Head and neck cancer, mostly of squamous cell origin, accounts for roughly 6% of all cases of cancer, and nearly two thirds of these patients present with advanced disease (stages III and IV) which has a poor prognosis. Dr. John Bean, EORTC Medical Science Writer, recently interviewed Prof. Jean-Pascal Machiels of the Cliniques Universitaires St. Luc, Université catholique de Louvain, Brussels, and Prof. Cedric Blanpain of the Interdisciplinary Research Institute at the Université Libre de Bruxelles concerning an EORTC window study concept in which pre-operative new agents are investigated in patients with squamous cell carcinoma of the head and neck (SCCHN) selected for a primary surgical treatment. A first new agent, a pan HER inhibitor, is already being studied with patients currently on treatment.
Dr. John Bean, EORTC Medical Science Writer (JB): Professor Machiels, as Coordinator, could you describe the general premise for this study?
Pr. Machiels: The treatment of SCCHN depends on the site and the stage of the tumor and can include surgery, radiotherapy, chemotherapy, and anti-EGFR treatment. This is a very aggressive multimodal treatment, yet in spite of this more than half of these patients will suffer a relapse. Currently, the choice of treatment is based on the anatomy and morphology of the tumor rather than on its biology. For example, only a minority of patients treated with an anti-EGFR therapy will respond to this therapy and we have no biomarkers able to identify these patients. Studies to approach the molecular mechanisms of new compounds and also to identify molecular parameters are needed to personalize each patient’s cancer treatment.
JB: This is certainly a complex disease. How will this study help us to identify the patients most likely to respond to the targeted therapy?
Pr. Machiels: Tumor biopsies and plasma will be collected at different time points during the treatment of our patients. We have also included an imaging component in this EORTC study, which will correlate results from imaging studies (Fluorodeoxyglucose – positron emission tomography/computed tomography and magnetic resonance imaging) with the molecular analyses. This is extremely important to develop a better understanding of the molecular mechanisms involved in squamous cell carcinoma of the head and neck and treatment activity: we want to know how agents act on the intended target molecular pathways and also investigate suspected resistance mechanisms.
I should also point out that a research sub-study is comparing the activity of tested agents in mice, bearing human squamous cell carcinoma of the head and neck xenografts with its activity in patients with the disease. This is a unique partnership between the Université libre de Bruxelles, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, and the EORTC, where combined expertise can help us understanding resistance and possibly plan further treatments.
JB: How will this EORTC sub-study help us find a better treatment?
Prof. Blanpain: This sub-study has two very important objectives. First, we want to assess whether response to new agents in SCCHN mice xenografts is comparable to that in patients.
Secondly, and keeping in mind what Dr. Machiels said earlier about the development of multifactorial resistance in patients with SCCHN who received multimodal treatment, we want to identify the tumor cells that are the root cause of this resistance.
The results of these studies will enable us to conduct a larger trial that would allow us to confirm or validate the generated hypotheses.
JB: How will the translational research studies with the mice xenografts help you to improve treatments for patients with SCCHN?
Prof. Blanpain: The results of these translational research studies could help us to tailor the treatment for individual cancer patients. We hope that in the future such kind of studies will be helpful to predict which patients SCCHN would be most likely to respond to targeted therapy. We could identify the most suitable drug combination to achieve the best clinical response.
This research would also improve our understanding mechanism of action of new agents as well as the evasion mechanisms. We might also uncover pathways which might be implicated in the resistance of this cancer to therapy. So, this research could well identify the cell of origin to therapeutic resistance and an understanding of the mechanisms regulating drug resistance and relapse in SCCHN.
JB: This study offers hope for improving treatments for patients with SCCHN. Could you tell us how many patients will be included in this trial and in which countries it will be conducted?
Pr. Machiels: The first study, EORTC 90111-24111, plans to include 30 patients with newly diagnosed and histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, and 25 of these patients will be randomized into the afatinib arm. This study is coordinated by the EORTC Head and Neck Cancer Group and is being conducted in three sites in two countries: Belgium and Italy. It is an academic study supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC) Investigator Grant 10173, UCL/Cliniques Universitaires Saint-Luc, and an educational grant from Boehringer Ingelheim.
