Influence of polymorphisms of VEGFR2 on clinical outcomes and safety of advanced non-small-cell lung cancer treated by first line Bevacizumab plus chemotherapy regimens

Abstract

Objective: To investigate the influence of polymorphisms of vascular endothelial growth factor receptor-2(VEGFR2) on clinical outcomes and safety of advanced non-small-cell lung cancer (NSCLC) treated by first line Bevacizumab plus chemotherapy regimens. Methods: A total of 148 patients with advanced NSCLC who were treated by bevacizumab based first line regimens from January 2013 to January 2017 in the Department of Oncology of the First Affiliated Hospital of Zhengzhou University were included in this study. Peripheral blood and the biopsy tissue specimens of the NSCLC patients were collected for the genotyping of genetic variation and VEGFR2 mRNA expression, respectively. The association between genotype and other characteristics and VEGFR2 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. Results: Of the polymorphisms analyzed, only 889C>T was of clinical significance. Located in the coding region, the prevalence of 889C>T in VEGFR2 among the study population were as follows: CC genotype 108 cases (72.97%), CT genotype 36 cases (24.32%), TT genotype 4 cases (2.71%), minor allele frequency of 889C>T was 0.15. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.636). TT and CT genotype patients were merged in the comparison of clinical outcomes. The analysis of patients with different genotypes found that the objective response rates (ORR) of CT/TT genotypes and CC genotypes were 40.00% and 48.15% (P=0.377), respectively. And the median progression free survival (mPFS) of patients with CT/TT genotype and CC genotype were 6.1 and 8.7 months, respectively, which was statistically significant (P=0.002). In terms of overall survival (OS), the median overall survival (mOS) of the two genotypes were 18.7 and 21.4 months (P=0.012), respectively. Adjusted in multivariate analysis, 889C>T were an independent factor for progression free survival (OR=1.96, P=0.014). No association between the 889C>T and adverse reactions was found in the safety analysis. Of the 69 biopsy tissue specimens, gene expression analysis showed that the mRNA expression of VEGFR2 in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the CC genotype patients (P<0.001). Conclusion: The polymorphism 889C>T of VEGFR2 may have worse influence on clinical outcomes of advanced NSCLC treated by first line bevacizumab plus chemotherapy regimens, while no significant impact on safety.