TY - JOUR
T1 - Shortened progression free and overall survival to immune-checkpoint inhibitors in BRAF-, RAS- and NF1- (“Triple”) wild type melanomas
AU - Jansen, Philipp
AU - Galetzka, Wolfgang
AU - Lodde, Georg C.
AU - Standl, Fabian
AU - Zaremba, Anne
AU - Herbst, Rudolf
AU - Terheyden, Patrick
AU - Utikal, Jochen
AU - Pföhler, Claudia
AU - Ulrich, Jens
AU - Kreuter, Alexander
AU - Mohr, Peter
AU - Gutzmer, Ralf
AU - Meier, Friedegund
AU - Dippel, Edgar
AU - Weichenthal, Michael
AU - Placke, Jan Malte
AU - Landsberg, Jennifer
AU - Möller, Inga
AU - Sucker, Antje
AU - Paschen, Annette
AU - Hadaschik, Eva
AU - Zimmer, Lisa
AU - Livingstone, Elisabeth
AU - Schadendorf, Dirk
AU - Ugurel, Selma
AU - Stang, Andreas
AU - Griewank, Klaus G.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/9
Y1 - 2024/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85198545093&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2024.114208
DO - 10.1016/j.ejca.2024.114208
M3 - Journal articles
C2 - 39018633
AN - SCOPUS:85198545093
SN - 0959-8049
VL - 208
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 114208
ER -
