Impact of the Q61H mutational subtype on the response to standard first line treatment in patients with colon adenocarcinoma with KRAS mutation.

Abstract

e15603 Background: In the systemic treatment of metastatic colorectal adenocarcinoma (mCRC), the RAS/RAF/MEK/ERK MAPK pathway is a strong negative predictor of response to EGFR treatment.Studies have reported that about 40% of mCRC have KRAS mutations at codons 12 and 13. Of these mutations, KRAS G12D was mostly commonly found (36%), followed by G12V (21.8%) and G13D (18.8%). KRAS G12C has been reported to be found in about 17% of KRAS-mutated mCRC. Currently, results are mixed regarding the prognostic value of KRAS mutations. (1,2) Objective: The objective of this study is to analyze retrospectively the impact that the different KRAS mutational subtypes have had on the response to standard first line treatment for metastatic colorectal adenocarcinoma. Methods: A single-center retrospective cohort study was carried out in which 69 patients diagnosed with metastatic colorectal adenocarcinoma, with KRAS mutation, who did not undergo surgery, were analyzed between December 2016 and June 2024. Different mutation subtypes were determined by Idylla method. The response to treatment was analyzed as measured by the time from the start of the first standard line of treatment to the first progression. Results: The median age was 65 years. 41.7% were women. The distribution by location was 34.7% right, 31.9% left and 33.3% rectum. The median survival time until progression was 183.16 days. The median survival time was analyzed according to the type of mutation found using the Kruskal-Wallis statistical test for non-parametric samples, with the difference being statistically significant for the Q61H mutation subtype with respect to the rest of the subtypes. (478.5 vs 158.5 days) (p=0.036). Conclusions: In our sample, patients with the Q61H KRAS mutation subtype had a median progression-free survival that was statistically higher than the rest of the mutation subtypes. References: (1) Jones RP, Sutton PA, Evans JP, et al. Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer. Br J Cancer 2017; 116:923-929. (2) Neumann J, Zeindl-Eberhart E, Kirchner T, Jung A. Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract 2009; 205:858-862.