Joris B W Elbers1, Abrahim Al-Mamgani2, Margot E T Tesseslaar3, Michiel W M van den Brekel4, Charlotte A H Lange5, Jacqueline E van der Wal6, Marcel Verheij2, Charlotte L Zuur4, Jan Paul de Boer7. 1. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 2. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 3. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 4. Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 5. Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 6. Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 7. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: j.d.boer@nki.nl.
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.
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.