcinoma de Células Renais / Neoplasias Renais Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article