| Background and Objective:According to the statistics from China National Cancer Center in 2015,lung cancer is the most common cancer in China and also the leading cause of cancer deaths,with non-small cell lung cancer(NSCLC)regarded as the most frequent pathological lung cancer.When diagnosed for the first time,a large population of NSCLC are already in the advanced stage.As we know,standard chemotherapy has been the most important treatment for advanced NSCLC for a quite long time,but the emergence of epidermal growth factor tyrosine kinase inhibitors(EGFR-TKIs)changed the treatment pattern for advanced NSCLC.However,almost all patients receiving EGFR-TKIs inevitably developed drug resistance,leading to the adjustment of treatment options.Therefore,if there are prognostic biomarkers with which we can predict the treatment efficacy on patients beforehand,the treatment protocol can be adjusted beforehand as well.Previous studies have reported that the efficacy and prognosis of radiotherapy,chemotherapy,targeted therapy or surgery on NSCLC patients could be predicted with the use of systematic inflammatory markers.However,comparison between most of these markers must be done before and after medication,which is unpredictable and inconvenient.In the study,patients who were diagnosed with NSCLC in the Department of Oncology or Respiratory of Chongqing Xinqiao Hospital from January 2010 to December 2016 and who were EGFR mutated and had received first-generation EGFR-TKIs in first-line treatment were investigated.Simple biomarkers were identified by analyzing the relationship between clinical parameters and the efficacy of EGFR-TKIs.Methods:1.Patients were eligible if they had visited the Oncology or Respiratory Department of Chongqing Xinqiao Hospital from January 2010 to December 2016,received histopathological or cytological examination and EGFR genetic test,diagnosed with staged ⅣEGFR mutated NSCLC and also received first-line EGFR-TKIs monotherapy(erlotinib,gefitinib or icotinib).Then,relationship between the clinical parameters and the efficacy of EGFR-TKIs were analyzed,respectively.2.Clinical parameters that have significant influence on PFS and OS were screened,which were used for the assignment of the patients: patients with elevated clinical parameters and patients with normal clinical parameters.Differences on efficacy,PFS and OS between the two groups were analyzed.Results:1.123 patients in total were enrolled,of which 59 patients had partial response(PR,47.97%)and 64 patients had stable disease(SD,52.03%).The objective response rate(ORR)was 47.97% and objective disease control rate(DCR)was 100%.The median progression-free survival(mPFS)was 11.0 months and median overall survival(mOS)was 22.7 months.Rash,diarrhea,fatigue,nausea / vomiting and anorexia were the most common adverse events,with an incidence rate of 69.16%(74 patients),37.40%(46 patients),14.63%(18 patients),12.20%(15 patients)and 10.57%(13 patients),respectively.Patients with rash(8.94%,11 patients)or diarrhea(4.88%,6 patients)had the highest incidence of grade 3 or higher adverse events.No deaths due to serious adverse events have been reported.2.There was no significant difference in clinical parameters of efficacy evaluation between different groups.All P values were greater than 0.05.3.Univariate survival analysis indicated longer PFS in patients with lower NSE,CA125 or Cyfra21-1 before treatment(mPFS: 14.2 VS.9.1 months,P = 0.000;12.4 VS.9.5 months,P = 0.024;12.3 VS.9.5 months,P = 0.033).PS score 0-1,lower NSE,CA125,Cyfra21-1 or CA15-3 had longer OS(mOS: 24.0 VS.16.5 months,P = 0.001;27.7 VS.17.3 months,P = 0.000;25.4 VS.20.2 months,P = 0.002;25.7 VS.18.1 months,P =0.027;25.5 VS.18.7 months,P = 0.009).Multivariate analysis showed that CA125 and NSE were independent prognostic factors of PFS,while CA125,NSE,CA15-3,PS score were independent prognostic factors of OS.Compared with the results of univariate and multivariate analyses,PFS was longer when CA125 or NSE was lower before first-line EGFR-TKIs treatment and OS was longer when CA125,NSE or CA15-3 was lower or PS scored 0-1.4.The above results suggested that NSE and CA125 were independent prognostic factors of PFS and OS.123 patients were divided into two groups: patients with normal NSE and CA125(group A)and patients with elevated NSE and CA125(group B).40 patients(45.5%)were assessed PR and 48 patients(44.5%)were SD in group A while 19 patients were PR(54.3%)and 16 patients were SD(45.7%)in group B.No significant difference was found in efficacy evaluation between the two groups(P = 0.376).Median PFS was 12.3 months(95% CI:11.7-12.9 months)in group A versus 8.9 months(95%CI :7.7-10.1 months)in group B(P = 0.000).Median OS was 25.4 months(95% CI: 22.5-28.4 months)in group A and 16.0 months(95%CI:13.1-18.9 months)in group B(P = 0.000).There are significant differences in PFS and OS between group A and B.PFS and OS were both shorter in the group with elevated NSE and CA125,but longer in the group with normal NSE and CA125.Conclusions:1.Low level of NSE or CA125 before treatment indicates longer PFS in stage Ⅳ EGFR mutated NSCLC patients with first-line EGFR-TKIs therapy.2.PS scored 0-1,low level of NSE,CA125,or CA15-3 before treatment indicates longer OS in stage Ⅳ EGFR mutated NSCLC patients with first-line EGFR-TKIs therapy.3.Combination of NSE and CA125 is expected to be a simple marker for predicting the efficacy of first-line EGFR-TKIs therapy in stage Ⅳ NSCLC patients. |
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