Reconciling the Role of Vascular Endothelial Growth Factor-Targeted Therapies in Adjuvant Renal Cell Carcinoma Treatment

e15074 Background: metastatic renal cell carcinoma (mRCC) still represents a medical challenge in cancer therapy. In recent years the introduction of new targeted therapies has radically changed the approach to the disease and patients outcome. Currently the therapeutic strongholds are TKIs directed against the VEGF family (sunitinib and sorafenib). The aim of our study is to evaluate the potential predictive and prognostic role of VEGF and VEGFR polymorphisms, in determining the clinical outcome of mRCC patients receiving first-line sunitinib Methods: 41 histologic samples (biopsies and surgical specimens) of mRCC patients were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients progression free survival (PFS) and overall survival (OS) were analyzed for first line treatment. Results: VEGF A rs833061 C>T polymorphism was statistically significant in PFS (17 months for C vs 4 months for T; P = 0,0029) and OS (35,93 months for C vs 11 months for T; P = 0,0267). VEGF A rs699947 A>C was statistically significant for PFS (17 months for A vs 3,97 months for C; P = 0,0023) and OS (35,93 months for A vs 10,98 for C; P = 0,0272). VEGF A rs2010963 G>C was significant in PFS (16,98 months for G vs 4,65 for G/C vs 2,73 for C; P = 0,0188). VEGR3 rs6877011 C>G was significant in PFS (8,22 months for C vs 2,22 for C/G; P = 0,0361) and OS (35,93 months for C vs 12,08 for C/G; P = 0,0183). Conclusions: in our analysis patients with C polymorphism of rc833061, A polymorphism rs699947 and G polymorphism of rs2010963 seem to have a better PFS and OS in first line. These polymorphisms of the VEGF-A gene are probably connected with a better control of the neoangiogenesis process during TKIs therapy, maybe leading to vasculature normalization. Patients with C polymorphism of rs6877011 and G polymorphism of rs307822 seem equally to have a favourable impact in first line therapy. VEGFR-3 role is still matter of debate but seems to be involved in vessels sprouting and architecture.

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Treatment sequencing strategies in metastatic renal cell carcinoma: A critical interpretation of available data

Journal of Onco-Nephrology ◽

10.1177/2399369320943609 ◽

2020 ◽

Vol 4 (3) ◽

pp. 153-164

Author(s):

Mimma Rizzo ◽

Matteo Santoni ◽

Camillo Porta

Keyword(s):

Renal Cell Carcinoma ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Targeted Therapies ◽

Renal Cell ◽

World Population ◽

Vascular Endothelial ◽

Endothelial Growth Factor

Therapeutic sequencing strategies for metastatic renal cell carcinoma have evolved significantly over time. For about 10 years, vascular endothelial growth factor receptor-targeted therapies and mammalian target of rapamycin inhibitors have been the standard of care. About 5 years ago an immunocheckpoint inhibitor, nivolumab, has opened new therapeutic perspectives. Recent clinical studies have confirmed the biological rationale of combining two immunocheckpoint inhibitors or vascular endothelial growth factor-targeted therapies plus immunocheckpoint inhibitors, demonstrating an improvement in clinical outcomes. We are still unable to recognize immunocheckpoint inhibitors responder patients from vascular endothelial growth factor-targeted therapies responder patients and, therefore, to quantify in a certain patient the benefits/harms ratio of upfront combination over sequence therapy in a certain patient. However, the metastatic renal cell carcinoma records of high-volume cancer centers could reveal the effectiveness and tolerability of combined treatments and indicate the potentially predictive factors and the management strategies in the real-world population.

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The role of tumor vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) polymorphisms in the prediction of clinical outcome for patients with advanced renal cell carcinoma receiving first-line sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.380 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 380-380

Author(s):

Maristella Bianconi ◽

Mario Scartozzi ◽

Luca Faloppi ◽

Riccardo Giampieri ◽

Elena Maccaroni ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Renal Cell ◽

Vascular Endothelial ◽

First Line ◽

Endothelial Growth Factor

380 Background: Metastatic renal cell carcinoma (mRCC) still represents a medical challenge in cancer therapy. In recent years the introduction of new targeted therapies has radically changed the approach to the disease and patients outcome. Currently the therapeutic strongholds are TKIs directed against the VEGF family. The aim of our study is to evaluate the potential predictive and prognostic role of VEGF and VEGFR polymorphisms, in determining the clinical outcome of mRCC patients receiving first-line sunitinib. Methods: 41 histologic samples (biopsies and surgical specimens) of mRCC patients were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients progression free survival (PFS) and overall survival (OS) were analyzed for first line treatment. Results: VEGF AIV rs833061 C>T polymorphism was statistically significant in PFS (17 months for C vs 4 months for T; P = 0.0029) and OS (35.93 months for C vs 11 months for T; P = 0.0267). VEGF AV rs699947 A>C was statistically significant for PFS (17 months for A vs 3.97 months for C; P = 0.0023) and OS (35.93 months for A vs 10.98 for C; P = 0.0272). VEGF AVI rs2010963 G>C was significant in PFS (16.98 months for G vs 4.65 for G/C vs 2.73 for C; P = 0.0188). VEGR3 III rs6877011 C>G was significant in PFS (8.22 months for C vs 2.22 for C/G; P = 0.0361) and OS (35.93 months for C vs 12.08 for C/G; P = 0.0183). Conclusions: In our analysis patients with C polymorphism of rc833061 , A polymorphism rs699947 and G polymorphism of rs2010963 seem to have a better PFS and OS in first line. These polymorphisms of the VEGF-A gene are probably connected with a better control of the neoangiogenesis process during TKIs therapy, maybe leading to vasculature normalization. Patients with C polymorphism of rs6877011 seem equally to have a favourable impact in first line therapy. VEGFR-3 role is still matter of debate but seems to be involved in vessels sprouting and architecture.

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