354P - Genetic interaction profile may predict bevacizumab (BV) efficacy in metastatic breast cancer (mBC) patients (pts): an exploratory retrospective ana...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Breast Cancer, Metastatic
Translational Research
Presenter Giacomo Allegrini
Authors G. Allegrini1, G. Bocci2, A. Fontana3, A. Camerini4, A. Ferro5, M.E. Cazzaniga6, V. Casadei7, E. Bona8, M. Scalese9, A. Falcone10
  • 1Medical Oncology Unit, Pontedera Hospital, 56025 - Pontedera/IT
  • 2Universita' Di Pisa, DIVISIONE DI FARMACOLOGIA E CHEMIOTERAPIA - DIPARTIMENTO DI MEDICINA INTERNA, PISA/IT
  • 3U.o. Oncologia Medica 2 Universitaria, Polo Oncologico, Ospedale S. Chiara, AOUP, 56100 - Pisa/IT
  • 4Oncologia Medica, Ospedale Versilia, Lido di Camaiore (LU)/IT
  • 5Struttura Complessa Di Oncologia Medica, Azienda ospedaliera San Gerardo, Monza/IT
  • 6Medical Oncology, Azienda ospedaliera San Gerardo, Monza/IT
  • 7Oncologia Medica, AOR Marche NORD, Pesaro/IT
  • 8U.o. Oncologia Medica, Oncologia Universitaria Pisa, IT- - Pisa/IT
  • 9Istituto Fisiologia Clinica, Centro Nazionale di Ricerca di Pisa, Pisa/IT
  • 10Dept. Of Oncology-presidio Ospedaliero, Polo Oncologico, Ospedale S. Chiara, AOUP, 56100 - Pisa/IT

Abstract

Background

previous retrospective studies have attempted to identify a possible role of VEGF single nucleotide polymorphisms (SNPs) to predict BV efficacy in terms of OS and PFS in MBC pts with conflicting results (Schneider 2008, Grimaldi 2011, Lambrechts 2011).

Methods

on the basis of these preliminary data, we decided to assess in a MBC population if different VEGF, VEGFR-2, IL-8, IL-6, HIF-1alfa, EPAS-1 and TSP-1 genotypes could predict first line BV + Paclitaxel (P) response in terms both of OS and PFS. Analyses were performed on germline DNA obtained from blood samples. Fourteen polymorphisms were investigated by real-time PCR technique. Both single and combinations of SNPs were investigated. The multifactor dimensionality reduction (MDR) methodology was applied to identify a genetic interaction profile for PFS (http://sourgeforge.net/projects/mdr/).

Results

102 pts have been enrolled from 8 Oncology Units. Main pts characteristics are: median age 59 years (range 32-81), ECOG-PS 0/1 in 78%/22%, hormone receptor positive 83%, previous adjuvant chemotherapy 68%, disease free interval (DFI) < 12 months 27%. After a median follow up of 17.4 months (1.9-54.7), mPFS was 11.6 months (95% CI: 10.6-12.6) and mOS was 32.4 months (95% CI: 25.9-38.9). None of SNPs were individually associated with PFS. Conversely, a genetic interaction profile consisting of VEGFR-2 rs11133360 and IL-8 rs4073 was significantly associated with PFS. mPFS was 14 months (95% CI: 11.7-16.3) and 10.9 months (95% CI: 9.3-12.4) for the favorable and unfavorable genetic profile, respectively (HR = 0.63, 95% CI: 0.4-0-99, p= 0.046). Furthermore, at the multivariate analysis hormone receptor positive (HR = 0.22, 95% CI: 0.12-0-41, p < 0.0001), DFI >12 months (HR= 0.4, 95% CI: 0.2-0.82, p= 0.011) and BV maintenance (HR = 0.63, 95% CI: 0.25.0.71, p = 0.001) were significantly associated with a better PFS.

Conclusions

genetic interaction between VEGFR-2 rs11133360 and IL-8 rs4073 polymorphisms could predict BV response in terms of PFS. With a longer follow up correlations with OS will be investigated. Prospective study is planned. Study supported by the no-profit foundation F.A.R.O.

Disclosure

All authors have declared no conflicts of interest.