Abstract
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).
Highlights
Является ли само по себе наличие мутации в гене KRAS предиктором эффективности иммунотерапии? Мутация в гене KRAS встречается примерно в 15–20 % случаев Немелкоклеточный рак легкого (НМРЛ)
The presence of KRAS mutations in non-small cell lung cancer (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 TP53 (KP) co-mutation predicts a better response to immunotherapy, while a combination with STK11/LKB1 (KL) and KEAP1 predicts a worse response
Summary
Лактионов Константин Константинович, доктор медицинских наук, заведующий отделением лекарственных методов лечения No 17, ФГБУ «НМИЦ онкологии им. Блохина» Минздрава РФ; профессор кафедры онкологии и лучевой терапии лечебного факультета, ФГАОУ ВО «РНИМУ им. Казаков Алексей Михайлович, клинический ординатор, отделение лекарственных методов лечения No 17, ФГБУ «НМИЦ онкологии им. Саранцева Ксения Андреевна, кандидат медицинских наук, врач-онколог, отделение лекарственных методов лечения No 17, ФГБУ «НМИЦ онкологии им. Щербо Дмитрий Сергеевич, кандидат биологических наук, заведующий лабораторией молекулярной онкологии ФГАОУ ВО «РНИМУ им. Коваль Анастасия Павловна, кандидат биологических наук, сотрудник, лаборатория молекулярной онкологии, ФГАОУ ВО «РНИМУ им.
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