Clinical Observation Of Clinical Benefit From Icotinib In Advanced Non-small Cell Lung Cancer

Background and objectives: Lung cancer is still the most common malignant tumor with the highest mortality in China,in which non-small cell lung cancer(NSCLC)accounts for more than 85%,while about 70% of NSCLC patients are advanced stage? B or ? patients when they diagnosed.For NSCLC patients who harbored EGFR mutation,epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)such as erlotinib,gefitinib,and icotinib have become first-line treatments according to the NCCN Guidelines.However,patients who benefit from EGFR-TKIs will obtain acquired drug resistance unavoidably within nearly one year.The clinical manifestations of different patients after drug resistance are different.Meanwhile,gene detection can not be fully popularized due to geographical,economic,personal will and other reasons at present.Therefore,it is necessary for clinicians to prejudge according to the clinical characteristics without the conditions of detection.This study aims at selecting patients with clinical benefits from Icotinib and analyzing whether the clinical features of this group were associated with EGFR mutation,mutation type or the efficacy of Icotinib.So that clinicians will able to prejudge the possible situation before making treatment plan,so as to control the whole treatment process more pertinently.Methods: We retrospectively collected 119 cases of advanced NSCLC patients from 1st May,2014 to 31 st December,2016 treated with icotinib monotherapy under first line or second line and above treatment in the Second Affiliated Hospital of Dalian Medical University.All patients were clinical diagnosed as stage IIIB or IV NSCLC confirmed by pathology or iconography and they all benefit from icotinib.Theindividual characteristics such as gender,smoking history,treatment time,tumor histology,EGFR mutation status,and clinical characteristics after drug resistance were observed.The main curative effect observation index are Time to Progression(TTP)and Post Progression Survival(PPS).Follow up the above clinical data using original medical records and telephone,the follow-up deadline is 31 st,December,2017.Using Response Evaluation Criteria In Solid Tumors(RECIST1.1)to evaluate the curative effect.The statistical were analyzed by SPSS 24.0 software,P<0.05 shows significant difference.Results:1.There was a statistical difference in smoking history among all patients with different EGFR mutation status who benefited from Icotinib(P=0.002).However,gender,age,tumor histology,stage,metastatic organ among lung,bone,brain,pleura,liver,lymph node and line of treatment has no significant difference between different EGFR mutation status(P > 0.05).2.In EGFR mutated group,people harbored L858 R mutation in exon 21 has more bone metastases than harbored deletion of exon 19(P = 0.041).3.The univariate survival analysis of TTP showed that the m TTP of all patients was 9.00 months(95%CI:7.75-10.26).The m TTP of female,nonsmokers,adenocarcinoma group was longer than that of male,smoker and non-adenocarcinoma group.However,there was no significant difference between them(P>0.05).We can not found significant difference in TTP between status of EGFR mutation,performance status,line of treatment and the previous metastases among bone,brain,pleura and liver neither.4.The univariate survival analysis of TTP showed that the m TTP of patients in stage IIIB was 11.00 months and 9.00 months in stage IV which has a statistical difference(P=0.049).The m TTP of patients who has previous intrapulmonary metastasis is 10.00 months(95%CI:7.13-12.87)and 8.00 months(95%CI:6.15-9.85)in no intrapulmonary metastasis group,which has a statistical difference(P=0.024).5.Multivariable analysis of TTP showed that intrapulmonary metastasis was anindependent factor affecting TTP(P=0.040).6.In the group of acquired resistance to Icotinib,compared to EGFR-mutated and EGFR unknown group,the proportion of patients with cough or lung disease progression was significantly higher in EGFR-wild type(P=0.004).7.In patients with acquired drug resistance,patients with new metastases after disease progression were more prone to symptom deterioration than those without new metastases,with significant differences(P < 0.001).8.In patients with both acquired drug resistance and EGFR mutation group,patients harbored L858 R mutation at exon 21 was more likely to present new metastatic after disease progression than patients with deletion of exon 19(P=0.018).9.The univariate survival analysis of PPS showed that the m PPS of all patients with acquired drug resistance to Icotinib was 7.00 months(95 CI: 5.36-8.64).Gender,age,smoking history,disease stage,line of treatment,EGFR mutation status and newly distant metastases in lung,bone,pleura and lymph node had no effect on PPS(P >0.05).10.The univariate survival analysis of PPS showed that performance status(P=0.001),tumor histology(P=0.036),symptomatic deterioration(p=0.024),new brain metastasis(P=0.037),the following treatment(P<0.001)had statistically effect on PPS.11.Multivariable analysis of PPS showed that PS?2(P=0.004),symptom deterioration(P=0.015)and BSC(P<0.001)were independent factors affecting PPS.Conclusion:1.The clinical manifestations and new metastatic organ after acquired drug resistance of Icotinib may be different due to the mutation status of EGFR and the type of EGFR mutation gene.2.NSCLC with L858 R mutation was more likely to accompany bone metastasis,and new metastatic were more likely to appear after drug resistance.3.The TTP of Icotinib treatment is correlated with disease stage and previous distant metastases such as lung metastasis.Among them,the previous intrapulmonarymetastasis can significantly shorten the TTP of patients.4.The PPS after acquired drug resistance of Icotinib is correlated with performance status symptomatic deterioration,new brain metastasis and the following treatment.Among them,PS ? 2,symptomatic deterioration and BSC after drug resistance can significantly shorten the PPS of patients.