Sex-specific survival in advanced metastatic melanoma - a DeCOG study on 2032 patients of the multicenter prospective skin cancer registry ADOREG
- PMID: 40749417
- DOI: 10.1016/j.ejca.2025.115668
Sex-specific survival in advanced metastatic melanoma - a DeCOG study on 2032 patients of the multicenter prospective skin cancer registry ADOREG
Abstract
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.
Keywords: Immune checkpoint inhibition therapy; Melanoma; Sex; Survival; Targeted therapy.
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carola Berking declares personal fees for consulting (advisory board, safety data monitorin board) and/or for presenting on conferences from Almirall-Hermal, BMS, Delcath, Immunocore, InflaRx, Miltenyi, MSD, Novartis, Pierre Fabre, Regeneron, Sanofi, and SkylineDx. Ralf Gutzmer declares Honoria for lectures/advice BristolMyers Squibb, MerckSharpDohme, Novartis, Merck-Serono, Almirall Hermal, Pierre-Fabre, Sun Pharma, Immunocore, Delcath, Sanofi/Regeneron, Janssen; Support of meeting participations SUN Pharma and PierreFabre; Research support (to institution) Novartis, Sanofi/Regeneron, Merck Serono, Amgen, SUN Pharma, KyowaKirin, Almirall Hermal, Recordati. Rudolf Herbst is an employee of Helios Klinikum Erfurt GmbH. Elisabeth Livingstone reports advisory role or has received honoraria/travel costs from:Bristol-Myers Squibb, Merck Sharp & Dohme, Kyowa Kirin, Novartis, Pierre Fabre, Regeneron, Sanofi, Sunpharmaand Takeda. Alexander Roesch reported grants from Novartis, Bristol Myers Squibb, and Adtec; personal fees from Merck Sharp & Dohme; and nonfinancial support from Amgen, Roche, Merck Sharp & Dohme, Novartis, Bristol Myers Squibb, and Teva. Selma Ugurel declares research support from Bristol Myers Squibb and Merck Serono; speakers and advisory board honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, and Novartis; and meeting and travel support from Almirall, Bristol-Myers Squibb, IGEA Clinical Biophysics, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Sun Pharma; outside the submitted work. Lisa Zimmer served as consultant and has received honoraria from BMS, MSD, Novartis, Pierre Fabre, Sanofi, and Sunpharma and travel support from MSD, BMS, Pierre Fabre, Sanofi, Sunpharma and Novartis, outside the submitted work. Sebastian Haferkamp received consulting fees and/or honoraria from MSD, BMS, Pierre Fabre, Immunocore and Novartis. Thilo Gambichler has received speakers and/or advisory board honoraria from BMS, Sanofi-Genzyme, MSD, Novartis Pharma, Roche, Abbvie, Almirall, Janssen, Lilly, Pfizer, Pierre-Fabre, Regeneron, and Merck-Serono outside the submitted work. Dirk Schadendorf reports partial financial support from Bristol Myers Squibb for the conduct of this study and drug supply (nivolumab and ipilimumab) support; grants (or contracts) from Amgen, Array/Pfizer, Bristol-Myers Squibb, MSD, Novartis and Roche; consulting fees from 4SC, Amgen, Array Biopharma, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Haystick, Immunocore, InFlarX, Innocent, LabCorp, Merck Serono, MSD, Nektar, NeraCare, Novartis, OncoSec, Pfizer, Philogen, Pierre Fabre, Replimune, Roche, Sandoz, Sanofi/Regeneron, Sun Pharma; honoraria from Bristol-Myers Squibb, MSD/Merck, Merck Serono, Novartis, Roche, Sanofi and Sun Pharma; support for attendings meetings or travel support from Bristol-Myers Squibb, MSD, Merck Serono, Novartis, Pierre Fabre and Sanofi; participation on