Сибирский онкологический журнал (Mar 2022)

Mutation in the kras gene as a predictor of the effectiveness of immunotherapy for non-small cell lung cancer

  • K. K. Laktionov,
  • A. M. Kazakov,
  • K. A. Sarantseva,
  • D. S. Scherbo,
  • A. P. Koval

DOI
https://doi.org/10.21294/1814-4861-2022-21-1-115-121
Journal volume & issue
Vol. 21, no. 1
pp. 115 – 121

Abstract

Read online

The purpose of the study: to conduct a systematic literature review on the effectiveness and feasibility of using information on the presence of KRAS gene mutations (in different codons), TP 53 (KP), ST K11/LKB1 (KL), and KEAP mutations and the association of KRAS m with PD -L1 status in patients with non-small cell lung cancer (NSCLC ) as a predictor of the effectiveness of immunotherapy with immune checkpoint inhibitors.Material and Methods. The review includes data from randomized clinical trials and meta-analyses on the predictive value of KRAS mutation status for response to immunotherapy in patients with NSCLC over the past 10 years.Results. The presence of KRAS mutations in NSCLC patients could be a predictive factor for their response to immunotherapy, as several studies have demonstrated benefit from immunotherapy in these patients. The combination of KRAS mutation with TP 53 (KP) co-mutation predicts a better response to immunotherapy, while a combination with ST K11/LKB1 (KL) and KEAP 1 predicts a worse response (reduced response rate and overall and disease-free survival). In PD -L1-positive patients, the presence of KRAS mutation is associated with a better prognosis after treatment with immunotherapy. Moreover, the presence of KRAS mutation is associated with a worse response to first-line and subsequent-line chemotherapy, thus indicating a more promising use of immunotherapy in these patients.Conclusion. Identification of TP 53 (KP), ST K11/LKB1 (KL), and KEAP 1 co-mutations and the presence of KRAS mutation in addition to determination PD -L expression enable selection of patients who will obtain the greatest benefit from immunotherapy. In addition, the ability to determine KRAS mutation and co-mutation status using a liquid biopsy (with acceptable specificity and sensitivity) makes it possible to use this method for determining sensitivity to immunotherapy when it is not possible to obtain tumor sample (to determine PD 1-L1 expression).

Keywords