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417 KRAS mutant uterine carcinomas
  1. K Kilowski1,
  2. M Dietrich2,
  3. J Xiu3,
  4. J Baca3,
  5. S Ahmad1,
  6. T Herzog4,
  7. M Korn3 and
  8. R Holloway1
  1. 1AdventHealth Cancer Institute, USA
  2. 2Florida Cancer Specialists and Research Institute, USA
  3. 3Caris Life Sciences, Medical Affairs, USA
  4. 4University of Cincinnati Medical Center, USA


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 cohort

Conclusions 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.

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