58IN - The importance of window of opportunity studies

Date 01 October 2012
Event ESMO Congress 2012
Session Biologically based treatment in head and neck squamous cell carcinoma
Topics Anti-Cancer Agents & Biologic Therapy
Head and Neck Cancers
Presenter Jean-Pascal Machiels
Authors J. Machiels1, S. Schmitz2
  • 1Medical Oncology, Cliniques Universitaires St. Luc, 01200 - Brussels/BE
  • 2Head And Neck Surgery, Cliniques universitaires Saint-Luc, Brussels/BE

Abstract

One way to better understand the molecular activity of a particular treatment is to perform trials with collection of pre- and post-treatment tumor biopsies. Squamous cell carcinoma of the head and neck (SCCHN) represents an attractive disease for this approach because these tumors are generally easily accessible to iterative biopsies. We performed trials investigating figitumumab and sunitinib in recurrent and/or metastatic SCCHN after platinum failure. Pre-and post- treatment biopsies could be obtained in some patients. However, this trial design has some major limitations in regard of translational research. First, most patients have received radiation and/or chemotherapy and/or surgery, and so have developed multifactorial resistance and are less likely to respond to new agents and, second, feasibility of conducting translational research is hampered by ethical considerations in obtaining iterative tumor biopsies in palliative patients. One way to resolve some of these issues is to perform “window” studies where a targeted agent is given during the incompressible period of time between the diagnosis and surgery in patients selected for a primary surgical treatment. Evaluation of compounds in the pre-operative window setting could maximize the chance of observing tumor response. In addition, the collection of biopsies before treatment and after treatment may provide insights into the pharmacodynamic effects of novel agents as well as their mechanisms of action and also help to identify some hypotheses regarding treatment resistance. In SCCHN, the EGFR and its downstream molecular pathways are crucial and EGFR overexpression is linked with poor prognosis. Cetuximab combined with RT or CT improves survival. However, only a minority of patients benefits from anti-EGFR mAbs. We designed trials to investigate the safety, molecular and imaging response of anti-EGFR treatments in the window pre-operative study in SCCHN. Briefly, the anti-EGFR drug was given during two weeks before surgery. 18FDG-PET, CT-scan or MRI, tumor biopsies, and plasma collection were taken before and after treatment. We demonstrated the safety and feasibility of this approach. Biological samples are currently analyzed to better understand the molecular mechanisms involved.

Disclosure

J.P. Machiels: Advisory role for Boerhinger Research grant from Sanofi All other authors have declared no conflicts of interest.