Document Type
Article
Publication Date
8-1-2023
Abstract
BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).
METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Exploratory endpoints included the association of baseline programmed death-ligand 1 (PD-L1) expression as well as on-treatment changes in immune bias with treatment outcomes.
RESULTS: Twenty-four patients were enrolled. With a median follow-up of 36.1 months, grade 3 or higher treatment-related adverse events were reported in 21 individuals (88%); 5 individuals developed in-field soft tissue ulceration during consolidation immunotherapy, resulting in one fatality. The 3-year PFS and OS rates were 74% (95% CI 58% to 94%) and 96% (95% CI 88% to 100%), respectively. PD-L1 combined positive score (CPS) did not correlate with death or disease progression. Decreases in extracellular vesicle PD-L1 within the concurrent RIT phase were associated with prolonged PFS (p=0.006). Also, interval decreases in circulating interleukin (IL)4, IL9, IL12, and IL17a during concurrent RIT were associated with subsequent ulceration.
CONCLUSIONS: Definitive RIT with nivolumab and ipilimumab has sufficient clinical activity to support further development. Early changes in circulating biomarkers appear able to predict treatment outcomes as well as ensuing in-field soft tissue ulceration.
TRIAL REGISTRATION NUMBER: NCT03162731.
Recommended Citation
Johnson, Jennifer; Vathiotis, Ioannis A.; Harshyne, Larry; Ali, Ayesha; Bar-Ad, Voichita; Axelrod, Rita S.; Lorber, Emily; Curry, Joseph; Cognetti, David; Luginbuhl, Adam J.; Tuluc, Madalina; Keith, Scott W; Mahoney, M.G.; and Argiris, Athanassios, "Nivolumab and ipilimumab in combination with radiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck." (2023). Department of Medical Oncology Faculty Papers. Paper 247.
https://jdc.jefferson.edu/medoncfp/247
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
PubMed ID
37536941
Language
English
Comments
This article is the author's final published version in Journal for Immunotherapy of Cancer, Volume 11, Issue 8, August 2023, Article number e007141.
The published version is available at https://doi.org/10.1136/jitc-2023-007141.
Copyright © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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