Observation On The Efficacy Of Three Treatment Options For T790M Negative Advanced NSCLC Patients After First Generation EGFR-TKIs Resistance

Objective:To observe the efficacy of three treatment regimens and their effects on quality of life in advanced NSCLC patients who were slow progress with T790 M negative after the first generation EGFR-TKIs resistance,so as to provide basis for treatment strategies after drug resistance.Methods: Retrospectively collected clinical data of 53 patients with advanced T790 M negative who were resistant to the first generation EGFR-TKIs in our hospital from January2017 to December 2019((sex,age,smoking history,ECOG score,initial mutation type of EGFR,type of first generation EGFR-TKIs and PFS,regiment reatment after drug resistance);according to the follow-up treatment plan,it is divided into three groups: chemotherapy group,continuation of original EGFR-TKIs group and EGFR-TKIs combined with apatinib group.The efficacy evaluation was performed according to the RECIST standard.The main observation endpoint were ORR,DCR and the median PFS.Follow up the patients by phone or outpatient clinic.The serum tumor markers(CEA,CYFRA21-1)were recorded before and after treatment.The occurrence of adverse reactions during treatment and changes in quality of life score(QLQ-C30 version 3.0)were recorded,too.Patients with NSCLC whose disease progression type is outbreak progression after drug resistance were not included in this study.Results:1.In this study,a total of 53 patients were enrolled in the group.the short-term effects of the three treatment schemes were as follows: 27 patients in the chemotherapy group,ORR was 3.7%,DCR was 81.5%;15 patients in continue the original EGFR-TKIs group,ORR was 6.7%,DCR was 80%;there were 11 patients in EGFR-TKIs combined with apatinib group,ORR was 18.2%,DCR was90.9%.Comparing ORR and DCR by chi-square test,the ORR and DCR of theEGFR-TKIs combined with apatinib group were higher than those of the other two groups,but the difference was not statistically significant(P>0.05).The long-term effect of the three treatment regimens: the median PFS of the patients with EGFR-TKIs combined with apatinib was the longest in the three treatment schemes by Kaplan-Meier method,which was 6.2 months(5.622-6.778),the second was the chemotherapy group,4.9 months(4.037-5.763),and the shortest was 3.9months(3.119-4.521)in the continuation of the original EGFR-TKIs group.Further Log-rank method was used to compare the median PFS between the EGFR-TKIs combined with apatinib group and the other two groups,the difference was statistically significant(P<0.05).2.The changes of serum tumor markers in the three treatment schemes: there was no significant difference in serum tumor markers CEA and CYFRA21-1before treatment.After treatment,the level of CEA in the three groups was significantly lower than that before treatment(P<0.05);and the CEA level of the EGFR-TKIs combined with apatinib group after treatment was significantly lower than that of the other two groups,the difference was statistically significant(P<0.05).After treatment,the level of CYFRA21-1 in the three groups was lower than that before treatment,and there was significant difference in the EGFR-TKIs combined with apatinib group(P < 0.05),the difference between the other two groups was not statistically significant(P > 0.05);and the CYFRA21-1 level of EGFR-TKIs combined with apatinib group was lower than the other two groups,the difference was statistically significant(P<0.05).3.Analysis of adverse reactions of the three treatment schemes: the main adverse reactions in the chemotherapy group were nausea and vomiting(51.9%),myelosuppression(48.1%),anorexia(37.0%)and fatigue(29.6%).The adverse reactions of patients in the original EGFR-TKIs group were hand-foot syndrome(20.0%),anorexia(20.0%),fatigue(6.7%)and diarrhea(6.7%).The common adverse reactions in EGFR-TKIs combined with apatinib group were diarrhea(36.4%),hypertension(27.3%),proteinuria(18.2%)and hand-foot syndrome(18.2%),followed by bleeding(9.1%)and fatigue(9.1%).Compared with the other two groups,the EGFR-TKIs combined with apatinib group had a higher incidence of and diarrhea,hypertension,proteinuria,bleeding,while the incidences of anorexia,bone marrow suppression,and nausea and vomiting were lower.The adverse reactions with statistical differences between the groups were hypertension,proteinuria,diarrhea,hand-foot syndrome,anorexia,bone marrow suppression,nausea and vomiting(P<0.05).4.Quality of life analysis of the three treatment schemes: before receiving the three treatment options,the patients' quality of life scores were not statistically different(P>0.05).The scores of overall quality of life,physical and emotional function in the chemotherapy group were higher than those before,however,the scores of role,cognitive and social function decreased,differences are statistically significant(P< 0.05).The scores of overall quality of life,body,role and emotional function in the original EGFR-TKIs group were higher than those before,differences are statistically significant(P< 0.05),but cognitive and social function scores did not change significantly(P > 0.05).In EGFR-TKIs combined with apatinib group,the scores of overall quality of life,body,role,emotion and social function were higher than those before,differences are statistically significant(P< 0.05),cognitive function score is slightly lower than before(P> 0.05).The results of the comparison between the groups showed that after treatment,all items in the EGFR-TKIs combined with apatinib score were higher than those in the other two groups,and the differences in overall quality of life,role,emotion,cognition and social function were statistically significant Significance(P<0.05).Conclusion:1.The patients with T790M-negative advanced NSCLC after the first generation EGFR-TKIs resistance,subsequent receive EGFR-TKIs combined with apatinib have comparable short-term effects and better long-term effects than chemotherapy or continued EGFR-TKIs.2.The patients with T790M-negative advanced NSCLC after the first generation EGFR-TKIs resistance,subsequently receive EGFR-TKIs combined with apatinib,can reduce serum tumor marker levels more than chemotherapy or continued EGFR-TKIs.3.The patients with T790M-negative advanced NSCLC after the first generation of EGFR-TKIs resistance,subsequent receive EGFR-TKIs combined with apatinib showed different adverse reactions compared with chemotherapy or continued EGFR-TKIs,and overall safety was good.4.The patients with T790M-negative advanced NSCLC after the first generation of EGFR-TKIs resistance,subsequent receive EGFR-TKIs combined with apatinib can improve the overall quality of life of patients compared with chemotherapy or continued EGFR-TKIs.