A Randomized Phase II Translational Research Study in Patients with Advanced Head and Neck Cancer to Investigate the Effects of Standard Chemoradiation and Add-on Concurrent Epidermal Growth Factor Receptor (EGFR) Inhibitor ± Consolidation EGFR Inhibitor

Preclinical data suggest that cetuximab should be continued after end of concurrent RT/cetuximab due to its efficacy against residual tumor cells and angiogenesis in the irradiated tumor niche. Based on this concept the phase II add-on cetuximab (AOC) study was designed. Altogether 59 patients with advanced head and neck cancer, stages T3-4 Nx or Tx N2b-c, were treated with radiochemotherapy (70 Gy, cisplatin 40mg/m2 weekly) in combination with concurrent cetuximab (loading dose 400mg/m2, then 250mg/m2 weekly). Thereafter patients were randomized to cetuximab consolidation (500 mg/m2 biweekly x 6) or no further treatment. The primary endpoint was the 2-year locoregional control (LRC) rate. As translational research endpoints serum markers were analyzed before and during treatment and CT-based quantitative image analysis (radiomics) of the 3D primary tumor volume was performed. The 2-year LRC rates were 67.9% and 67.7% in the treatment arms with and without consolidation cetuximab. Higher than median levels prior to treatment of three serum markers were negatively associated with the 2-year LRC rate in the overall patient cohort: Osteopontin, IL8 and FasL2 (p<0.05). A radiomics model consisting of 2 radiomic features could be built showing that higher entropy and higher complexity of tumor Hounsfield unit distribution indicates worse LRC (CI 0.66). No correlation was found between biological and imaging markers. Consolidation cetuximab does not improve LRC when continued after end of RCT/cetuximab. Independent prognostic biological and imaging markers could be identified for the overall patient cohort. Studies with larger patient numbers are needed to identify the biological basis of imaging features.