DAHANCA19: A randomized phase III study of primary curative (chemo)-radiotherapy and the EGFR-inhibitor zalutumumab for squamous cell carcinoma of the head and neck.

Abstract

Antibodies against the Epidermal Growth Factor receptor is suggested to decrease tumour failure and increase survival rates of patients (pts) with Head and Neck Squamous Cell Carcinomas (HNSCC) when combined with radiotherapy. This study aimed to evaluate if concurrent treatment with the EGFR inhibitor zalutumumab during (chemo-)radiotherapy improved outcome in pts with HNSCC. Overall, 608 eligible pts with biopsy-verified HNSCC of the oral cavity, pharynx and larynx were accrued November 2007 to June 2012. Pts were randomized to a control-arm of primary accelerated radiotherapy predominantly 66-68 Gy, 2 Gy/fraction, 6fx/week and concomitant daily hypoxic radiosensitisation with nimorazole. St. III-IV carcinomas received weekly cisplatin 40 mg/m² in addition to nimorazole. The zalutumumab-arm was identical to the control-arm plus zalutumumab 8 mg/kg. First dose was given the week before start of treatment and continued weekly during radiotherapy. Analyses were performed as intention-to-treat. Primary endpoint was loco-regional failure. Secondary endpoints were disease-specific survival and overall survival. In total, 307 pts were in the control-arm and 301 in the zalutumumab-arm. Median follow-up was 59 months. Patient and tumour parameters were well balanced. The 5-year loco-regional failure rate was 24 % in the zalutumumab-arm and 18 % in the control-arm; Hazard Ratio (HR) 1.16 (95 % CI 0.84-1.59); disease-specific survival; HR 1.04 (95 % CI 0.73-1.50) and overall survival; HR 1.21, (0.91-1.61). Effect of zalutumumab was not influenced by HPV/p16 status. Addition of concomitant zalutumumab to primary (chemo-)radiotherapy and concomitant nimorazole for HNSCC did not increase loco-regional control nor disease-specific or overall survival.