Influence of KDR Genetic Variation on the Efficacy and Safety of Patients with Chemotherapy Refractory Metastatic CRC Who Received Apatinib Treatment

Abstract

Background The aim of the present study was to investigate the influence of kinase insert domain containing receptor (KDR) genetic variation on the efficacy of treatment and safety of patients with chemotherapy-refractory metastatic colorectal cancer (CRC) receiving apatinib. Methods A total of 108 patients with chemotherapy refractory metastatic CRC who were treated with apatinib participated in this study retrospectively. Efficacy of the patients’ treatment was evaluated. Prognosis was carried out and safety profile was documented, respectively. Blood specimens and peripheral blood mononuclear cells (PBMC) of the patients were obtained for the analysis of genetic variation and KDR gene mRNA expression, respectively. The association between genotype status and clinical outcomes was presented. Results Objective response rate (ORR) and disease control rate (DCR) of the 108 patients with metastatic CRC receiving apatinib treatment were 5.6% and 69.4%, respectively. Survival analysis results exhibited that the median progression-free survival (PFS) and overall survival (OS) of the 108 patients with metastatic CRC was 3.6 months (95% confidence interval (CI): 3.03–4.17 months) and 8.9 months (95% CI: 7.57–10.23 months), respectively. Subsequently, the analysis of KDR genetic variation indicated that rs2071559 was of clinical significance. The minor allele frequency of rs2071559 was 0.22 and the genotype status corresponded with Hardy-Weinberg equilibrium ( P =0.949). Prognosis analysis in a dominant inheritance manner through the combination of patients with TC and CC genotype showed that the median PFS of patients with TT genotype and TC/CC genotype was 4.1 and 3.0 months, respectively ( P =0.012). Furthermore, the median OS of patients with the two genotypes was 10.5 and 6.1 months, respectively ( P =0.007). Additionally, multivariate Cox regression analysis of OS showed that TC/CC genotype was an independent factor for OS (Hazard ratio (HR)=0.65, P =0.021). Interestingly, mRNA expression analysis suggested that the mRNA expression of KDR in PBMC differed significantly according to rs2071559 genotype status ( P <0.001). Conclusion Apatinib demonstrated a potentially superior clinical outcome for patients with chemotherapy-refractory metastatic CRC. KDR polymorphism rs2071559 could be used as a potential biomarker for the prognosis evaluation of patients with CRC receiving apatinib therapy.

Feasibility and Safety of Anlotinib Monotherapy for Patients with Previously Treated Advanced Esophageal Squamous Cell Carcinoma: A Real-World Exploratory Study

“…To the best of our knowledge, patients with ECOG higher score had a trend to correlate with worse prognosis regardless of the therapeutic regimens. 26 Therefore, the conclusion that ECOG performance status might be used as a potential biomarker might be confirmed in prospective clinical trials subsequently. Additionally, it was noteworthy that a total of 20 patients (24.1%) had received PD-1 blockades previously, which was strikingly different from the baseline characteristics in the ALTER1102 trial (patients rarely received PD-1 blockades administration).…”

Mutational Signature and Integrative Genomic Analysis of Human Papillomavirus-Associated Penile Squamous Cell Carcinomas from Latin American Patients

“…Herein, we found 14 genes with UTR variants, of which four cancer-associated genes harbor variants in 3′ UTR ( KDR and CARD11 ) and 5′ UTR ( CSMD3 and TLX3 ). These genes have been described as oncogenes, coding for vascular endothelial growth factor receptor 2 [ 57 , 74 , 75 ], promoting cell survival by activating NF-kb [ 76 , 77 ], activating downstream MAPK/ERK signaling, inhibiting p53 and activating cMyc [ 78 , 79 ], and promoting cell growth in hematological neoplasms by activating LINC00478/miR-125b [ 80 ]. The UTR variants can alter the binding site of miRNAs, impairing their regulatory capacity; they may also generate a new binding site for other miRNAs, resulting in an imbalance of cellular homeostasis.…”

Implication of VEGFR2 Polymorphism on the Prognosis of Anlotinib Monotherapy for Patients With Treatment-Refractory Advanced NSCLC: An Exploratory Study

“…The conclusion suggested that CT/TT genotype of rs2305948 was correlated with an inferior prognosis than that of TT genotype among patients with extensive-stage SCLC. Additionally, a recent study initiated by Bai et al 12 included 108 patients with metastatic colorectal cancer and performed the exploration of the clinical impact of VEGFR2 4397T>C polymorphism. Results exhibited that patients with TT genotype of 4397T>C polymorphism predicted superior PFS and OS in patients with colorectal cancer who received apatinib administration.…”

“… 11 Additionally, previous exploratory research suggested that polymorphism of VEGFR2 might be a promising biomarker that was dramatically associated with the prognosis of patients who were treated with antiangiogenic TKI. 12 Additionally, a recent study indicated that polymorphism of −906T>C in the VEGFR2 gene might be used as a potential biomarker to predict the prognosis of patients with osteosarcoma who were treated with apatinib monotherapy. 13 Unfortunately, to our knowledge, there were still no valuable polymorphism biomarkers that were available to predict the efficacy of anlotinib monotherapy among patients with treatment-refractory advanced NSCLC currently.…”