Clinical outcomes and safety of apatinib monotherapy in the treatment of patients with advanced epithelial ovarian carcinoma who progressed after standard regimens and the analysis of the VEGFR2 polymorphism

Yan, Zhen; Gu, Yuanyuan; Hu, Xiaodi; Zhao, Qun; Kang, Hai-Li; Wang, Miao; Duan, Wei; Guo, Yin

doi:10.3892/ol.2020.11857

Cited by 10 publications

(12 citation statements)

References 55 publications

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“…Additionally, another study initiated by Yan and colleagues performed the association analysis between VEGFR2 gene polymorphism and efficacy of apatinib in the treatment of advanced epithelial ovarian carcinoma. 39 Results of their study indicated that the clinical outcomes of apatinib may be influenced by the polymorphism -906T>C of VEGFR2 through mediating the mRNA expression of VEGFR2 . In conclusion, these data demonstrated the potential predictive significance of polymorphism in antiangiogenic single pathway for the efficacy and prognosis of patients receiving antiangiogenic targeted drugs therapy.…”

Section: Discussionmentioning

confidence: 99%

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

Geng

Liu

et al. 2021

Technol Cancer Res Treat

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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.

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Section: Discussionmentioning

confidence: 99%

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

Geng

Liu

et al. 2021

Technol Cancer Res Treat

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“…Another previous study suggested that rs2071559 of VEGFR2 gene was of clinical significance to predict the efficacy in patients with epithelial ovarian carcinoma (EOC) treated with apatinib. 23 In conclusion, these data demonstrated the potential predictive value of KDR gene for efficacy in patients receiving apatinib treatment. However, no potential polymorphism biomarkers were available to predict the efficacy and safety of apatinib for patients with chemotherapy-refractory metastatic CRC.…”

Section: Introductionmentioning

confidence: 57%

“…The forward primer was 5ʹ-TCACTAGGGCTCTTCGTTGG-3ʹ, the reverse primer was 5ʹ-GAAGCGGATACTCAGCCAAG-3ʹ according to the previous study. 23 The size of the amplified products was 271 bp, a total of 2 μL amplified products were digested using the restriction enzyme BsmI (Thermo Fisher Scientific, USA). The genotypes of the polymorphism were distinguished through the size of PCR bands as follows: TT genotype (one 271 bp band); CC genotype (one 108 bp band and one 163 bp band); TC genotype (one 271 bp band, one 108 bp band and one 163 bp band).…”

Section: Methodsmentioning

confidence: 99%

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

Bai

2021

IJGM

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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.

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“… 36 Interestingly, the multivariate Cox regression analysis for PFS in our study also found that FIGO stage and first-line platinum response might be independent factors to predict the PFS, which was in concert with the results in a previous retrospective study regarding apatinib in EOC. 37 …”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Anlotinib Combined with PD-1 Blockades for Patients with Previously Treated Epithelial Ovarian Cancer: A Retrospective Study

Li¹,

Rao²,

Sun³

et al. 2022

IJGM

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Purpose This study was to investigate the efficacy and safety of anlotinib combined with programmed cell death protein 1 (PD-1) blockades for patients with previously treated advanced epithelial ovarian cancer (EOC). Patients and Methods Present study was designed as a retrospective study, a total of 32 patients with advanced EOC who progressed after at least two lines previously available standard therapy were included in this study. All the patients were administered with anlotinib combined with PD-1 blockades administration. Clinical activity was implemented and analyzed, which was assessed according to the change of target lesion by imaging evidence and all the subjects were followed up regularly. Safety profile were collected and documented during the treatment. Univariate analysis was carried out using log rank test and multivariate analysis were adjusted by Cox regression analysis. Results The best overall response suggested that partial response was noted in 12 patients, stable disease was observed in 14 patients, progressive disease was found in 6 patients. Therefore, the objective response rate (ORR) of the 32 patients was 37.5% (95% CI: 21.1–56.3%), disease control rate (DCR) of the patients was 81.3% (95% CI: 63.6–92.8%). The median follow-up duration of this study was 17.5 months (follow-up range: 0.9–33.5 months). And the median PFS and OS of the 32-patient cohort was 6.8 months (95% CI: 2.64–10.96) and 18.5 months (95% CI: 14.08–22.92), respectively. The most common treatment-related adverse reactions were fatigue (68.8%), nausea and vomiting (56.3%), hypertension (50.0%) and diarrhea (40.6%). Multivariate Cox regression analysis for PFS indicated that ECOG performance status and FIGO stage were independent factors to predict PFS of patients with previously treated EOC. Conclusion Anlotinib combined with PD-1 blockades demonstrated promising efficacy and tolerable safety profile for patients with previously treated advanced EOC preliminarily. The conclusion should be confirmed in more patients with advanced EOC subsequently.

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Clinical outcomes and safety of apatinib monotherapy in the treatment of patients with advanced epithelial ovarian carcinoma who progressed after standard regimens and the analysis of the VEGFR2 polymorphism

Cited by 10 publications

References 55 publications

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

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

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

Efficacy and Safety of Anlotinib Combined with PD-1 Blockades for Patients with Previously Treated Epithelial Ovarian Cancer: A Retrospective Study

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