Immuno-radiotherapy with cetuximab and avelumab for advanced stage head and neck squamous cell carcinoma: Results from a phase-I trial. (January 2020)

• Record Type: Journal Article
• Authors: Elbers, Joris B.W.; Al-Mamgani, Abrahim; Tesseslaar, Margot E.T.; van den Brekel, Michiel W.M.; Lange, Charlotte A.H.; van der Wal, Jacqueline E.; Verheij, Marcel; Zuur, Charlotte L.; de Boer, Jan Paul
• Is Part Of: Radiotherapy and oncology. Volume 142(2020)
• Page Start: 79
• Page End: 84
• Publication Date: 2020-01
• Subjects: Immunotherapy -- Radiotherapy -- Head and neck squamous cell carcinoma -- PD-L1 -- Avelumab -- Cetuximab; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2019.08.007
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: Feasibility trial of standard of care radiotherapy plus a PD-L1 inhibitor for HNSCC. Immune-related toxicity was manageable and transient. Radiotherapy-related toxicity was in accordance with standard of care. Cetuximab-RT plus avelumab is feasible; data provide ground for efficacy trials. Abstract: Background and purpose: Radiotherapy (RT) with cetuximab is an alternative for advanced-stage head and neck squamous cell carcinoma (HNSCC) patients who are unfit for cisplatin treatment. As 5-year overall survival is below 50%, it is of interest to test PD-L1 immune checkpoint blockade (avelumab) with cetuximab-RT in the curative setting. Materials and methods: Phase-I feasibility trial (planned n = 10, NCT02938273) of conventional cetuximab-RT with avelumab (concurrent 10 mg/kg Q2W + 4 months maintenance) for advanced-stage HNSCC patients unfit for cisplatin treatment. Results: One of ten included patients experienced grade 2 cetuximab-related infusion reaction and withdrew from the study before avelumab was administered. One patient discontinued treatment after 2 courses of avelumab and 12×2Gy RT for personal reasons. In 2/8 remaining patients, avelumab was stopped after 4 and 8 courses because of toxicity and tumor progression, respectively. There was no grade 4–5 toxicity. Grade 3 immune-related toxicity was manageable and occurred in 4 patients. One patient was treated with topical steroids for grade 3 maculopapular rash and 3 patients received high-dose prednisone for grade 3 elevated liver enzymes ( n = 1) and pneumonitis ( n = 2). Seven patients experienced grade 3 RT-related toxicity with no severe specific cetuximab-related toxicity. Tumor recurrence occurred in 4/8 patients (50%) after a median of 12 (8–26) months follow-up. Conclusion: Cetuximab-RT plus avelumab is feasible in patients with advanced-stage HNSCC who are unfit for cisplatin treatment. Immune-related toxicity was transient and manageable and radiotherapy-related toxicity was in accordance with standard of care. This pilot study provides grounds for larger efficacy trials.