The Influence of KDR Genetic Variation on the Efficacy and Safety of Patients With Advanced NSCLC Receiving First-Line Bevacizumab Plus Chemotherapy Regimen

Abstract

Objective: Angiogenesis plays an important role in the growth and metastasis of non-small cell lung cancer (NSCLC). Bevacizumab is a humanized monoclonal antibody that mainly acts on vascular endothelial growth factor A (VEGFA). Kinase insert domain receptor (KDR) is the most important target of VEGFA. The aim of present study was to investigate the influence of KDR genetic variation on the efficacy and safety of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimen. Methods: A total of 169 patients with advanced NSCLC who received bevacizumab combined with chemotherapy were recruited in this study. Clinical outcome of the regimens was evaluated in the hospital. Peripheral blood and biopsy tissue specimens of patients were collected for the genotyping of KDR genetic variation and KDR mRNA expression, respectively. The association between KDR genotype status and other variables were analyzed. Univariate analysis of genotype status and prognosis was implemented using the Kaplan-Meier survival analysis method. Multivariate Cox regression analysis was performed to adjust the confounding factors. Results: Of the polymorphisms analyzed, only V297 L was of clinical significance. The prevalence of V297 L among the study population were as follows: CC genotype 123 cases (72.8%), CT genotype 41 cases (24.3%), TT genotype 5 cases (2.9%). The minimum allele frequency is 0.15. The distribution frequencies of the 3 genotypes corresponded with Hardy-Weinberg equilibrium ( P = 0.489). Patients with TT and CT genotypes were merged in the subsequent comparison of clinical outcomes. The analysis of efficacy exhibited that the objective response rates (ORR) of patients with CC genotype and CT/TT genotypes were 52.8% and 47.8% ( P = 0.561), respectively. Prognosis indicated that the median progression free survival (PFS) of patients with CC genotype and CT/TT genotype were 8.9 and 5.5 months, respectively ( P = 0.006). The median OS of the 2 genotypes were 20.0 and 14.9 months, respectively ( P = 0.021). Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS [hazard ratio (HR) = 1.59, P = 0.011). Safety profile according to genotype status of V297 L failed to find significant difference. Interestingly, the expression of KDR mRNA of patients with CT/TT genotype was significantly higher than that of patients with CC genotype in the 58 cancer tissue specimens ( P < 0.001). Conclusion: The clinical comes of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimens might be impacted by polymorphism V297 L through mediating the mRNA expression of KDR.

Efficacy and Safety of Anlotinib Monotherapy as Third-Line Therapy for Elderly Patients with Non-Small Cell Lung Cancer: A Real-World Exploratory Study

“…To our knowledge, ECOG performance status was confirmed to be an independent prognostic factor to predict the survival among patients with NSCLC. 29 Furthermore, Cox regression analysis in our study also suggested that patients with ECOG performance status 2 score were correlated with worse PFS independently. Another two retrospective studies regarding anlotinib monotherapy for patients with previously treated NSCLC were reported recently.…”

Influence of GSTP1 Polymorphism on the Clinical Outcomes of Patients With Advanced NSCLC Receiving First-Line Bevacizumab-Based Regimen: A Real-World Retrospective Study

“…And the specific usage and dosage of chemotherapy and bevacizumab was similar with the previous study. 20…”

“…The procedure of RNA extraction and mRNA expression experiment was performed according to the previous study. 20 Forward primer of GSTP1 gene was 5’-GTAGTTTGCCCAAGGTCAAG-3,’ the reverse primer was 5’-AGCCACCTGAGGGGTAAG-3.’ In addition, GSTP1 mRNA expression status was divided into GSTP1 high expression (GSTP1H) and GSTP1 low expression (GSTP1L) according to the median GSTP1 mRNA relative expression to identify the potential association with OS.…”

“…Definition of prognostic endpoints regarding PFS and OS was used on the basis of previous work. 20 Cox regression analysis was adopted for OS for multivariable analysis. P < .05 was accepted as statistical difference.…”

“…The main inclusion criteria and exclusion criteria were adopted according to the previous retrospective study initiated by N Geng and colleagues. 20 Flow chart in Figure 1 illustrated the procedure in this study specifically. And 128 patients with advanced or recurrent NSCLC was included this study.…”