Influential Factors Of The TKI Efficacy About Refractory Advanced Non-small Cell Lung Cancer With EGFR Mutation

Background:Epidemiological studies have shown that lung cancer is one of the most common malignancies in the world and in China.In the latest national death cause survey released by the Ministry of Health,lung cancer ranks first in the cause of cancer death in China,accounting for 22.7% of the nation's cancer deaths.At present,China has become the world's largest lung cancer country.The incidence of lung cancer in China is still on the rise.Regardless of the incidence or death,lung cancer is the world's first tumor.Unfortunately,2/3 of the patients diagnosed are already in advanced stages and have lost their chance of surgery.It is especially important to have standardized and comprehensive treatment for patients with advanced lung cancer.Among them,non-small cell lung cancer(NSCLC)accounts for more than 80% of lung cancer.NSCLC with the epidermal growth factor receptor(EGFR)gene mutation accounts for about 25% of lung cancer.For advanced lung cancer,the treatment is mainly chemotherapy-based comprehensive treatment,but for more than 10 years,chemotherapy-based treatments have not made breakthroughs in the treatment of lung cancer,and the the efficient of first-line standard chemotherapy regimen combined with platinum is only about 30%,the 5-year survival rate is less than 5%,and the median survival time is 8-10 months.The survival rate of lung cancer patients with first-line chemotherapy will not increase with the increase of chemotherapy dose,and the toxicity and side effects will increase accordingly.Increasing the dose of chemotherapy drugs can only lead to an increase in toxicity,but not to improve survival.With the development of molecular biology,pathology-based chemotherapy has gradually developed into molecular biology-based targeted therapy.The emergence of small molecule tyrosine kinase inhibitors(TKI)such as gefitinib and erlotinib brings longer survival benefits,lower toxicity and better quality of life for the treatment of advanced NSCLC.Most patients can be relieved for 10-13 months after EGFR-TKI treatment for the first time.Multiple studies have shown that EGFR gene mutations are effective predictors of TKI efficacy,but patients with EGFR mutations have an initial response rate of approximately 70% after TKI treatment,and approximately one-third of patients remain ineffective,and the disease progression time of each patient is inconsistent.Even some patients with EGFR wild type have a certain effect.Therefore,EGFR gene mutations are not completely predictive indicators.If we refer to the progress that occurred before the median progression-free survival(PFS)as early progression,then whether clinical indicators have an impact on the early progression of TKI-treated advanced NSCLC.Objective:This study aimed to investigate whether there are other clinical indicators besides EGFR gene mutations to judge the efficacy of TKI,and to distinguish which factors are the factors that lead to the progression of disease in TKI treatment.It is significant to guide patients' clinical treatment plan and to judge the clinical benefit of TKI treatment early.Materials and Methods1.Clinical data:A retrospective inclusion of 123 patients with advanced NSCLC with EGFR mutations,all pathological or cytologically confirmed patients,age > 18 years,with indications for TKIs treatment,clear start and end of treatment,all patients discontinued due to disease progression.The patient's pre-treatment clinical baseline data were recorded,including gender,age,smoking status,type of genetic mutation,presence or absence of brain metastases,biopsy location,targeted drug type,treatment sequence,and tumor markers.The patient developed disease within 6 months as an experimental group,and the disease progressed after 6 months as a control group.Similarly,the disease progression occurred within 12 months as an experimental group,and the disease progression occurred after 12 months as a control group.Analyze its influencing factors.2.Statistical analysis:Statistical software was used for sPss21.0 version,measurement data was expressed by(x±s),t test was used for comparison between independent groups;count data was expressed by n(%),?2 analysis was used for comparison between groups;The influencing factors were analyzed by two-class logistic regression analysis;the difference was statistically significant at the test level P<0.05.Results1.Analysis of factors affecting disease progression within 6 months: In the univariate analysis,the results showed that the targeted drugs and treatment order were the influencing factors of early disease progression within 6 months(P<0.05),so they were brought into multivariate logistic regression analysis.There were no statistically significant in gender,age,smoking,gene mutation,brain metastasis,biopsy location(P>0.05).After multivariate analysis,it was found that the targeted drug type was an independent influencing factor of disease progression within 6 months(P<0.05),and it was an independent protective factor for progression within 6 months.The OR value was 0.459.The treatment order was not independent of the drug ineffectiveness of disease progression within 6 months(P>0.05).2.Analysis of factors affecting disease progression within 12 months: After single factor analysis,the results showed that the targeted drugs,treatment sequence,and neuron-specific enolase(NSE)values were the influencing factors of disease progression within 12 months(P<0.05).),so it was brought into multivariate logistic regression analysis.Gender,age,smoking,type of gene mutation,presence or absence of brain metastasis,biopsy location,carcinoembryonic antigen(CEA)and cytokeratin fragment 19(Cyfra21-1)were not statistically significant(P>0.05).After multivariate logistic regression analysis,the results showed that the targeted drug type was an independent influencing factor of disease progression within 12 months(P<0.05),and it was an independent protective factor for disease progression within 12 months.The OR value was 0.454.The other factors of treatment order,NSE is not an independent factor of disease progression within 12 months(P>0.05).Conclusions:Through the analysis of the influencing factors affecting disease progression within 6 months and 12 months,it is found that the TKI drug type may be an independent influencing factor affecting the effect,and it has guiding significance for the selection of clinical targeted drugs,further research on the difference in TKI drug effects may be an important research direction.