Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504

Authors

Maura L Gillison
Robert L Ferris
Jonathan Harris
A Dimitrios Colevas
Loren K Mell
Christina Kong
Richard C Jordan
Kevin L Moore
Minh-Tam Truong
Claudia Kirsch
Arnab Chakravarti
Dukagjin M Blakaj
David A Clump
James P Ohr
John F Deeken
Michael F Gensheimer
Nabil F Saba
Jennifer A Dorth
David I Rosenthal
Rom S Leidner
Randall J Kimple
Mitchell Machtay
Walter J Curran
Pedro Torres-Saavedra
Quynh Thu Le

Publication Date

3-15-2023

Journal

International Journal of Radiation, Oncology, Biology, Physics

Abstract

PURPOSE: Programmed 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 MATERIALS: We 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.

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 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.

CONCLUSIONS: Concomitant 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).

Keywords

Humans, Squamous Cell Carcinoma of Head and Neck, Nivolumab, Cisplatin, Carcinoma, Squamous Cell, Mucositis, Neoplasm Recurrence, Local, Head and Neck Neoplasms, Fatigue

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Supplementary Materials

PMID: 36228746