Clinical Study On The Influential Factors Of Aquired Resistance To EGFR-TKI And The Treatment Strategy After Drug Resistance In Non-small Cell Lung Cancer

Objective:In this paper,clinical studies were conducted on patients with non-small cell lung cancer(NSCLC)who were acquired resistant after first-line Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)treatment to explore the clinical influencing factors of acquired resistance with different progression patterns,At the same time,the clinical response rate and the incidence of adverse reactions of various post-drug resistance treatment strategies were analyzed,In order to find the best model of treatment after acquired resistance and provide the basis for clinical diagnosis and treatment.Methods:A total of 126 NSCLC patients with acquired resistance after first-line EGFR-TKI treatment who visited the first affiliated hospital of nanchang university from January 2012 to June 2018 were collected in this study,and divided into gradual progression group and rapid progression group according to the clinical progression model,the number of cases in the two groups was 52 cases and 74 cases respectively,the clinical data of the two groups were analyzed,Including sex?age?KPS score?tumor location?pathological type?tumor diameter?tumor stage?EGFR mutation?targeted drug type?smoking index?underlying disease?blood type?hemoglobin?albumin?tumor markers(CEA?CA125?NSE?Cyfra21-1)to explore the influencing factors acquired resistance;The post-drug resistance treatment of patients with gradual progression was analyzed retrospectively,including 19 patients in the original EGFR-TKI group(group E),14 patients in the chemotherapy group(group C)and 16 patients in the original EGFR-TKI combined with chemotherapy group(group EC).Differences of the efficacy(objective response rate(ORR)?disease control rate(DCR)?progression-free survival(PFS))and the incidence of adverse reactions(leukopenia?neutropenia?thrombocytopenia?anemia?abnormal liver function?rash?diarrhea?nausea and vomiting,etc)were compared among the three groups.Results:1.Analysis of clinical influencing factors of acquired resistance in different progression patterns: univariate analysis was carried out by comparing the clinical data of acquired resistance gradual progression group and rapid progression group.It was found that there were significant differences in tumor stage?smoking index?serum CA125 and Cyfra21-1 levels between the acquired resistance gradual progression group and th rapid progression group(P = 0.019?0.014?0.038?0.009,respectively).The results of binary Logistic analysis showed that Cyfra21-1 < 7.14 mg/ml may be an independent factor affecting the gradual progression of EGFR-TKI acquired resistance in patients with non-small cell lung cancer(P =0.026,OR = 2.831).2.The efficacy and safety of different post-drug resistance treatment strategies after gradual progress of aquired resistance:(1)Comparison of ORR and DCR among the three groups: the ORR of group E,group C and EC were 0?21.4% and 31.3%,respectively.there was significant difference in ORR between group E and group EC(P=0.013).There was no significant difference in ORR between group E and group C,group C and group EC(P>0.05).The DCR of group E,group C and EC group were 36.8%?57.1% and 81.3%,respectively.The difference of DCR between the Group E and EC two groups was statistically significant(P=0.008),but there was no significant difference in the DCR between the group E and the group C,group C and group EC(P>0.05).(2)Comparison of PFS among the three groups: the median PFS of group E,group C and group EC were 2.5 months?5.0 months and 7.0 months,there were statistically significant difference in median PFS between group E and group C,group E and group EC,group C and group EC(P values were 0.006? <0.001?0.039,respectively).(3)Comparison of incidence of adverse reactions among the three groups: There were significant differences in leukopenia,neutropenia,abnormal liver function and nausea and vomiting between group E and group C?group E and group EC(P<0.05).There were no significant differences in the three groups of adverse reactions between thrombocytopenia,anemia,rash,and diarrhea(P>0.05).Conclusions:1.Cyfra21-1 < 7.14 mg/ml may be an independent factor affecting the gradual progression of EGFR-TKI acquired resistance in patients with non-small cell lung cancer,and may be one of the biological indicators for predicting the efficacy of EGFR-TKI.2.For patients with gradual progression of acquired resistance to EGFR-TKIs,the follow-up treatment strategy of chemotherapy combined with the original targeted drugs may be more effective in prolonging PFS.3.The main adverse reactions of chemotherapy or chemotherapy combined with targeted drugs as drug resistance are leukopenia?neutropenia?abnormal liver function ? nausea and vomiting,and more related to chemotherapy itself.Chemotherapy combined with targeted drugs will not increase the risk of adverse reactions.