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Translational research

5193 - Prospective study assessing the expression of angiogenesis-related genes as markers of anti-VEGFR2 response in advanced renal cell carcinoma

Date

09 Sep 2017

Session

Translational research

Topics

Translational Research;  Renal Cell Cancer

Presenters

Jesus Garcia-Donas

Citation

Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363

Authors

J. Garcia-Donas1, N. Lainez2, M. Santos-Romero3, J. Puente4, D. Castellano5, J.F. Rodriguez-Moreno1, E. Esteban6, E. Grande Pulido7, E.M. Fernandez Parra8, L. Rodriguez Lajusticia9, M. Domenech10, E. Gonzalez Billalabeitia11, M.I. Sáez12, E. Gallardo Diaz13, S. Hernando Polo14, A. Herrador1, L. Inglada-Pérez3, M. Robledo3, C. Rodriguez-Antona3

Author affiliations

  • 1 Medical Oncology, Clara Campal Comprehensive Cancer Center, 28050 - Madrid/ES
  • 2 Medical Oncology, Complejo Hospitalario de Navarra, 31008 - Pamplona/ES
  • 3 Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center, Madrid/ES
  • 4 Medical Oncology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 5 Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 6 Medical Oncology, Hospital Universitario Central de Asturias, 33011 - Oviedo/ES
  • 7 Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 8 Medical Oncology, Hospital Nuestra Señora de Valme, 41014 - Sevilla/ES
  • 9 Medical Oncology, Hospital de Fuenlabrada, 28942 - Fuenlabrada/ES
  • 10 Medical Oncology, Hospital Althaia, Manresa/ES
  • 11 Medical Oncology, Hospital Universitario Morales Meseguer, 30008 - Murcia/ES
  • 12 Medical Oncology, H Universitario Virgen de la Victoria y Regional de Málaga, Malaga/ES
  • 13 Medical Oncology, Hospital de Sabadell Corporacis Parc Tauli, 8208 - Sabadell/ES
  • 14 Medical Oncology, HUFA Hospital Universitario Fundacion Alcorcon, 28922 - Alcorcon/ES
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Resources

Abstract 5193

Background

Since different therapeutic alternatives are reaching the clinic, we need biomarkers to guide treatment decissions in advanced Clear Cell Renal Cancer. This study explores the tumor expression of angiogenesis-related genes as potential markers of anti-VEGFR2 response.

Methods

Through an observational prospective study carried by the Spanish Oncology Genitourinary Group (SOGUG) FFPE tumor samples were collected from 159 RCC patients. A nCounter® Custom CodeSets (NanoString Technologies) was designed to measure the expression of a selected set of genes involved in angiogenesis (n = 23), immune response (n = 5) and RCC mutational landscape (n = 4), together with 4 house keeping genes. This technology was successfully applied to 135 primary tumors (81% clear cell histology), 4 metastasis, and 10 normal kidney tissues from patients treated with anti-VEGFR2 therapy. The association between the expression of the genes and PFS and OS was analyzed through cox-regression. Data provided correspond to multivariable analyses adjusted for MSKCC prognosis group, RCC histology and age.

Results

The 135 patients studied had been treated with sunitinib (91%), pazopanib (7%) or sorafenib (1%); most in first line (98%) and the median PFS was 21.0 months (95%CI=14.5-27.4). The strongest associations found corresponded to VEGFC, VEGFA, PDGFRA and FGF2. The median expression of these genes in the tumors was 28, 1075, 14 and 25 counts, respectively. High expression of VEGFC was associated with poor PFS (HR = 4.13, 95%CI=1.47-11.59, P = 0.0071) and the opposite occurred for VEGFA, which conferred longer PFS (HR = 0.05, 95%CI=0.005-0.48, P = 0.0098). PDGFRA and FGF2 were associated with poor PFS (P = 0.01 and 0.012, respectively). Regarding OS, high expression of VEGFC was associated with poor OS (HR = 6.18, 95%CI=2.03-18.77; P = 0.0013). No significant associations were found for other genes.

Conclusions

We propose that the basal tumor expression of VEGF isoforms influences the survival of the patients treated with anti-VEGFR2 drugs.

Clinical trial identification

Legal entity responsible for the study

Spanish Oncology Genitourinary Group (SOGUG)

Funding

Spanish Oncology Genitourinary Group (SOGUG)

Disclosure

All authors have declared no conflicts of interest.

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