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)
Yungan Tao, Anne Aupérin, Xushan Sun, Christian Sire, Laurent Martin, Alexandre Coutte, Cedrik Lafond, Jessica Miroir, Xavier Liem, Frederic Rolland, Caroline Even, France Nguyen, Esma Saada, Aline Maillard, Natacha Colin-Batailhou, Juliette Thariat, Joël Guigay, Jean Bourhis, Yungan Tao, Anne Aupérin, Xushan Sun, Christian Sire, Laurent Martin, Alexandre Coutte, Cedrik Lafond, Jessica Miroir, Xavier Liem, Frederic Rolland, Caroline Even, France Nguyen, Esma Saada, Aline Maillard, Natacha Colin-Batailhou, Juliette Thariat, Joël Guigay, Jean Bourhis
Abstract
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/m2 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. CLINICALTRIAL.GOV: NCT02999087.
Keywords: Avelumab-cetuximab-radiotherapy; Head and neck; Locally advanced squamous cell carcinoma; Safety phase.
Conflict of interest statement
Conflict of interest statement All authors declare no conflict of interest.
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Source: PubMed