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.
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Kött Julian, Zell Tim, Zimmermann Noah, Rünger Alessandra, Smit Daniel J, Abeck Finn, Geidel Glenn, Hansen-Abeck Inga, Heidrich Isabel, Weichenthal Michael, Ugurel Selma, Leiter Ulrike, Berking Carola, Gutzmer Ralf, Schadendorf Dirk, Zimmer Lisa, Livingstone Elisabeth, Wasielewski Imke von, Mohr Peter, Meier Friedegund, Haferkamp Sebastian, Drexler Konstantin, Herbst Rudolf, Kellner Ivonne, Utikal Jochen, Wohlfeil Sebastian A, Pföhler Claudia, Adam Leonie, Terheyden Patrick, Ulrich Jens, Meiss Frank, Möbes Monica, Welzel Julia, Schilling Bastian, Ziller Fabian, Kaatz Martin, Kreuter Alexander, Sindrilaru Anca, Dippel Edgar, Sachse Michael, Weishaupt Carsten, Hüning Svea, Heinzerling Lucie, Loquai Carmen, Schley Gaston, Gambichler Thilo, Löffler Harald, Grabbe Stephan, Schultz Erwin, Devereux Nina, Hassel Jesscia C, Simon Jan-Ch, Raap Ulrike, Assaf Chalid, Klemke Claus-Detlev, Sunderkötter Cord, Hofmann Silke C, Wenk Saskia, Tronnier Michael, Thies Silke, Heppt Markus V, Eggermont Alexander, Schulze Hans-Joachim, Zouboulis Christos C, Tüting Thomas, Bauer Alexander T, Schneider Stefan W, Gebhardt Christoffer
Аннотация
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.