Interview with Ezra Cohen, MD
Associate Professor of Medicine
University of Chicago Medical Center
01.10.2011Q. What are the current treatment options for head and neck cancer?
A. It's truly a very stage-based cancer, as many cancers are. For early stage disease, we are usually going to invoke a single modality, surgery or radiation therapy and for the majority of patients there we expect them to be cured. 80-90% cure rate. For locally advanced disease, and I use that term to describe either stage 3 or stage 4, patients who have either a larger tumour or lymph node involvement and for those patients we are really now talking about multi-modality therapy; surgery, radiation and chemotherapy combined or sequenced in one form or another to deliver the best curative options possible.
Q. What role does research into targeted agents for head and neck cancer play?
A. In terms of targeted agents, that's certainly an area of research that we've been involved in for some time and continue to be involved in. I would say the primary target that's been successful in head and neck cancer has been the epidermal growth factor receptor or EGFR. We know that EGFR is expressed at high levels in these cancers, in fact it's universally expressed in squamous cell carcinoma of the head and neck. We know that its expression is linked with prognosis so the higher the expression of EGFR, the worse the prognosis. And we know that inhibiting EGFR at least in the laboratory does what we want it to do. It slows growth, it slows metastasis, it inhibits blood vessel growth and so with all that in mind EGFR inhibitors were naturally explored in head and neck cancer and in fact they have been successful leading to at least the approval of one such drug, cetuximab.
Q. What role does EGFR inhibition play in targeted agents for head and neck cancer?
A. The epidermal growth factor receptor has three other family members, EGFR is also called ErbB1. The other family members are imaginatively called ErbB2, 3 and 4. And there are agents currently in investigation that can inhibit all four of the family members which may be relevant to head and neck cancer. For agents that can inhibit all four of the family members, there have been some very interesting results and there's one agent in particular that's now in development and in fact in large Phase III trials that obviously we hope will move forward and that is afatinib*. Afatinib* is a small molecule inhibitor of all four of the family members of the EGFR system. It binds to EGFR, to HER2 and to ErbB4. HER3 does not have a tyrosine kinase domain. It needs to bind with its other family members, what we call dimerisation, in order to become activated, so if you have an agent that inhibits 1, 2 and 4, it effectively also inhibits 3. We know that in head and neck cancer and in fact in some other cancers where EGFR plays an important role, that the dimerisation of these receptors is critical for activation and in fact the dimerisation that is most activating of signalling pathways is not two similar partners so two EGFR molecules but it's EGFR and one of its other family members such as HER2, HER3 or HER4, and so we think that inhibiting all four family members would be more effective than EGFR alone. What we've seen so far is quite promising data for afatinib* in head and neck cancer. There was a randomised trial completed that compared afatinib* to a monoclonal antibody directed against EGFR called cetuximab and what it showed was that afatinib* is at least comparably effective as cetuximab if not perhaps a little bit better.
*Afatinib is an investigational compound. Its safety and efficacy have not yet been fully established.