JS3 Keynotespeech THE ROLE OF ANTI-EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODIES IN HEAD AND NECK CANCER

Over 90% of head and neck cancer patients express the epidermal growth factor receptor (EGFR) and the degree of overexpression has been correlated with patient prognosis. The anti-EGFR-directed antibody cetuximab has been shown to have single-agent activity in the recurrent disease setting. Response rates range around 10%–15% with no predictive factors identified to date. Given this modest single agent activity, investigations have focused on adding cetuximab to established standard therapy. In patients with recurrent disease, a study adding cetuximab to standard platinum and 5-FU doublet chemotherapy showed a statistically significant increase in median survival leading to approval of the triple drug regimen in the United States. A second randomized trial evaluated the addition of cetuximab to standard radiation therapy versus radiation therapy alone in previously untreated patients with locoregionally advanced disease and also showed a statistically significant increase in survival. Thus, cetuximab can be viewed as an alternative standard therapy to either induction chemotherapy or concurrent chemoradiotherapy. A recently completed randomized trial compared standard cisplatin plus radiation therapy with the same chemoradiotherapy regimen plus cetuximab. Surprisingly, no benefit was seen. Thus, the addition of cetuximab to cisplatin-based chemoradiotherapy results in increased toxicity without further outcome benefits. No predictive biomarkers are available and identification of optimal patient groups for this approach has not been possible to date. In particular, the role of cetuximab-enhanced radiation in HPV-related tumors remains unclear. A current study in patients with HPV-positive head and neck cancer is comparing cetuximab and radiation with chemoradiotherapy.