1. Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504
- Author
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Gillison, Maura L, Ferris, Robert L, Harris, Jonathan, Colevas, A Dimitrios, Mell, Loren K, Kong, Christina, Jordan, Richard C, Moore, Kevin L, Truong, Minh-Tam, Kirsch, Claudia, Chakravarti, Arnab, Blakaj, Dukagjin M, Clump, David A, Ohr, James P, Deeken, John F, Gensheimer, Michael F, Saba, Nabil F, Dorth, Jennifer A, Rosenthal, David I, Leidner, Rom S, Kimple, Randall J, Machtay, Mitchell, Curran, Walter J, Torres-Saavedra, Pedro, and Le, Quynh Thu
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Digestive Diseases ,Clinical Trials and Supportive Activities ,Rare Diseases ,Immunotherapy ,Radiation Oncology ,Dental/Oral and Craniofacial Disease ,Cancer ,Orphan Drug ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Humans ,Squamous Cell Carcinoma of Head and Neck ,Nivolumab ,Cisplatin ,Carcinoma ,Squamous Cell ,Mucositis ,Neoplasm Recurrence ,Local ,Head and Neck Neoplasms ,Fatigue ,Other Physical Sciences ,Oncology & Carcinogenesis ,Oncology and carcinogenesis ,Theoretical and computational chemistry ,Medical and biological physics - Abstract
PurposeProgrammed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown.Methods and materialsWe evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting toxicity (DLT). If ≤2 of the first 8 evaluable patients experienced a DLT, an arm was considered safe. Secondary endpoints included toxicity and feasibility of adjuvant nivolumab to 1 year, defined as all 7 additional doses received by ≥4 of the first 8 evaluable patients across arms.ResultsOf 39 patients (10 in arms 1, 3, 4 and 9 in arm 2), 72% had T3-4 tumors, 85% had N2-3 nodal disease, and 67% had >10 pack-years of smoking. There were no DLTs in arms 1 and 2, 1 in arm 3 (mucositis), and 2 in arm 4 (lipase elevation and mucositis in 1 and fatigue in another). The most common grade ≥3 nivolumab-related adverse events were lipase increase, mucositis, diarrhea, lymphopenia, hyponatremia, leukopenia, fatigue, and serum amylase increase. Adjuvant nivolumab was feasible as defined in the protocol.ConclusionsConcomitant nivolumab with the 4 tested regimens was safe for patients with intermediate- and high-risk HNSCC, and subsequent adjuvant nivolumab was feasible as defined (NCT02764593).
- Published
- 2023