Shortened progression free and overall survival to immune-checkpoint inhibitors in BRAF-, RAS- and NF1- ("Triple") wild type melanomas.

Autor: Jansen P; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany; Department of Dermatology, University Hospital Bonn, Bonn. Electronic address: philipp.jansen@ukbonn.de., Galetzka W; Institute for medical informatics, biometry and epidemiology, University Hospital Essen, Essen, Germany., Lodde GC; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Standl F; Institute for medical informatics, biometry and epidemiology, University Hospital Essen, Essen, Germany., Zaremba A; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Herbst R; Hauttumorzentrum, Helios Klinikum Erfurt, Erfurt, Germany., Terheyden P; Department of Dermatology, UKSH Campus Lübeck, Lübeck, Germany., Utikal J; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Heidelberg, Germany., Pföhler C; Department of Dermatology, Saarland University Medical School, Homburg, Saar, Germany., Ulrich J; Department of Dermatology and Venereology, Harzklinikum Dorothea Christiane Erxleben, Quedlinburg, Germany., Kreuter A; Department of Dermatology, Venereology and Allergology, HELIOS St. Elisabeth Klinik Oberhausen, University Witten/Herdecke, Oberhausen, Germany., Mohr P; Dermatological Center Buxtehude, Elbe Kliniken Buxtehude, Buxtehude, Germany., Gutzmer R; Skin Cancer Unit, Hannover Medical School, Hannover, Germany & Department of Dermatology, Johannes Wesling Medical Center, Ruhr University Bochum, Minden, Germany., Meier F; Department of Dermatology, Dermatooncology, University Hospital Carl Gustav Carus, TU Dresden, Dresden Germany., Dippel E; Department of Dermatology Ludwigshafen, Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Ludwigshafen, Germany., Weichenthal M; University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany., Placke JM; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Landsberg J; Department of Dermatology, University Hospital Bonn, Bonn., Möller I; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Sucker A; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Paschen A; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Hadaschik E; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Zimmer L; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Livingstone E; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Schadendorf D; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Ugurel S; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany., Stang A; Institute for medical informatics, biometry and epidemiology, University Hospital Essen, Essen, Germany., Griewank KG; Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium (DKTK), partner site Essen, Düsseldorf, Germany.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2024 Sep; Vol. 208, pp. 114208. Date of Electronic Publication: 2024 Jul 06.
DOI: 10.1016/j.ejca.2024.114208
Abstrakt: Background: Melanomas lacking mutations in BRAF, NRAS and NF1 are frequently referred to as "triple wild-type" (tWT) melanomas. They constitute 5-10 % of all melanomas and remain poorly characterized regarding clinical characteristics and response to therapy. This study investigates the largest multicenter collection of tWT-melanomas to date.
Methods: Targeted next-generation sequencing of the TERT promoter and 29 melanoma-associated genes were performed on 3109 melanoma tissue samples of the prospective multicenter study ADOREG/TRIM of the DeCOG revealing 292 patients suffering from tWT-melanomas. Clinical characteristics and mutational patterns were analyzed. As subgroup analysis, we analyzed 141 tWT-melanoma patients receiving either anti-CTLA4 plus anti-PD1 or anti PD1 monotherapy as first line therapy in AJCC stage IV.
Results: 184 patients with cutaneous melanomas, 56 patients with mucosal melanomas, 34 patients with acral melanomas and 18 patients with melanomas of unknown origin (MUP) were included. A TERT promoter mutation could be identified in 33.2 % of all melanomas and 70.5 % of all tWT-melanomas harbored less than three mutations per sample. For the 141 patients with stage IV disease, mPFS independent of melanoma type was 6.2 months (95 % CI: 4-9) and mOS was 24.8 months (95 % CI: 14.2-53.4) after first line anti-CTLA4 plus anti-PD1 therapy. After first-line anti-PD1 monotherapy, mPFS was 4 months (95 %CI: 2.9-8.5) and mOS was 29.18 months (95 % CI: 17.5-46.2).
Conclusions: While known prognostic factors such as TERT promoter mutations and TMB were equally distributed among patients who received either anti-CTLA4 plus anti-PD1 combination therapy or anti-PD1 monotherapy as first line therapy, we did not find a prolonged mPFS or mOS in either of those. For both therapy concepts, mPFS and mOS were considerably shorter than reported for melanomas with known oncogene mutations.
Competing Interests: Declaration of Competing Interest All other authors declare no conflicts of interest for the submitted work.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: