Comparison Of The Efficacy Of TKI In Patients Diagnosed With Advanced Lung Adenocarcinoma, Harboring Different EGFR, KRAS Mutation Status

Background:Advanced lung cancer had a poor prognosis, epidermal growthfactor (EGFR) mutation positive patients benefit from small moleculeinhibitor, the epidermal growth factor receptor tyrosine kinase(EGFR-TKI). EGFR mutation rate was different in different people, innon-smokers, Asian, female had a high mutation rate. Now amongpatients performance status(PS) score was2, no based-evidence medicinecompare the curative effect between EGFR mutation positive patients and"selected” patients of EGFR mutation and the relation between KRASmutation status and curative effect of TKI.Objective:To compare the1-year survival,2-year survival, PFS, overallsurvival (OS) between EGFR mutation positive patients and "selected”patients of EGFR mutation whose performance status score was2amongadvanced lung adenocarcinoma. And to explore the relation betweenclinical characteristics and survival benefits, as well as the relationbetween KRAS mutation status and curative effect of TKI.Methods: Clinical data of70patients, who diagnosed with lungadenocarcinoma, confirmed stage IIIB/IV, performance status score was2, treated with first-line TKI therapy, were obtained and analyzedretrospectively. There were35patients of EGFR positive mutation and35patients of "selected” patients of EGFR mutation. PCR and DNAsequencing were used to detect KRAS mutation status of EGFR mutationpostive patients, which both mutation positive were5cases and30cases did not have KRAS mutation. All patients were given TKItreatment. Kaplan-Meier method was used to described survival curve intwo groups and Log-rank test was used to analyze the medianprogression-free survival (PFS), overall survival (OS),1-year survivalrate,2-year survival rate in two groups. The comparion of OS and PFS inEGFR mutation positive patients with different KRAS mutation statuswere also done using the Log-rank test.Results:1. After first-line treatment with TKI among advanced lung cancerpatients whose performance status score was2, median PFS of EGFRmutation positive patients was8.2months, median PFS of " selected"patient of EGFR mutation was6.3months. There was a significantdifference of the median PFS between two groups (P=0.043);2. After first-line treatment with TKI among advanced lung cancerpatients whose performance status score was2, median OS of EGFR mutation positive patients was17.1months, median PFS of "selected" patient of EGFR mutation was9.4months. There was asignificant difference of the median OS between two groups (P=0.044);3. After first-line treatment with TKI among advanced lung cancerpatients whose performance status score was2, EGFR mutationpositive patients1year,2-year survival rate was57.1%and31.4%,"selected” patients of EGFR mutation1year,2-year survivalrate was37.1%and20%, EGFR mutation positive patients’1-yearsurvival rate,2-year survival rate were higher than the "selected”patients of EGFR mutation. There was a significant difference of the1-year survival rate,2-year survival rate between two groups (P=0.047, P=0.049);4. The subgroup analysis results showed that the median PFS offemale(P=0.003),>60years (P=0.048), non-smoker (P=0.012),clinical stage IV(P=0.049) in positive mutation of EGFR group werehigher than those of patients in "selected” patients of EGFR mutation;5. In EGFR mutation positive groups, median PFS of KRAS mutationpostive was7.0months and median PFS of KRAS mutation negativewas8.5months. There was no significant difference of the medianPFS between two groups. Median OS of KRAS mutation postive was16.8months and median OS of KRAS mutation negative was17.3 months. There was no significant difference of the median PFSbetween two groups.Conclusion:1. For advanced lung adenocarcinoma cancer patients whoseperformance status score was2when first-line treated with TKI,EGFR mutation positive patients have better curative effect thanEGFR mutation " selected" patients;2. For advanced lung cancer patients whose performance status scorewas2when first-line treated with TKI, Female,>60years,non-smoker, clinical stage IV were the impacted factors of medianPFS between EGFR mutation-positive patients and EGFR mutation"selected" patients;3. For advanced lung cancer patients whose performance status scorewas2when first-line treated with TKI, Gender, age, smokinghistory, clinical staging have no effect of OS between patients withEGFR mutation positive and EGFR mutation " selected" patients;4. In EGFR mutation positive groups, PFS and OS of KRAS mutationnegative were longer than those of KRAS mutation positive patients,but the difference was not statistically significant.