200P - New imaging and molecular biomarkers to predict pathological response to bevacizumab-based treatment in neoadjuvant breast cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Breast Cancer
Translational Research
Presenter Jesus Garcia Foncillas
Authors J. Garcia Foncillas1, A. Plazaola2, B. Hernando3, R. Sanchez4, I. Alvarez5, A. Antón6, P. Martinez Del Prado7, A. Llombart Cussac8, S. Sherer9, J.M. Lopez-Vega10
  • 1Department Of Oncology, Hospital Universitario. Fundacion Jimenez Diaz. Universidad Autónoma de Madrid, 28040 - Madrid/ES
  • 2Oncology, Onkologikoa, Donosti/ES
  • 3Oncology, Hospital de Burgos, Burgos/ES
  • 4Oncology, Hospital San Pedro, Logroño/ES
  • 5Medical Oncology Dept., Hospital Donostia, 20080 - San Sebastian/ES
  • 6Oncology, H U Miguel Servet, Zaragoza/ES
  • 7Medical Oncology, Universitary Hospital of Basurto, 48013 - Bilbao/ES
  • 8Medical Oncology Service, Hospital Arnau de Vilanova, Valencia/ES
  • 9Research, Roche A.G. Basel, Basel/SZ
  • 10Servicio De Oncologia Medica, Hospital Universitario Marques de Valdecilla, Santander/ES

Abstract

Background

Early and robust prediction of pathological response in neoadjuvant breast cancer may help to identify which patients may benefit from bevacizumab-based therapy. Different imaging and molecular approaches have been 0evaluated in a multicenter clinical trial.

Methods

73 chemotherapy naïve, stage II and III breast cancer (BC) patients (pts) were enrolled in a phase II, single-arm, multicenter, open-label and prospective clinical trial. Pts received single infusion of bevacizumab (15 mg/ kg) (C1) 3 weeks prior to the beginning of neoadjuvant chemotherapy (NAC) consisting of 4 cycles of docetaxel (60 mg/mq), doxorubicin (50 mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5), followed by surgery. Tumor proliferation, hypoxia and perfusion were evaluated respectively using 18F-Fluorothymidine (FLT) and 18F-Misonidazole (FMISO) positron emission tomography (PET/CT) and dynamic contrast enhancement magnetic resonance (DCE-MR). Serial imaging studies were performed in parallel at several time points including baseline (BL) and 14-21 days after bevacizumab alone (C1). Biomarker expression was assessed by immunohistochemistry (Ki67, CD31, CD31/Ki67, VEGFR2, pVEGFR2 [Y951]) before and after bevacizumab infusion (C1). Gene expression was analyzed using Affimetrix Human Gene ST 1.0.

Results

Decrease in FMISO uptake >10% yielded a ROC curve area of 0.7 (95% CI: 0.56 - 0.85) with high specificity (94%). Decrease in the phosphorilation status of VEGFR2 (Y951) >70% yielded a receiver operating characteristic (ROC) curve area of 0.681 (95% CI: 0.536 - 0.825) with 84% sensitivity and 95% specificity. The change in phosphorilation status of VEGFR2p remains a significant predictor biomarker of response in multivariate analysis (OR = 0.9, IC%95 0.96-0.99, p = 0.04) after adjusting for clinical-pathological characteristics.

Conclusion

Our findings suggest that early changes on both biomarkers, FMISO and pVEGFR, with one cycle of bevacizumab alone predict pathological response in bevacizumab-based neoadjuvant therapy in breast cancer.

Disclosure

All authors have declared no conflicts of interest.