Abstract

PURPOSE: Programmed death-1 immune checkpoint blockade (PD-1 ICB) 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 HNSCC patients remain unknown.METHODS AND MATERIALS: We evaluated the safety of nivolumab concomitant with 70Gy intensity-modulated radiotherapy and weekly cisplatin (arm 1), every three-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4), in newly diagnosed intermediate or high-risk local-regionally advanced HNSCC. Patients received nivolumab from two weeks prior to three months post radiotherapy. The primary endpoint was dose-limiting toxicity (DLT). If = 2 of the first 8 evaluable patients experience a DLT, an arm was considered safe. Secondary endpoints included toxicity and feasibility of adjuvant nivolumab to one year, defined as all 7 additional doses received by =4 of the first 8 evaluable patients across arms.RESULTS: Of 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 one 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.CONCLUSIONS: Concomitant nivolumab with the four tested regimens was safe for patients with intermediate and high-risk HNSCC and subsequent adjuvant nivolumab was feasible as defined (NCT# xxxx).

View details for DOI 10.1016/j.ijrobp.2022.10.008

View details for PubMedID 36228746