First-Line Treatment Status And Prognosis Analysis Of Advanced NSCLC Patients With Non-Classic EGFR Mutations

Background and objective:Epidermal Growth Factor Receptor(EGFR)is the most common gene mutation in non-small cell lung cancer(NSCLC),which mostly occur in exons 18-21.Deletion in exon 19 and L858 R mutations are known as classical mutations.The efficacy of EGFRTKIs in classical EGFR mutations has been largely clarified.However,for non-classic EGFR mutations,clinical decisions are still based on clinical experience,and their response to EGFR-TKIs needs to be further investigated.The purpose of this study is to investigate the first-line treatment status of NSCLC patients carrying non-classic EGFR mutations in the Cancer Center of the First Hospital of Jilin University and analyze the prognosis factors.Methods:We collected 1257 NSCLC patients carrying EGFR mutations diagnosed by histological or cytological pathology,and 88 patients were finally enrolled according to the inclusion and exclusion criteria.All data were statistically analyzed by IBM SPSS 25.0 software.Survival analysis was performed by Kaplan-Meier,and univariate analysis of prognosis was performed by Log-Rank test.Factors with P<0.05 in the results of univariate analysis were taken into the COX proportional risk model for multifactor survival analysis to find factors with independent prognostic effect on PFS and OS.P<0.05 was statistically significant.Results:1.Treatment status of NSCLC patients with EGFR non-classic mutation: 88 nonclassic EGFR mutation cases were enrolled in this study.The median age was 61 years.The median PFS and OS were respectively 10.8 months and 29.1 months.The median follow-up time was 47.3 months.For patients receiving targeted therapy and chemotherapy-based therapy,the m PFS was respectively 12.0 months and 6.8 months(P<0.001)and the mOS was respectively 34.3 months and 18.7 months(P=0.038);the differences were statistically significant.2.There was a significant difference in PFS(P=0.026)and no significant difference in OS(P=0.310)among the classical-like,PACC and Ex20 ins groups.There was no significant difference in PFS and OS among the exon 18,exon 20 and exon 21 groups.3.Subgroup analysis: According to EGFR protein structure,patients who benefited from targeted therapy were mainly PACC and classical-like type.Based on EGFR mutation exon region,patients who benefited from targeted therapy were predominantly in exon 21.4.Survival analysis: For patients with and without brain metastases,the mOS was respectively 18.7 months and 37.4 months(P=0.030).For patients aged over or equal to 65 years and those aged less than 65 years,the m PFS was respectively 6.0 months and 12.2 months(P=0.010);the mOS was respectively 17.1 months and 37.4 months(P<0.001).For patients with ECOG score 0~1 and ECOG score 2,the m PFS was respectively 11.9 months and 3.8 months(P=0.006);the mOS was respectively 33.2 months and 8.9 months(P<0.001).The effects of TNM stage,gender,and smoking history on PFS and OS were not statistically significant(P>0.05).5.Cox multivariate analysis: Aged over or equal to 65 years increased the risk of PFS events and OS events(PFS: HR=1.727,95%CI 1.075 ~ 2.774,P=0.024;OS: HR=1.791,95%CI 1.096~2.927,P=0.020).An ECOG score of 2 increased the risk of PFS and OS events(PFS: HR=2.071,95%CI 1.100 ~3.901,P=0.024;OS: HR=2.001,95%CI 1.050~3.815,P=0.035).Targeted therapy reduced the risk of PFS and OS events(PFS: HR=0.338,95%CI 0.202~0.562,P<0.001;OS: HR=0.340,95%CI 0.201~0.575,P<0.001).Conclusions:1.The classification according to the protein structure of EGFR mutation can better predict the PFS and OS of patients than according to the location of EGFR mutation.2.For NSCLC patients with non-classic EGFR mutations as a whole,targeted therapy was associated with greater PFS and OS benefit compared with chemotherapy-based therapy.3.Subgroup analysis revealed that NSCLC patients with non-classic EGFR mutations who benefited from targeted therapy were predominantly PACC/classical-like types according to EGFR protein structure and exon 21 type according to EGFR mutation exon region.4.In NSCLC patients with non-classic EGFR mutations,treatment,EGFR protein structural type,age and ECOG score were associated with PFS;treatment,presence of brain metastases at initial diagnosis,age and ECOG score were associated with OS.5.Age,ECOG score and treatment were independent prognosis factors of PFS and OS.