1021PD - Modulation of the peritumoral microenvironment by cetuximab: a window pre-operative study in patients with squamous cell carcinoma of the head and n...

Date 30 September 2012
Event ESMO Congress 2012
Session Head and neck cancer
Topics Head and Neck Cancers
Translational Research
Presenter Sandra Schmitz
Authors S. Schmitz1, M. Hamoir2, H. Reychler3, M. Magremanne3, B. Weynand4, R. Lhommel5, F. Hanin5, D. Rommel6, N. Michoux6, J. Machiels7
  • 1Head And Neck Surgery, Cliniques universitaires Saint-Luc, 1200 - Brussels/BE
  • 2Head And Neck Surgery, Cliniques Universitaires St-Luc, 1200 - Brussels/BE
  • 3Maxillofacial Surgery, Cliniques universitaires Saint-Luc, 1200 - Brussels/BE
  • 4Anatomopathology, Cliniques Universitaires Saint-Luc, 1200 - Brussels/BE
  • 5Nuclear Medicine, Cliniques Universitaires St-Luc, 1200 - Brussels/BE
  • 6Radiology, Cliniques Universitaires Saint-Luc, 1200 - Brussels/BE
  • 7Medical Oncology, Cliniques Universitaires St. Luc, 01200 - Brussels/BE

Abstract

Background

Only a subset of SCCHN pts benefits from anti-EGFR mAbs. Trials with pre- and post-therapy tumor biopsies (windows studies) in treatment-naïve patients are crucial to better characterize the molecular pathways involved in treatment response or resistance.

Methods

Cetuximab (C) (400mg/m2 first wk followed by 250mg/m2/wk) was given pre-operatively during 2 wks (day -15 until day -1, 3 infusions) before surgery (day 0) to 20 treatment-naïve SCCHN pts selected for primary curative surgery. As controls, 5 additional pts were included without C treatment but with the same requirements regarding biopsies and imaging. Tumour biopsies, FDG/PET, and CT were performed at diagnosis and surgery. The aims of the study were (i) safety, (ii) C activity by FDG-PET (Po = 0.10, P1 = 0.35, a = 0.05 and b= 0.10) and (iii) translational research. We compared pathologic changes in surgical specimens of the C group with control specimens and correlated these results with microarray analysis performed on paired biopsies in the C group.

Results

C infusion given 24 hrs before surgery was safe. 90 % had a FDG-PET partial response (PR) (EORTC guideline) in the C group vs 0% in the controls. 52% had a ΔSUVmax decrease of >50%. In surgical specimens we detected modifications of the peritumoral environment. By immunochemistry, we found more fibrosis arranged in a compact manner in the C group than in the non-treated samples (histological score) (p = 0.04). Genome-wide expression analysis (Affymetrix HG U133 Plus 2.0) of the paired biopsies taken in the tumor center before and after C supports this histological observation. Results show a significant increase in expression (Student's T test p = 0.02; n = 20) of a previously published stroma signature (Finak et al., Breast Cancer Res 2006) after C. A trend was also observed between this stroma signature score and the fibrosis histological score.

Conclusions

Pre-operative study with C is safe. Our findings suggest that C induces quantitative modifications in the microenvironment of the tumor. We are currently investigating other components of the peri-tumoral environment (inflammation and vascularization).

Disclosure

J.P. Machiels: consultant/advisory role: Boehringer Ingelheim

All other authors have declared no conflicts of interest.