Molecular-targeted therapy of head and neck squamous cell carcinoma: beyond cetuximab-based therapy

Cetuximab improves the overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN), in combination either with radiation therapy or with chemotherapy. However, only a minority of patients seem to benefit from cetuximab. This paper will review the different strategies developed either to overcome epidermal growth factor receptor (EGFR) resistance or to inhibit the other relevant activated molecular pathways.

Recent trials have investigated the possibility of including anti-EGFR therapies in the multimodal curative treatment of SCCHN in combination with neoadjuvant chemotherapy, concomitant chemoradiation or as maintenance therapy. Second-generation compounds (pan-HER or dual EGFR/HER-2 tyrosine kinase inhibitors) have been designed in an attempt to overcome the postulated resistance to anti-EGFR treatments in SCCHN. Alternative targeted therapies have also been developed to inhibit the other activated molecular pathways. Some of these new treatments have shown either promising activity in preclinical models or interesting preliminary activity in early phase II trials. Phase III trials are now required to validate the findings.

Despite an aggressive multimodal approach, more than 50% of patients with SCCHN will relapse. It is therefore essential that targeted agents continue to be evaluated in this disease in the hope of improving outcome.