The Impact Of Epidermal Growth Factor Receptor Mutation On The Treatment Strategy And Outcomes Of Patients With Non-small Cell Lung Cancer

BackgroundWorldwide,lung cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among men,and it is also the leading cause of cancer deaths among women in China.non-small cell lung cancer(NSCLC)constitutes approximately 80%-90% of all lung cancers.Because of the absence of symptoms in early stages,the lack of efficient lung cancer screening,and misdiagnosis,most lung cancer cases are diagnosed in advanced stages,indicating that only a minority of patients can receive surgery.Compared with best supportive care,platinum-based chemotherapy has been found to provide a survival benefit for patients with advanced lung cancer.However,most patients cannot survive more than 1 year.In the last decade,the discovery of epidermal growth factor receptor(EGFR)as a driving gene in NSCLC and the subsequent discovery of the superior efficacy of tyrosine kinase inhibitor(TKI)in patients with EGFR mutations heralded the beginning of the era of precision medicine for NSCLC.ObjectiveWe summarized the clinical data of lung cancer therapy cases at Shanghai Chest Hospital to describe the real-world impact of EGFR detection on the treatment patterns and outcomes of advanced NSCLC;to perform a analysis of lung cancer patients with uncommon EGFR mutations and to reveal their association with treatment outcomes after TKI therapy;to summarize the clinical data of non-adenocarcinoma NSCLC patients who harbored EGFR mutations to analyze their association with treatment outcomes from TKI therapy.MethodsThe clinical data of patients who were diagnosed with NSCLC at the Shanghai Chest Hospital between January 2000 and August 2014 were collected to establish a clinical database.(1)Baseline clinical characteristics included age at diagnosis,tumor histology,smoking history,sex,and EGFR mutation detection were abstracted from electronic medical records.(2)The details of therapies and survival were collected from electronic medical records or telephone follow-up.(3)The associations between patient demographics were examined using Pearson's ?2 test and the Wilcoxon-Mann-Whitney test.Survival results were analyzed using Kaplan-Meier's technique,whereas the log-rank test was used for comparisons among subgroups.Multivariable adjusted hazard ratios(HRs)for all-cause mortality by patient and treatment pattern were estimated using Cox regression.Statistical significance was defined as P < 0.05.SPSS software,version 22(SPSS Inc.,Chicago,IL,USA)was used for all statistical analyses.Results(1)The overall survival(OS)for the patients who underwent EGFR mutation detection was 18.17 months,95% confidence interval(CI),17.24–19.10.The OS for the patients who did not under EGFR mutations detection was 9.36 months,(95% CI,8.88-9.85).Patients harboring sensitive EGFR mutations(19del or 21L858R)who received TKI therapy experienced significantly improved OS(28.78 months,95% CI,27.01-30.55),compared with patients who did not receive TKI therapy(11.76 months,95% CI,9.45-14.08;adjusted HR = 0.25,95% CI,0.18-0.35;P < 0.001;).Among the patients with the EGFR wild type.TKI therapy failed to provide improved OS(14.62 months,95% CI,12.50-16.74),compared with the cohort not receiving TKI therapy(12.29 months,95% CI,11.51-13.07;adjusted HR = 0.97,95% CI,0.75-1.26;P = 0.837).(2)For patients with sensitive mutations,first-line EGFR TKI therapy(12.9 months,95% CI,10.7–15.2)provided longer progression-free survival(PFS)than did second-line EGFR TKI therapy(9.0 months,95% CI,7.7–10.2;HR: 0.78,P = 0.034).The objective response rate(ORR)of first-,and second-line TKI therapy were 67.8%,and 55.6%,respectively(P = 0.001).The OS for patients receiving first-line TKI followed by second-line chemotherapy were longer than those for patients receiving first-line chemotherapy followed by second-line TKI(HR: 0.69,P = 0.02).(3)Among the patients harboring uncommon EGFR mutations,the median PFS for patients who harbored the L861 Q,G719X,20 ins,Del-19 + L858 R,Del-19 or L858 R + T790 M were 8.90 months(95% CI,4.47-13.34),5.98 months(95% CI,1.53-10.42),2.00 months(95% CI,0.00-5.41),9.53 months(95% CI,0.00-19.41),1.94 months(95% CI,0.00-4.43),respectively.(4)The PFS for the squamous cell lung carcinoma(SCC),adenosquamous carcinoma(ASC),large cell lung cancer(LCLC)patients were 3.98 months(95% CI,3.32-4.63),8.08 months(95% CI,4.17-12.00),and 4.40 months(95% CI,1.56-7.24),respectively.Conclusion(1)EGFR gene detection is essential for the standardized treatment of NSCLC.EGFR mutation detection helped to select a subgroup of patients with common EGFR mutations who could achieved a significantly improved OS from TKI therapy.(2)Compared with second-line TKI,first-line therapy achieved a significant and longer PFS,and higher ORR in the sensitive EGFR NSCLC patients.The therapeutic strategy of using TKI followed by chemotherapy achieved longer OS than that using chemotherapy followed by TKI.(3)EGFR TKI therapy is effective in patients with L861 Q /G719X/Del-19 + L858 R,less effective in patients with 20ins/Del-19 or L858 R + T790 M.(4)EGFR TKIs could be an option for the treatment of EGFR mutated non-adenocarcinoma NSCLC,especially for patients with adenosquamous histology and non-smokers.