Sex-specific survival in advanced metastatic melanoma: a DeCOG study on 2032 patients of the multicenter prospective skin cancer registry ADOREG

Background - Females and males differ in their innate and acquired immune responses. Thus, it is hypothesized that the efficacy of anti-tumor immunotherapies may differ by sex. This study aimed to investigate sex-specific survival differences upon different therapy types in metastatic melanoma. - Pa...

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Main Authors: Leven, Anna-Sophia (Author) , Peters, Triinu (Author) , Rajcsanyi, Luisa Sophie (Author) , Weichenthal, Michael (Author) , Mohr, Peter (Author) , Meier, Friedegund (Author) , von Wasielewski, Imke (Author) , Gutzmer, Ralf (Author) , Utikal, Jochen (Author) , Terheyden, Patrick (Author) , Herbst, Rudolf (Author) , Haferkamp, Sebastian (Author) , Pföhler, Claudia (Author) , Leiter, Ulrike (Author) , Forschner, Andrea (Author) , Kreuter, Alexander (Author) , Gebhardt, Christoffer (Author) , Lutze, Stine (Author) , Weishaupt, Carsten (Author) , Grabbe, Stephan (Author) , Debus, Dirk (Author) , Hassel, Jessica C. (Author) , Welzel, Julia (Author) , Heinzerling, Lucie (Author) , Berking, Carola (Author) , Loquai, Carmen (Author) , Gambichler, Thilo (Author) , Ziemer, Mirjana (Author) , Becker, Jürgen C. (Author) , Tasdogan, Alpaslan (Author) , Zimmer, Lisa (Author) , Livingstone, Elisabeth (Author) , Schadendorf, Dirk (Author) , Roesch, Alexander (Author) , Hinney, Anke (Author) , Ugurel, Selma (Author)
Format: Article (Journal)
Language:English
Published: 9 September 2025
In: European journal of cancer
Year: 2025, Volume: 227, Pages: 1-8
ISSN:1879-0852
DOI:10.1016/j.ejca.2025.115668
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ejca.2025.115668
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804925004502
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Author Notes:Anna-Sophia Leven, Triinu Peters, Luisa Sophie Rajcsanyi, Michael Weichenthal, Peter Mohr, Friedegund Meier, Imke von Wasielewski, Ralf Gutzmer, Jochen Utikal, Patrick Terheyden, Rudolf Herbst, Sebastian Haferkamp, Claudia Pföhler, Ulrike Leiter, Andrea Forschner, Alexander Kreuter, Christoffer Gebhardt, Stine Lutze, Carsten Weishaupt, Stephan Grabbe, Dirk Debus, Jessica Hassel, Julia Welzel, Lucie Heinzerling, Carola Berking, Carmen Loquai, Thilo Gambichler, Mirjana Ziemer, Jürgen C. Becker, Alpaslan Tasdogan, Lisa Zimmer, Elisabeth Livingstone, Dirk Schadendorf, Alexander Roesch, Anke Hinney, Selma Ugurel

MARC

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245 1 0 |a Sex-specific survival in advanced metastatic melanoma  |b a DeCOG study on 2032 patients of the multicenter prospective skin cancer registry ADOREG  |c Anna-Sophia Leven, Triinu Peters, Luisa Sophie Rajcsanyi, Michael Weichenthal, Peter Mohr, Friedegund Meier, Imke von Wasielewski, Ralf Gutzmer, Jochen Utikal, Patrick Terheyden, Rudolf Herbst, Sebastian Haferkamp, Claudia Pföhler, Ulrike Leiter, Andrea Forschner, Alexander Kreuter, Christoffer Gebhardt, Stine Lutze, Carsten Weishaupt, Stephan Grabbe, Dirk Debus, Jessica Hassel, Julia Welzel, Lucie Heinzerling, Carola Berking, Carmen Loquai, Thilo Gambichler, Mirjana Ziemer, Jürgen C. Becker, Alpaslan Tasdogan, Lisa Zimmer, Elisabeth Livingstone, Dirk Schadendorf, Alexander Roesch, Anke Hinney, Selma Ugurel 
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520 |a Background - Females and males differ in their innate and acquired immune responses. Thus, it is hypothesized that the efficacy of anti-tumor immunotherapies may differ by sex. This study aimed to investigate sex-specific survival differences upon different therapy types in metastatic melanoma. - Patients and Methods - Patients with unresectable metastatic melanoma (stage IV, AJCCv8) of the skin or unknown primary, who had received first-line PD-1-based immune checkpoint inhibition (ICI) or BRAF/MEK-directed targeted therapy (TT) were identified from the prospective multicenter DeCOG skin cancer registry ADOREG. Study endpoints were progression-free survival (PFS) and overall survival (OS). - Results - A total of 2032 patients, 1274 males (62.7%) and 758 females (37.3%), received ICI (n=1484) or TT (n=548) between May 2010 and December 2020. At median follow-up of 28.6 months, no significant sex-specific differences in survival could be detected, neither in the total cohort nor by treatment type: PFS (total, p=0.86; ICI, p=0.46; TT, p=0.21), OS (total, p=0.60; ICI, p=0.20; TT, p=0.30). Multivariable Cox regression analyses also did not show a relevant prognostic influence by sex. Subgroup analyses were performed according to ICI therapy type. In n=872 patients treated with PD-1 monotherapy, a survival advantage (PFS, p=0.041; OS, p=0.07) could be detected for males by univariable and multivariable analyses, whereas no sex-specific survival differences were found for n=456 patients who received combination immunotherapy. - Conclusion - No overall sex-specific survival differences were detected for metastatic melanoma patients in the first-line therapy setting. According to subgroup analyses males show a trend towards a survival advantage over females. 
650 4 |a Immune checkpoint inhibition therapy 
650 4 |a Melanoma 
650 4 |a Sex 
650 4 |a Survival 
650 4 |a Targeted therapy 
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