Influence of genetic variation of KDR on clinical outcomes of advanced NSCLC treated by first line bevacizumab regimens

doi:10.12092/j.issn.1009-2501.2018.07.013

Abstract

Abstract:

AIM: To investigate the association between KDR gene polymorphism and the efficacy of bevacizumab in patients with advanced non-small cell lung cancer. METHODS: A total of 135 patients with advanced non-small cell lung cancer who were treated by bevacizumab based first line regimens 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 KDR gene expression, respectively. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis was adjusted by Cox regression analysis. RESULTS: Among the polymorphisms analyzed, only V297I was of clinical significance. Located in the coding region, the prevalence rates of V297I in KDR among the study population were as follows: CC genotype 99 cases (73.33%), CT genotype 33 cases (24.44%), TT genotype 3 cases (2.23%), and minor allele frequency of V297I was 0.14. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.898). TT and CT genotype patients were merged in the comparison of clinical outcomes. The analysis of patients with different genotypes found that the overall response rate (ORR) of CT/TT genotypes were 41.67% and 47.67% (P=0.549), respectively. And the median progression free survival (mPFS) of patients with CT/TT genotype and CC genotype were 6.2 and 8.6 months, respectively, which was statistically significant (P=0.003). In terms of overall survival (OS), the median overall survival (mOS) of the two genotypes were 18.9 and 21.5 (P=0.017), respectively. Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS (HR=1.95,P=0.019). Additionally, among the 68 biopsy tissue specimens, gene expression analysis was conducted. And the results showed that the expression of KDR in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the CC genotype patients (P<0.01). CONCLUSION: Among non-small cell lung cancer patients treated by bevacizumab, the polymorphism V297I of KDR may impact the clinical outcomes of first line bevacizumab treatment by influencing the mRNA expression of KDR.

Key words: non-small cell lung cancer, bevacizumab, kinase insertion region receptor, polymorphism, clinical outcomes

CLC Number:

R734.2

WANG Haixia, LIU Xingan, HOU Jiyuan, GONG Zhe, SHAN Guoyong. Influence of genetic variation of KDR on clinical outcomes of advanced NSCLC treated by first line bevacizumab regimens[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(7): 802-808.

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