Thrombospondin‐2 and ldh are putative predictive biomarkers for treatment with everolimus in second‐line metastatic clear cell renal cell carcinoma (Marc‐2 study)

Zeuschner P, Hölters S, Stöckle M, Seliger B, Mueller A, Bachmann HS, Grünwald V, Christoph DC, Stenzl A, Grimm MO, Brüning F, Goebell P, Augustin M, Roos F, Harde J, Benz‐rüd I, Staehler M, Junker K (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cancers MDPI

Book Volume: 13

Article Number: 2594

Journal Issue: 11

DOI: 10.3390/cancers13112594

Abstract

There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC‐2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second‐line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis‐related protein thrombospondin‐2 (TSP‐2) at baseline (≤ 665 parts per billion, ppb) identified therapy responders with longer median progression‐free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, p = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, p = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, p < 0.001). Baseline TSP‐2 levels had a stronger relation to PFS (HR 0.36, p = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, p < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP‐2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF‐targeted therapy in patients with clear cell mRCC.

Authors with CRIS profile

Peter Goebell Urologische Klinik

Involved external institutions

Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Martin-Luther-Universität Halle-Wittenberg (MLU) DE Germany (DE) Universität Witten/Herdecke DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Universitätsklinikum Jena DE Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) DE Germany (DE) Paracelsus Medizinische Privatuniversität, Nürnberg DE Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) iOMEDICO AG DE Germany (DE) Klinikum der Universität München DE Germany (DE)

How to cite

APA:

Zeuschner, P., Hölters, S., Stöckle, M., Seliger, B., Mueller, A., Bachmann, H.S.,... Junker, K. (2021). Thrombospondin‐2 and ldh are putative predictive biomarkers for treatment with everolimus in second‐line metastatic clear cell renal cell carcinoma (Marc‐2 study). Cancers, 13(11). https://doi.org/10.3390/cancers13112594

MLA:

Zeuschner, Philip, et al. "Thrombospondin‐2 and ldh are putative predictive biomarkers for treatment with everolimus in second‐line metastatic clear cell renal cell carcinoma (Marc‐2 study)." Cancers 13.11 (2021).

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