Characteristics of KRAS gene mutations in real clinical practice for pancreatic cancer

Background. Pancreatic cancer (PC) has long been a disease with limited treatment options, where the foundation of therapy was primarily based on cytostatics. However, with the advent of the first KRAS G12C inhibitors, new prospects have emerged for the treatment of advanced PC, highlighting the importance of studying KRAS mutations, which occur in 80–95 % of cases. In this context, it is relevant to analyze the frequency of various KRAS mutations among the Russian population of patients with PC, which could help personalize further diagnostics and therapy.

Aim. To study the features of KRAS status in patients younger and older than 65 years with pancreatic adenocarcinoma in real clinical practice.

Materials and methods. We retrospectively analyzed the data of 590 patients with pancreatic adenocarcinoma who underwent molecular genetic research and treatment at the N. N. Blokhin from 2022 to 2024. Patients with primary multiple malignancies were excluded from the study. Inclusion criteria were the presence of histological verification of the diagnosis and known KRAS, NRAS, BRCA 1/2, CHEK2, PALB2, ATM status. Patients were divided into two age groups, younger and older than 65 years. The primary endpoint was a comparative assessment of the mutation rate in both groups.

Results. 129 patients were included in the analysis. The detection rate of wild-type KRAS in the general population was 24.8 %. The most common mutations in both age groups were p.G12V and p.G12D, accounting for 79.2 % of all mutations in the KRAS gene. The p.G12C mutation was detected in two patients (2 %). Five clinically significant mutations in the BRCA 1/2 genes were identified; the patient with mBRCA1 had a wild type KRAS gene. The remaining 4 patients with a BRCA2 mutation also had a KRAS mutation.

Conclusion. Given the increasing number of drugs that affect KRAS and the ability to detect other alterations in wtKRAS, integration of KRAS testing into routine practice in the evaluation of patients with pancreatic adenocarcinoma is necessary.

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