JB: The EORTC welcomes such partnership which promotes Belgium to the fore front of clinical research. The infrastructure and Headquarters of the EORTC as a unique pan European platform joined to two highly visible clinical and research units is a novel model of cooperation to address the complex biology of cancer.
About the Université Libre de Bruxelles
Located in the heart of Europe, Université Libre de Bruxelles is a multicultural university with one third of students and researchers from abroad. Its outward-looking position with regard to Europe and the world has resulted in a number of agreements, collaborations and special partnerships being set up with some of the world’s top universities.
Three Nobel Prizes, one Fields Medal, three Wolf Prizes and two Marie Curie Prizes are further evidence of the University’s longstanding tradition of excellence. The Université Libre de Bruxelles is an active member of the Research Area and is involved in almost 130 projects financed by the 7th European Framework Programmes. Over the past few years, it has obtained seven starting Grants from the European Research Area to finance research in Medicine, Economics, Mathematics, Sociology, or Political Science, as well as two Advanced Grants in Artificial Intelligence and Physics. In addition, the University’s Institute for European Studies is recognized as a “Jean Monnet European research centre” for its work on European integration.
The Université Libre de Bruxelles has 13 faculties, schools and specialized institutes that cover all the disciplines, closely combining academic input and research. It offers almost 40 undergraduate programs and 235 graduate programs. It also partners 20 Doctoral schools with almost 1,600 PhD in progress.
About the cliniques universitaires Saint-Luc and the Université catholique de Louvain (UCL), Brussels
The Cliniques universitaires Saint-Luc Cancer Centre is the largest oncology center in Brussels and in the French-speaking part of Belgium, treating all types of adult and childhood cancers.
Cliniques universitaires Saint-Luc is the academic hospital of the Université catholique de Louvain (UCL).Saint-Luc and partners provide state-of-the-art local care of reliable high quality. They set the benchmark for some complex pathologies in Belgium and internationally. They deliver excellence in the fulfillment of their university missions of research, innovation and teaching, which they share with UCL.
Founded in 1425, UCL is one of Europe’s oldest universities, with 28,840 students on six sites: Louvain-la-Neuve, Brussels (Woluwe and Saint-Gilles), Mons, Tournai, and Charleroi. In the 2012 QS World University Rankings, UCL was ranked 127th, making it Belgium’s leading French-speaking university. UCL educates almost every other French-speaking Belgian, and attracts every year 5,000 international students from around the globe (a number of UCL‘s programs are taught in English). UCL is also the first French-speaking university in Europe to offer courses (in French and English) on the on-line platform edX. UCL trains students in all disciplines, from beginner’s level through doctorate and on to adult continuing education. With one Nobel Prize, 21 Francqui Prizes (“the Belgian Nobel”) and numerous international awards, teaching at UCL is based on solid research and innovation, with a lot of applications for society (50 spin-offs and 197 enterprises in the three scientific parks of the university). UCL is also one of the 22 European universities to have received the ECTS label, an EU recognition of the quality of its management of international exchanges.
About the EORTC
Founded in 1962, the European Organisation for the Research and Treatment of Cancer (EORTC) brings together European cancer clinical research experts from all disciplines for trans-national collaboration.
Both multinational and multidisciplinary, the EORTC Network comprises more than 2,000 collaborators from all disciplines involved in cancer treatment and research in more than 300 hospitals in over 30 countries.
Through translational and clinical research, the EORTC offers an integrated approach to drug development, drug evaluation programs and medical practices.
EORTC Headquarters, a unique pan European independent clinical research infrastructure, is based in Brussels, Belgium, from where its various activities are coordinated and run.
For more information concerning EORTC trial 90111-24111 please contact: www.eortc.org/contact
John Bean, PhD
EORTC Medical Science Writer