Shortened progression free and overall survival to immune-checkpoint inhibitors in BRAF-, RAS- and NF1- (“Triple”) wild type melanomas
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 mul...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
September 2024
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| In: |
European journal of cancer
Year: 2024, Volume: 208, Pages: 1-10 |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2024.114208 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ejca.2024.114208 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804924008645 
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| Author Notes: | Philipp Jansen, Wolfgang Galetzka, Georg C. Lodde, Fabian Standl, Anne Zaremba, Rudolf Herbst, Patrick Terheyden, Jochen Utikal, Claudia Pföhler, Jens Ulrich, Alexander Kreuter, Peter Mohr, Ralf Gutzmer, Friedegund Meier, Edgar Dippel, Michael Weichenthal, Jan-Malte Placke, Jennifer Landsberg, Inga Möller, Antje Sucker, Annette Paschen, Eva Hadaschik, Lisa Zimmer, Elisabeth Livingstone, Dirk Schadendorf, Selma Ugurel, Andreas Stang, Klaus G. Griewank |
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| 245 | 1 | 0 | |a Shortened progression free and overall survival to immune-checkpoint inhibitors in BRAF-, RAS- and NF1- (“Triple”) wild type melanomas |c Philipp Jansen, Wolfgang Galetzka, Georg C. Lodde, Fabian Standl, Anne Zaremba, Rudolf Herbst, Patrick Terheyden, Jochen Utikal, Claudia Pföhler, Jens Ulrich, Alexander Kreuter, Peter Mohr, Ralf Gutzmer, Friedegund Meier, Edgar Dippel, Michael Weichenthal, Jan-Malte Placke, Jennifer Landsberg, Inga Möller, Antje Sucker, Annette Paschen, Eva Hadaschik, Lisa Zimmer, Elisabeth Livingstone, Dirk Schadendorf, Selma Ugurel, Andreas Stang, Klaus G. Griewank |
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| 520 | |a 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. | ||
| 650 | 4 | |a Immune therapy | |
| 650 | 4 | |a Melanoma | |
| 650 | 4 | |a Mutation profiling | |
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