Julian Kött, Tim Zell, Noah Zimmermann, Alessandra Rünger, Daniel J Smit, Finn Abeck, Glenn Geidel, Inga Hansen-Abeck, Isabel Heidrich, Michael Weichenthal, Selma Ugurel, Ulrike Leiter, Carola Berking, Ralf Gutzmer, Dirk Schadendorf, Lisa Zimmer, Elisabeth Livingstone, Imke von Wasielewski, Peter Mohr, Friedegund Meier, Sebastian Haferkamp, Konstantin Drexler, Rudolf Herbst, Ivonne Kellner, Jochen Utikal, Sebastian A Wohlfeil, Claudia Pföhler, Leonie Adam, Patrick Terheyden, Jens Ulrich, Frank Meiss, Monica Möbes, Julia Welzel, Bastian Schilling, Fabian Ziller, Martin Kaatz, Alexander Kreuter, Anca Sindrilaru, Edgar Dippel, Michael Sachse, Carsten Weishaupt, Svea Hüning, Lucie Heinzerling, Carmen Loquai, Gaston Schley, Thilo Gambichler, Harald Löffler, Stephan Grabbe, Erwin Schultz, Nina Devereux, Jesscia C Hassel, Jan-Ch Simon, Ulrike Raap, Chalid Assaf, Claus-Detlev Klemke, Cord Sunderkötter, Silke C Hofmann, Saskia Wenk, Michael Tronnier, Silke Thies, Markus V Heppt, Alexander Eggermont, Hans-Joachim Schulze, Christos C Zouboulis, Thomas Tüting, Alexander T Bauer, Stefan W Schneider, Christoffer Gebhardt
{"title":"接受免疫治疗和联合抗血栓治疗的晚期黑色素瘤患者生存率提高——一项来自ADOReg前瞻性皮肤癌登记的2419例患者的多中心研究。","authors":"Julian Kött, Tim Zell, Noah Zimmermann, Alessandra Rünger, Daniel J Smit, Finn Abeck, Glenn Geidel, Inga Hansen-Abeck, Isabel Heidrich, Michael Weichenthal, Selma Ugurel, Ulrike Leiter, Carola Berking, Ralf Gutzmer, Dirk Schadendorf, Lisa Zimmer, Elisabeth Livingstone, Imke von Wasielewski, Peter Mohr, Friedegund Meier, Sebastian Haferkamp, Konstantin Drexler, Rudolf Herbst, Ivonne Kellner, Jochen Utikal, Sebastian A Wohlfeil, Claudia Pföhler, Leonie Adam, Patrick Terheyden, Jens Ulrich, Frank Meiss, Monica Möbes, Julia Welzel, Bastian Schilling, Fabian Ziller, Martin Kaatz, Alexander Kreuter, Anca Sindrilaru, Edgar Dippel, Michael Sachse, Carsten Weishaupt, Svea Hüning, Lucie Heinzerling, Carmen Loquai, Gaston Schley, Thilo Gambichler, Harald Löffler, Stephan Grabbe, Erwin Schultz, Nina Devereux, Jesscia C Hassel, Jan-Ch Simon, Ulrike Raap, Chalid Assaf, Claus-Detlev Klemke, Cord Sunderkötter, Silke C Hofmann, Saskia Wenk, Michael Tronnier, Silke Thies, Markus V Heppt, Alexander Eggermont, Hans-Joachim Schulze, Christos C Zouboulis, Thomas Tüting, Alexander T Bauer, Stefan W Schneider, Christoffer Gebhardt","doi":"10.1016/j.ejca.2024.115159","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"115159"},"PeriodicalIF":7.6000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Julian Kött, Tim Zell, Noah Zimmermann, Alessandra Rünger, Daniel J Smit, Finn Abeck, Glenn Geidel, Inga Hansen-Abeck, Isabel Heidrich, Michael Weichenthal, Selma Ugurel, Ulrike Leiter, Carola Berking, Ralf Gutzmer, Dirk Schadendorf, Lisa Zimmer, Elisabeth Livingstone, Imke von Wasielewski, Peter Mohr, Friedegund Meier, Sebastian Haferkamp, Konstantin Drexler, Rudolf Herbst, Ivonne Kellner, Jochen Utikal, Sebastian A Wohlfeil, Claudia Pföhler, Leonie Adam, Patrick Terheyden, Jens Ulrich, Frank Meiss, Monica Möbes, Julia Welzel, Bastian Schilling, Fabian Ziller, Martin Kaatz, Alexander Kreuter, Anca Sindrilaru, Edgar Dippel, Michael Sachse, Carsten Weishaupt, Svea Hüning, Lucie Heinzerling, Carmen Loquai, Gaston Schley, Thilo Gambichler, Harald Löffler, Stephan Grabbe, Erwin Schultz, Nina Devereux, Jesscia C Hassel, Jan-Ch Simon, Ulrike Raap, Chalid Assaf, Claus-Detlev Klemke, Cord Sunderkötter, Silke C Hofmann, Saskia Wenk, Michael Tronnier, Silke Thies, Markus V Heppt, Alexander Eggermont, Hans-Joachim Schulze, Christos C Zouboulis, Thomas Tüting, Alexander T Bauer, Stefan W Schneider, Christoffer Gebhardt\",\"doi\":\"10.1016/j.ejca.2024.115159\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":11980,\"journal\":{\"name\":\"European Journal of Cancer\",\"volume\":\"214 \",\"pages\":\"115159\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ejca.2024.115159\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ejca.2024.115159","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：癌症免疫治疗已经彻底改变了黑色素瘤的治疗，但大量的无反应仍然强调需要改进治疗。增强抗肿瘤治疗的一个潜在途径是通过调节凝血和血小板活性。两者都在肿瘤微环境、肿瘤生长和转移中发挥重要作用。临床前研究表明其有益效果，但临床数据一直不一致。方法：我们研究了一组来自德国前瞻性多中心皮肤癌登记处ADOReg的晚期不可切除黑色素瘤患者（n = 2419），这些患者接受免疫检查点抑制剂（ICI）治疗。根据是否在ICI开始时接受血小板聚集抑制（PAI） （n = 137）（乙酰水杨酸（ASA）或氯吡格雷），抗凝（AC） （n = 185）（直接口服抗凝（DOAC）， phenprocoumon，肝素）或在ICI治疗期间的任何时间点未使用抗血栓药物（n = 2097）对患者进行分类。研究终点为最佳总缓解（BOR）、无进展生存期（PFS）和总生存期（OS）。结果：与未接受抗栓药物治疗的患者相比，接受ASA治疗的患者（15.1 vs 6.4个月，HR 0.67, 95% CI: 0.5 ~ 0.88, p = 0.0047）和接受AC治疗的患者（15.1 vs 6.4个月，HR 0.7, 95% CI: 0.53 ~ 0.91, p = 0.01）的PFS显著改善。多因素OS分析显示，接受DOAC （HR 0.68, 95% CI: 0.49 ~ 0.92, p = 0.0170）或phenprocoumon （HR: 0.44, 95% CI: 0.19 ~ 0.85, p = 0.0301）的患者风险显著降低。结论：我们的研究表明抗凝血和抗血小板联合用药对接受ICI的黑色素瘤患者的预后有积极的影响。需要进一步的研究来证实在ICI治疗中加入抗凝或血小板抑制的癌症相关益处。
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.
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.
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