KRAS突变亚型及共突变状态对晚期非鳞非小细胞肺癌疗效与生存的影响分析OA

Objective To investigate the impact of different KRAS mutation subtypes and co-mutation status on the efficacy and prognosis in patients with advanced non-squamous NSCLC,aiming to optimize individualized clinical treatment strategies.Method A retrospective analysis was conducted on 114 patients with KRAS-mutated advanced non-squamous NSCLC admitted to three medical centers of Chinese PLA General Hospital from 2015 to 2025.Clinical data,genetic testing results and follow-up data were collected.Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1.Kaplan-Meier method was used to estimate the median progression-free survival(mPFS)and median overall survival(mOS).Result A total of 114 patients with confirmed KRAS mutation subtypes were enrolled,among whom males accounted for 78.95%and patients at stage Ⅳ accounted for 92.98%.The main subtypes were G12C(34.21%)and G12D(21.93%).The smoking rate was the highest in the G12C group(84.62%)and the lowest in the G12D group(56.00%).Among first-line treatments,the immunotherapy±chemotherapy group had a median PFS of 10.50 months and a median OS of 17.80 months;the chemotherapy plus bevacizumab group had 6.63 months and 19.10 months,respectively;and the immunotherapy plus chemotherapy plus bevacizumab group had 8.77 months and 18.73 months,respectively,with no statistically significant differences among the groups.In terms of efficacy,the mPFS and mOS in the G12C group were 11.47 months and 21.48 months,respectively;those in the G12D group were 7.85 months and 16.33 months,respectively.There was no statistically significant difference in PFS between the different subtypes.Although the G12C group showed a numerical trend towards longer median OS compared to non-G12C patients,the difference was not statistically significant.Co-mutation analysis:mPFS in patients with TP53 co-mutation was 8.67 months,and mOS was 20.00 months.For patients with STK11 co-mutation,mPFS was 8.37 months and mOS was 13.07 months.KRAS co-mutated with TP53 showed a trend of survival benefit,but the difference was not statistically significant;whereas KRAS co-mutated with STK11 indicated poor prognosis.Conclusion For advanced non-squamous NSCLC with KRAS mutations,immunotherapy-based combination therapy is the preferred first-line treatment,and the addition of antiangiogenic agents does not further improve efficacy.In the context of conventional chemotherapy and immunotherapy,KRAS mutation subtypes other than G12C(G12D,G12V,G12A)have no significant favorable impact on prognosis and are independent unfavorable prognostic factors.The G12C subtype shows a trend toward survival benefit.KRAS co-mutated with TP53 shows a trend toward survival benefit,whereas KRAS co-mutated with STK11 indicates poor prognosis.Clinical decision-making should focus on biomarkers such as co-mutation status,PD-L1 expression level,and smoking history,rather than over-relying on KRAS mutation subtypes for stratification.