RT Journal Article
SR Electronic
T1 417 KRAS mutant uterine carcinomas
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP A174
OP A174
DO 10.1136/ijgc-2020-IGCS.362
VO 30
IS Suppl 3
A1 K Kilowski
A1 M Dietrich
A1 J Xiu
A1 J Baca
A1 S Ahmad
A1 T Herzog
A1 M Korn
A1 R Holloway
YR 2020
UL http://ijgc.bmj.com/content/30/Suppl_3/A174.1.abstract
AB Background Inhibitors of KRAS mutations (KRASm) disease have shown efficacy in early clinical studies. Data informing about KRASm targeting in endometrial cancer (EC) are lacking.Methods ECs (n=8336 with various histologies) were queried for presence of actionable mutations (592 genes) and fusions (Whole Transcriptome Sequencing) using Caris Genomic Profiling database. Comparison was done using Fisher-Exact/ChiSquare (p values) and adjusted for multiple tests by Benjamini-Hochberg (q) and Pairwise nonparametric analysis using Wilcoxon Method.Results a. KRASm is a frequent genotype in Endometrial Cancer.KRASm were detected in 15.2% of EC cases. Code was most frequently mutated, with G12D (31%) and G12V (27%) being the most common subtypes (figure 1).b. Biomarkers of immunotherapy response co-occur with KRASm in EC.MSI-H/dMMR and TMB-H (>10 mt/MB) were seen 36.4% and 42.8% in KRASm and 15.9% and 27.9% in KRASwt, respectively (p>0.05).c. BRCA1/2 mutations were detected with equal frequency among KRASm and KRASwt. BRCA1/2 mutations were seen in 6% of KRASm vs 4.6% in KRASwt (p=0.033).d. KRASm are mutually exclusive of oncogenic fusions. No fusions in FGFR1/3, MET, ALK were detected concurrently with KRASm. Overall, incidence of fusion was extremely low, independent of KRAS status.Abstract 417 Figure 1 KRAS distribution in entire endometrial cohortConclusions KRASm EC represents a genomically distinct group of endometrial cancers. Targeted therapy using this biomarker should be explored in clinical trials. Overlap exists with predictors of immunotherapy response, suggesting a possible immunotherapy combination option. Clinical trials to evaluate these strategies are needed.