drug safety monitoring or advisory boards for 4SC, Amgen, Array Biopharma, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Immunocore, InFlarX, Merck Serono, MSD, Nektar, NeraCare, Novartis, OncoSec, Pfizer, Philogen, Pierre Fabre, Replimune, Roche, Sandoz, Sanofi/Regeneron and SunPharma; leadership roles for DeCOG, German Cancer Society, Hiege-Stiftung, Deutsche Hautkrebsstiftung, NVKH e.V. and EuMelaReg. Lucie Heinzerling declares research support from Therakos; speakers and advisory board honoraria from 4SC, Amgen, BiomeDx, Bristol Myers Squibb, Curevac, Merck, Merck Sharp & Dohme, Myoncare, Novartis, Pierre Fabre, Sanofi, SUN and Roche. Patents a) intra-tumoral administration of IL-12 encoding nucleic acid molecules; Publication No.: WO/2001/052874; PCT/EP2001/000363; b) preventing secondary lymphedema with vegf-d DNA; Publication No.: WO/2003/093419; PCT/US2003/013350; c) eosinophil cationic protein (ECP) as a tumor marker for malignant tumors; Publication No.: WO/2019/219705; PCT/EP2019/062378 Ulrike Leiter declares research support from Merck Sharp & Dohme; speakers and advisory board honoraria from Merck Sharp & Dohme, Novartis, Pierre Fabre, Sun Pharma, Allmiral Hermal, Sanofi and Regeneron, and travel support from Merck Sharp & Dohme, Pierre Fabre and Sun Pharma. Carmen Loquai is part of the Advisory Boards of BMS, MSD, Merck, Roche, Immunocore, Novartis, Pierre Fabre, Sanofi, Sun Pharma, Almirall Hermal, Kyowa Kirin, Biontech and received Speakers fee from BMS, MSD, Merck, Roche, Immunocore, Novartis, Pierre Fabre, Sanofi, Sun Pharma, Almirall Hermal, Kyowa Kirin, Biontech, Lilly, travel support from BMS, MSD, Merck, Roche, Immunocore, Novartis, Pierre Fabre, Sanofi, Sun Pharma, Almirall Hermal, Kyowa Kirin, Biontech, Lilly, Pfizer, outside the submitted work. Friedegund Meier has received travel support or/and speaker’s fees or/and advisor’s honoraria by Novartis, Roche, BMS, MSD, Pierre Fabre, Sanofi and Immunocore and research funding from Novartis and Roche. Peter Mohr declares research support from Bristol Myers Squibb, Merck Sharp & Dohme and Novartis; speakers and advisory board honoraria from Bristol Myers Squibb, Beiersdorf, IO Biotech, Merck Sharp & Dohme, Pierre Fabre, Sun Pharma, Immunocore, Sanofi, Regeneron and Novartis, and travel support from Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Sun Pharma, and Pierre Fabre, outside the submitted work. Claudia Pföhler received honoraria (speaker honoraria or honoraria as a consultant) and travel support from Novartis, BMS, MSD, Merck Serono, MSD, Celgene, AbbVie, Sunpharma, Pierre Fabre, UCB, Nutricia Milupa, Janssen and LEO, outside the submitted work. Patrick Terheyden has received honoraria from Bristol Myers Squibb, Novartis, Merck Sharp & Dohme, Pierre Fabre, CureVac, Merck Serono, Sanofi, Roche, Kyowa Kirin and Biofrontera and travel support from Bristol-Myers Squibb and Pierre Fabre. Jochen Utikal is on the advisory board or has received honoraria and travel support from Amgen, Bristol Myers Squibb, GSK, Immunocore, LeoPharma, Merck Sharp and Dohme, Novartis, Pierre Fabre, Roche, Sanofi outside the submitted work. Julia Welzel is on the advisory board or has received honoraria and travel support from Abbvie, Almirall, BMS, Boehringer Ingelheim, Janssen, Infectopharm, Leo, Lilly, Mibe, MSD, Novartis, Pfizer, Sanofi. The other authors did not report conflicts of interest.
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