| الوصف: |
Background: Somatic CDKN2A and TP53 mutations are recurrent events in melanoma, occurring in 13.3% and 15.1% of cases respectively and are associated with poorer outcomes. It is unclear what effect somatic CDKN2A and TP53 mutations have on the clinical outcomes of patients treated with checkpoint inhibitors. Methods: All patients with cutaneous melanoma or melanoma of unknown primary who received checkpoint inhibitor therapy and underwent genomic profiling with the 50-gene Mayo Clinic solid tumor targeted cancer gene panel were included. Patients were stratified according to the presence or absence of mutations in BRAF, NRAS, CDKN2A, and TP53. Patients without mutations in any of these genes were termed quadruple wild type (Quad WT ). Clinical outcomes including median time to progression (TTP), median overall survival (OS), 6-month and 12-month OS, 6-month and 12-month without progression, ORR and disease control rate (DCR) were analyzed according to the mutational status of CDKN2A, TP53 and Quad WT . Results: A total of 102 patients were included in this trial of which 14 had somatic mutations of CDKN2A (CDKN2A mut ), 21 had TP53 mutations (TP53 mut ), and 12 were Quad WT . TP53 mut , CDKN2A mut and Quad WT mutational status did not impact clinical outcomes including median TTP, median OS, 6-month and 12-month OS, 6-month and 12-month without progression, ORR and DCR. There was a trend towards improved median TTP and DCR in CDKN2A mut cohort and a trend towards worsened median TTP in the Quad WT cohort. Conclusion: Cell cycle regulators such as TP53 and CDKN2A do not appear to significantly alter clinical outcomes when immune checkpoint inhibitors are used. ; The Solid Tumor Targeted Cancer Gene Panel is a 50 gene panel that evaluated the following genes: ABL1, AKT1, ALK, APC, ATM, BRAF, CDH11, CKDN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, ... |
