[Influence of apatinib and VEGFR2-906T>C polymorphism on clinical outcomes of advanced non-small cell lung cancer patients].

To investigate the clinical outcomes of advanced non-small cell lung cancer (NSCLC) treated by apatinib regimens and the influence of VEGFR2-906T>C polymorphism. A total of 109 patients with advanced NSCLC who were treated by apatinib after three and more lines from March 2015 to December 2017 in the Department of Oncology of the First Affiliated Hospital of Zhengzhou University were included in this study. Overall response rates were evaluated after 2 cycles, then progression free survival (PFS) and overall survival (OS) were investigated, and safety data were recorded. Additionally, peripheral blood and the biopsy tissue specimens of some NSCLC patients were collected for the genotyping of genetic variation and VEGFR2 gene mRNA expression, respectively. The association between genotype and other characteristics and VEGFR2 gene mRNA expression were analyzed. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis were adjusted by Cox regression analysis. The treatment effect could be evaluated in all the 109 patients, among them, complete remission (CR) 0 case, partial remission (PR) 19 case, stable disease (SD) 58 case, progression disease (PD) 32 case. Overall response rate (ORR) was 17.43%, disease control rate (DCR) was 70.64%, median PFS was 4.35 months, median OS was 8.35 months. Of the polymorphisms analyzed, only -906T>C was of clinical significance. The prevalence of -906T>C in VEGFR2 among the study population were as follows: TT genotype 64 cases (58.72%), TC genotype 37 cases (33.94%), CC genotype 8 cases (7.34%), minor allele frequency of -906T>C was 0.24. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (0.418). CC and TC genotype patients were merged in the comparison of clinical outcomes. The analysis of patients with different genotypes found that the ORR of CC/TC genotypes and TT genotypes were 13.33% and 20.31% (0.377), respectively. And the median PFS of patients with CC/TC genotype and TT genotype were 3.25 and 5.35 months, respectively, which was statistically significant (0.007). In terms of OS, the median OS of the two genotypes were 7.35 and 9.15 (0.014), respectively. Adjusted in multivariate Cox regression analysis of PFS, TC/CC genotypes were an independent factor for PFS (1.83, 0.015). The correlation between -906T>C and adverse reactions was not found in the safety analysis. Additionally, of the 69 biopsy tissue specimens, gene expression analysis was conducted. And the results show that the mRNA expression of VEGFR2 in cancer tissues of the patients with CC/TC genotypes were significantly higher than those of the TT genotype patients (0.001). Apatinib is safe and effective for patients with advanced non-small cell in multiline therapy. VEGFR2 -906T>C CC/TC genotype has a worse effect on apatinib multiline treatment in patients with advanced NSCLC.