Improved survival of advanced melanoma patients receiving immunotherapy with concomitant antithrombotic therapy - A multicenter study on 2419 patients from the prospective skin cancer registry ADOReg.

Kött J, Zell T, Zimmermann N, Rünger A, Smit DJ, Abeck F, Geidel G, Hansen-Abeck I, Heidrich I, Weichenthal M, Ugurel S, Leiter U, Berking C, Gutzmer R, Schadendorf D, Zimmer L, Livingstone E, Wasielewski Iv, Mohr P, Meier F, Haferkamp S, Drexler K, Herbst R, Kellner I, Utikal J, Wohlfeil SA, Pföhler C, Adam L, Terheyden P, Ulrich J, Meiss F, Möbes M, Welzel J, Schilling B, Ziller F, Kaatz M, Kreuter A, Sindrilaru A, Dippel E, Sachse M, Weishaupt C, Hüning S, Heinzerling L, Loquai C, Schley G, Gambichler T, Löffler H, Grabbe S, Schultz E, Devereux N, Hassel JC, Simon JC, Raap U, Assaf C, Klemke CD, Sunderkötter C, Hofmann SC, Wenk S, Tronnier M, Thies S, Heppt M, Eggermont A, Schulze HJ, Zouboulis CC, Tüting T, Bauer AT, Schneider SW, Gebhardt C (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 214

DOI: 10.1016/j.ejca.2024.115159

Abstract

BACKGROUND: Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis. Preclinical studies indicate a beneficial effect, clinical data has been inconsistent. METHODS: We examined a cohort of advanced, non-resectable melanoma patients (n = 2419) derived from the German prospective multicenter skin cancer registry ADOReg, who were treated with immune checkpoint inhibitors (ICI). The patients were classified based on whether it was documented that they received platelet aggregation inhibition (PAI) (n = 137) (acetylsalicylic acid (ASA) or clopidogrel), anticoagulation (AC) (n = 185) (direct oral anticoagulation (DOAC), phenprocoumon, heparins) at the start of ICI or no antithrombotic medication (n = 2097) at any point during ICI treatment. The study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). RESULTS: A significantly improved PFS was observed in patients documented to receive ASA (15.1 vs 6.4 months, HR 0.67, 95 % CI: 0.5 to 0.88, p = 0.0047) as well as in patients to receive AC (15.1 vs. 6.4 months, HR 0.7, 95 % CI: 0.53 to 0.91, p = 0.01) compared to patients for whom no antithrombotic medication was documented. Multivariate analysis of OS showed significant risk reduction in patients who received DOAC (HR 0.68, 95 % CI: 0.49 to 0.92, p = 0.0170) or phenprocoumon (HR: 0.44, 95 % CI: 0.19 to 0.85, p = 0.0301). CONCLUSION: Our study indicates a positive prognostic effect of anticoagulant and antiplatelet concomitant medication in melanoma patients receiving ICI. Further studies are needed to confrim the cancer-related benefit of adding anticoagulation or platelet inhibition to ICI treatment.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Universität zu Lübeck Germany (DE) Harzklinikum Dorothea Christiane Erxleben Germany (DE) Städtisches Klinikum Dessau Germany (DE) Universitätsklinikum Leipzig Germany (DE) Carl von Ossietzky Universität Oldenburg Germany (DE) HELIOS Kliniken Germany (DE) Städtisches Klinikum Karlsruhe Germany (DE) Universitätsklinikum Halle (Saale) Germany (DE) Klinikum Darmstadt Germany (DE) Asklepios Klinikum Uckermark (AKU) Germany (DE) Technische Universität München (TUM) Germany (DE) Fachklinik Hornheide Germany (DE) Universitätsklinikum Magdeburg A.ö.R. Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Ruhr-Universität Bochum (RUB) Germany (DE) SLK-Kliniken Heilbronn GmbH Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Klinikum Nürnberg Germany (DE) Kinderkrebs-Zentrum Hamburg gGmbH Germany (DE) DRK Krankenhaus Chemnitz-Rabenstein Germany (DE) Universität Witten/Herdecke Germany (DE) Universitätsklinikum Ulm Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Essen Germany (DE) Universitätsklinikum Tübingen Germany (DE) Johannes Wesling Klinikum Minden Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Elbe Kliniken Stade-Buxtehude Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Universitätsklinikum Regensburg Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Augsburg Germany (DE) Universitätsklinikum Würzburg Germany (DE) Klinikum Dortmund Germany (DE) Klinikum Bremen-Mitte Germany (DE) Universitätsklinikum Münster Germany (DE)

How to cite

APA:

Kött, J., Zell, T., Zimmermann, N., Rünger, A., Smit, D.J., Abeck, F.,... Gebhardt, C. (2025). Improved survival of advanced melanoma patients receiving immunotherapy with concomitant antithrombotic therapy - A multicenter study on 2419 patients from the prospective skin cancer registry ADOReg. European Journal of Cancer, 214. https://doi.org/10.1016/j.ejca.2024.115159

MLA:

Kött, Julian, et al. "Improved survival of advanced melanoma patients receiving immunotherapy with concomitant antithrombotic therapy - A multicenter study on 2419 patients from the prospective skin cancer registry ADOReg." European Journal of Cancer 214 (2025).

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