Molecular Characteristics Of KRAS Mutations In NSCLC Patients And Their Impact On The Efficacy And Prognosis Of Immunotherapy

Objective: Non-small cell lung cancer(NSCLC)is one of the malignancies with a high incidence and mortality rate.In NSCLC,KRAS mutations are one of the common oncogenic drivers.KRAS mutation status and clinical prognosis of NSCLC immunotherapy may be correlated.The aim of this study was to explore the effect of KRAS mutation status on the efficacy and prognosis of immunotherapy in patients with stage III-IV NSCLC The present study aimed to investigate the correlation between KRAS mutation status and clinical features as well as the correlation between KRAS mutation subtypes and prognosis of immunotherapy.Methods: The clinical data of all NSCLC patients diagnosed with second-generation gene sequencing(NGS)at the Affiliated Cancer Hospital of Xinjiang Medical University between January 2017 and January 2022 were collected,and those NSCLC patients who met the entry row criteria were included in the study.The impact of KRAS mutation status on the treatment outcome of NSCLC patients was analyzed based on molecular profiles and clinical characteristics.Results:Efficacy analysis showed a higher objective remission rate(ORR)in KRAS mutant patients than in KRAS wild type(66.7% vs 38.5%,P<0.05),a statistically significant difference.After survival analysis it was found that the mean PFS of KRAS mutant and KRAS wild type patients receiving immunotherapy was 7.9 months and 3.7 months respectively,a statistically significant difference(P=0.01),and the mean OS of the two groups was 18.1 months and 12.2 months respectively,a statistically significant difference(P=0.003);immunotherapy vs chemotherapy for KRAS mutant patients PFS and OS in KRAS mutation patients treated with immunotherapy vs chemotherapy were statistically significant(P=0.01;P=0.039);PFS and OS in KRAS G12 C mutation vs KRAS non-G12 C mutation subtype patients treated with immunotherapy were not statistically different(P=0.982;P=0.866);PFS and OS in KRAS G12 C mutation patients treated with immunotherapy vs chemotherapy were not statistically(P=0.051;P=0.479);PFS after immunotherapy was statistically significant in patients with KRAS G12 D mutation vs KRAS non-G12 D mutation(P=0.005),while OS was not statistically different(P=0.23);PFS,OS and post-immunotherapy KRAS mutation in patients with both immunotherapy and a history of smoking vs KRAS wild-type patients OS and PFS and OS of KRAS mutant smokers vs non-smokers after immunotherapy were statistically different(P<0.05);PFS and OS of KRAS and TP53 co-mutant and KRAS and KMT2 C co-mutant patients who both received immunotherapy were statistically significant compared to KRAS mutant and KRAS wild-type patients alone,respectively(P<0.05).Conclusion: Among patients receiving immunotherapy,patients with KRAS mutations are more sensitive to immunotherapy and will have a better prognosis;KRAS G12 C mutant subtypes do not affect immunotherapy outcomes;KRAS and TP53 co-mutations and KRAS and KMT2 C co-mutations may have an improved response to immunotherapy.