Huijuan Wang¹, Wanyu Tang¹, Yuanyuan Niu¹, Jie Ma², Bing Wei², Zhiyong Ma¹

¹Medical, Henan tumorhospital/ The Affiliated Cancer Hospital of Zhengzhou University, ²Molecular Pathology,Henan tumor hospital/ The Affiliated Cancer

Hospital of Zhengzhou University

Objective:The discovery of epidermal growth factorreceptor(EGFR) mutations in NSCLC opened the era of individualized therapy. Anumber of clinical studies have shown the efficacy of EGFR-tyrosine kinaseinhibitors (TKI) significantly associated with EGFR mutation status. However,the effect of TKI treatment is not always the same in the patients with EGFRmutations. Therefore propose that the abundance of EGFR gene mutation mayaffect the efficacy of EGFR TKI. This paper aims to investigate the effect ofabundance of EFGR gene mutations on the efficacy of EGFR-TKI in EGFR-mutantadvanced lung adenocarcinoma. 

Method: The Clinical data of 209 patientswith advanced lung adenocarcinoma patients were collected from January 2013 toFebruary 2015 in Henan Tumor Hospital. All the patients were detected with EGFRmutations by the department of Molecular Pathology and received EGFR-TKItreatment. EGFR mutations abundance were detected by real-time quantitativepolymerase chain reaction (PCR). The patients were divided into low abundance(<10%), in abundance (10%-30%) and high abundance (> 30%) according to theproportion of mutations. Male 84 cases, female 125 cases; median age 65years(range from 26 years to 84 years), including 29 cases of patients ≤45years old, 45 years old to 59 years old 94 patients, ≥60 years old 86 patients.152 patients were non-smoker, 57 cases with smoking history or is smoking; 4cases with the exon 18 point (Gly 719 to Ser, Ala or Cys [G719S/A/C]) mutation,102 cases with the exon 19 deletion and 103 cases with the exon 21 point (L858R)mutations. 36 cases of low abundance mutation, 102 cases of in abundancemutation, 71 cases of high abundance mutation. EGFR-TKI therapy including: Icotinib79 cases, 44 cases of erlotinib, gefitinib 86 cases. 103 cases of first-linetreatment, 106 cases of non-first-line treatment. The correlation between EGFRmutation abundance and clinical benefit from EGFR-TKI treatment was analyzed.Multivariate analyses were performed to determine correlation between clinicalbenefit and the characteristics. In all tests, P≤0.05 was considered tobe statistically significant. All statistical tests were two sided and wereperformed using SPSS software, version 17.0. 

Result: The medianprogression-free survival (PFS) of all patients received EGFR-TKI therapy was9.3 months. The PFS of advanced NSCLC patients received EGFR-TKI treatment issignificant correlated with EGFR mutations abundance (P=0.047), the PFSis longer with the higher mutation abundance, median PFS in patients with high,in, low abundance group were respectively 11.1 months (95% CI: 5.2-17.0), 9.1months (95% CI: 7.6-10.6), 7.9 months (95% CI: 4.4-11.5). But hadno-relationship with gender, age, smoking status, type of mutation, TKIcategories (P>0.05). The table below. Patients received first-linetreatment of EGFR-TKI have longer median PFS (10.7 vs. 9. 0 months, P=0.053).

Conclusion: There is a correlation between the PFS of patients with EGFRgene mutation received EGFR-TKI therapy and EGFR mutation abundance, the PFS islonger with the higher mutation abundance. For Patients with EGFR mutations,receiving TKI treatment in first-line benefit most.

Key Words: lung adenocarcinoma  Epidermal growth factor receptor