1648P - Neoadjuvant addition of bevacizumab to chemoradiation in rectal cancer: impact on angiogenic biomarkers

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Anti-Cancer Agents & Biologic Therapy
Rectal Cancer
Surgery and/or Radiotherapy of Cancer
Presenter Berta Laquente
Authors B. Laquente1, J. Capdevila2, M. Martínez-Villacampa3, C. López4, M.J. Safont5, A. Gómez6, J.L. Manzano7, C. Grávalos8, R. Salazar3, E. Aranda Aguilar9
  • 1Medical Oncology, ICO. Hospital Duran i Reynals, 08907 - Barcelona/ES
  • 2Medical Oncology, Hospital Vall d'Hebrón, Barcelona/ES
  • 3Medical Oncology, ICO Hospital Duran i Reynals, Barcelona/ES
  • 4Medical Oncology, Hospital Marqués de Valdecilla, Santander/ES
  • 5Medical Oncology, Hospital General de Valencia, Valencia/ES
  • 6Medical Oncology, Hospital Reina Sofía, Córdoba/ES
  • 7Medical Oncology, ICO Hospital Germans Trias i Pujol, Barcelona/ES
  • 8Medical Oncology, Hospital Doce de Octubre, Madrid/ES
  • 9Medical Oncology Dpto, Hospital Reina Sofía, Córdoba/ES

Abstract

Purpose

We report the clinical results of adding bevacizumab (BEV) to preoperative chemoradiation (CRT), in patients (pts) with locally advanced rectal cancer (LARC). This pre-planned sub-study was aimed to evaluate the evolution of several biomarkers and their correlation with downstaging.

Methods

Patients with LARC were randomized to radiotherapy 45Gy/25f/5 weeks + capecitabine (CAP: 825mg/m/bid) + BEV every 2 weeks (5 mg/kg for 3 doses) (arm A) or the same schedule without BEV (arm B): surgery was scheduled 6-8 weeks after completing CRT. Plasma levels of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR-2) and angiopoietin-2 (Ang-2) were measured at baseline (d1), day 15 (d15) and day 57 (d57). Tissue samples (baseline and at surgery) were assessed for microvessel density (MVD). Comparisons between concentrations at different time points were assessed by using appropriate statistical paired tests. Logistic regression model was adopted to estimate and test the biomarkers for their association with downstaging.

Results

Samples for biomarker analyses were obtained for 50 out of 90 randomized pts (arm A/B: 22/28): paired plasma samples were available for 18/23 pts at d1 and d15, and for 14/17 pts at d57; paired tumor samples were obtained from 12/18 pts. Eleven pts in each arm were downstaged (lower pT compared with the pretreatment cT). No differences were observed in baseline levels of any biomarker between both arms. Ang-2 levels were significantly higher in arm B than in arm A at d15 and d57 (p = 0.0056 and p = 0.0133, respectively). Ang-2 levels significantly decreased at d15 only in arm A (p < 0.05 ). Plasma Ang-2 levels decreased in arm A and increased in arm B (p < 0.05 at all time points). There were no significant changes in other biomarker levels. Overall, decrease in Ang-2 levels from baseline to d57, was significantly associated with tumor downstaging (OR: 0.95, p < 0.0001).

Conclusions

Additional larger tailored studies are needed to corroborate the observed association between decreasing Ang-2 levels, tumoral downstaging and the role of Bevacizumab in this effect.

Disclosure

E. Aranda Aguilar: Consultant or Advisory Role: Roche and Merck Serono.

All other authors have declared no conflicts of interest.