Avelumab-cetuximab-radiotherapy versus standards of care in locally advanced squamous-cell carcinoma of the head and neck: The safety phase of a randomised phase III trial GORTEC 2017-01 (REACH)

Background: Based on the hypothesis of synergistic effect of avelumab with cetuximab and radiotherapy, this new combination is tested in a randomised trial against two well-established standard of care (SOC) in locally advanced squamous-cell carcinoma of the head and neck (LA-SCCHN). Methods: This phase III trial comprises two cohorts of patients deemed fit to receive cisplatin (100 mg/m(2) Q3W) (cohort 1) or unfit to cisplatin (cohort 2). The SOC was Intensity Modulated Radiation Therapy (IMRT) with cisplatin in cohort 1 (arm A) and with weekly cetuximab in cohort 2 (arm D). In both cohorts, experimental arms (arms B and C) were IMRT with cetuximab and avelumab (10 mg/kg day 7 and every 2 weeks) followed by avelumab every two weeks for 12 months. A safety phase was planned among the first 41 patients in experimental arms by monitoring grade >= IV adverse events (AEs) with an unacceptable rate of 35%. Results: Between September 2017 and August 2018, 82 patients with LA-SCCHN were randomised including 41 patients in experimental arms. All patients of experimental arms except one (arm C) received entire radiotherapy as planned. Most common grade >= III AEs were mucositis, radio-dermatitis, and dysphagia. Grade >= IV AEs occurred in 5/41 (12%) patients, all in arm C (no grade V). This rate was acceptable according to the hypotheses of the safety phase. In the SOC arms, grade >= IV AEs occurred in 3/21 patients (14%) in arm A and 2/20 (10%) in arm D. One grade V haemorrhage occurred in arm A. Conclusion: The avelumab-cetuximab-RT combination was tolerable for patients with LA-SCCHN, and the approval was given for continuing the trial without modification. (C) 2020 The Author(s). Published by Elsevier Ltd.