Gillison ML, Ferris RL, Harris J, Colevas AD, Mell LK, Kong C, Jordan RC, Moore KL, Truong MT, Kirsch C, Chakravarti A, Blakaj DM, Clump DA, Ohr JP, Deeken JF, Gensheimer MF, Saba NF, Dorth JA, Rosenthal DI, Leidner RS, Kimple RJ, Machtay M, Curran WJ, Torres-Saavedra P, Le QT
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).