Effect of VEGF and VEGFR polymorphisms on clinical outcome and response in patients with advanced renal cell carcinoma receiving first-line treatment.

388 Background: For the last few years, sunitinib has been considered the standard treatment for first-line metastatic renal cell carcinoma, but in 2010 a new drug pazopanib had been approved for treatment in this setting. Recent data from the COMPARZ and PISCES study seem to suggest a non-inferiority of pazopanib confronted with sunitinib in PFS and OS and a patients’ preference for pazopanib if we consider quality of life parameters. The aim of our study is to investigate whether polymorphisms of VEGF and VEGFR can influence PFS and OS when patients are treated either with sunitinib or pazopanib as first-line treatment. Methods: 97 histologic samples 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: In patients treated with sunitinib VEGF-A rs833061 resulted significant in PFS (CC+CT vs TT, p < 0.0001) and OS (p < 0.0001). VEGF-A rs699947 was significant for PFS (AA+AC vs. CC) p = 0.0001) and OS (p < 0.0001). VEGF-A rs2010963 was significant in PFS (CC vs. CG vs. GG, p = 0.0001) and in OS (p = 0.0045). VEGR3 rs6877011 was significant in PFS (CC vs. CG, p = 0.0075) and OS (p = 0.0001). At multivariate analysis rs833061, rs2010963, and rs68877011 were significant in PFS. rs833061 and rs68877011 were independent factors in OS. In the pazopanib treated groups of patients VEGF-A rs833061 resulted significant in PFS (TT+CT vs. CC p = 0.027) Conclusions: In our analysis patients with CC or CT polymorphism of rc833061 had a favourable PFS and OS if treated with sunitinib instead patients treated with pazopanib seems to have benefit if CT+TT polymorphism, A polymorphism rs699947 and G polymorphism of rs2010963 seem to have a better PFS and OS in first line with sunitinib. Patients with C polymorphism of rs6877011 and G polymorphism of rs307822 seem equally to have a favourable impact in first-line therapy with sunitinib. Our data seem to suggest that biology could have a role in the choice of first-line treatment for mRCC patients. Further data will be presented at the Symposium.

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4008 POSTER Bevacizumab/interferon-alpha2a provides a progression-free survival benefit in all prespecified patient subgroups as first-line treatment of metastatic renal cell carcinoma (AVOREN)

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(07)71076-5 ◽

2007 ◽

Vol 5 (4) ◽

pp. 281-282 ◽

Cited By ~ 5

Author(s):

S. Bracarda ◽

P. Koralewski ◽

A. Pluzanska ◽

A. Ravaud ◽

C. Szczylik ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Survival Benefit ◽

Progression Free Survival ◽

Line Treatment ◽

First Line ◽

Free Survival ◽

Patient Subgroups ◽

First Line Treatment

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Axitinib in advanced renal cell carcinoma: Outcomes following pazopanib or sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.609 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 609-609 ◽

Cited By ~ 1

Author(s):

Jennifer Laskey ◽

Balaji Venugopal ◽

Nicola Thomson ◽

Roisin O'Donoghue ◽

Robert J. Jones

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Progression Free Survival ◽

Line Treatment ◽

First Line ◽

Duration Of Treatment ◽

Free Survival ◽

Line Setting ◽

First Line Treatment

609 Background: Axitinib is licensed in Europe for the treatment of adult patients with advanced renal cell carcinoma after failure of sunitinib, but not pazopanib. Efficacy is based on the AXIS trial which reported a progression free survival (PFS) of 4.8 months and an overall survival (OS) of 15.2 months in patients who had received prior sunitinib. Despite widespread use of pazopanib in the first line setting there is no randomised trial evidence to support the use of axitinib after pazopanib. The Beatson Cancer Centre (BCC) renal cancer clinic provides all systemic therapy for a population of 2.8 million. Within BCC axitinib is used post sunitinib or pazopanib. We performed an analysis of patient outcomes in patients who commenced axitinib in WOS between November 2013 and November 2014. Methods: Data were collected prospectively from the electronic clinical records. Duration of treatment was used as a surrogate for progression free survival (PFS). Data were analysed in April 2015 which served as the censor date for those still alive. Results: 46 patients were included. At the time of analysis 38 patients had stopped axitinib and 30 patients had died. 22 patients (48%) had received prior pazopanib and 21 (46%) prior sunitinib. For the patients who received axitinib in the 2nd line setting (n = 38) median duration of treatment was 4.8 months (95% CI 0.55 – 9.12). Median duration post sunitinib and pazopanib was 4.8 months (95% CI 0 – 9.7) and 5.3 months (95% CI 2.2- 8.4). Median OS was 9.2 months (95% CI 6.44 – 12.05) overall and 9.44 months (95% CI 5.36 – 13.5) and 8.36 months (95% CI 1.7 – 11.6) post sunitinib and pazopanib respectively. Conclusions: PFS appears to be comparable to reported trial data irrespective of first line treatment indicating similar efficacy and tolerability in real life. We found no evidence of a significant difference in OS regardless of first line treatment which supports the current practice of using axitinib post sunitinib or pazopanib. The inferior OS compared to AXIS trial could be multifactorial and requires further investigation.

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Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis

Therapeutic Advances in Urology ◽

10.1177/17562872211053189 ◽

2021 ◽

Vol 13 ◽

pp. 175628722110531

Author(s):

Carlo Cattrini ◽

Carlo Messina ◽

Chiara Airoldi ◽

Sebastiano Buti ◽

Giandomenico Roviello ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Meta Analysis ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

Term Survival ◽

First Line Therapy ◽

First Line Treatment

Background: In recent years, new therapeutic combinations based on immunotherapy provided significant benefits as a first-line treatment for patients with advanced renal cell carcinoma (mRCC). Objective: This work aims to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all the International Metastatic RCC Database Consortium (IMDC) subgroups. Design, setting, and participants: A systematic review and a network meta-analysis were performed. Overall survival (OS) in the intention-to-treat (ITT) population was the primary endpoint. OS according to IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed. Results and limitations: Six randomized phase III trials with 5121 patients were included. There was a high likelihood (82%) that nivolumab-cabozantinib was the preferred treatment in OS. The benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best risk/benefit ratio among all the ICI-based combinations. The limitations were the lack of individual patient data; the heterogeneity of patients’ characteristics, trial designs, and follow-up times; and a limited number of studies for indirect comparisons. Conclusions: A customized approach for the first-line treatment of patients with mRCC should consider the risk/benefit profile of each treatment option, especially considering the likeliness of long-term survival finally reached in this setting.

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