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Editorial
. 2025 Dec 31;14(12):8221-8227.
doi: 10.21037/tcr-2025-2042. Epub 2025 Dec 23.

Implementing perioperative immunotherapy for head and neck cancer after KEYNOTE-689: questions and challenges

Brianna Brammer  1   2 , Jennifer H Gross  1   2 , Brian J Boyce  1   2 , Nabil F Saba  2   3 , Nicole C Schmitt  1   2
Affiliations
Editorial

Implementing perioperative immunotherapy for head and neck cancer after KEYNOTE-689: questions and challenges

Brianna Brammer et al. Transl Cancer Res. .
No abstract available

Keywords: Head and neck cancer; immunotherapy; neoadjuvant; pembrolizumab.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-2042/coif). J.H.G. is a consultant for Acera Surgical and has given lectures on their behalf; and was an institutional PI for a multi-institutional clinical trial sponsored by the University of Arizona. N.F.S. reports paid or unpaid consulting for Astra Zeneca, Eisai Medical, Exelixis, Merck, Merck EMD Serono, Pfizer, Kura, Vaccinex, CUE, BionTech, GSK, TOSK, Seagen, Flamingo, Infinity, Inovio, Aveo, Medscape, Onclive, Uptodate, BMS, J&J, JohnsonCornerstone, Celldex, Surface Oncology, Urogen, Summit, Guidepoints, Astex, Imugene, Faron Pharmaceutical, Coherus, Adagene, Fulgent, Reddy Laboratories, Springer, Nanobiotix, and Taiho, as well as research funding from National Institutes of Health, Exelixis and Bristol Myers Squibb. N.C.S. reports paid consulting for GeoVax, Aspargo Labs, Inc., Johnson & Johnson, and Regeneron, as well as funding from National Institutes of Health and Taiho Oncology. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Overview of KEYNOTE-689 study design and results. CPS, combined positive score; CRT, chemoradiation therapy; HNSCC, head and neck squamous cell carcinoma; RT, radiation therapy.
Figure 2
Figure 2
Schematic of pembrolizumab mechanism of action. Created with Biorender.com. (A) Schematic of pembrolizumab mechanisms of action in head and neck cancer; (B) pembrolizumab re-invigorates T cell activation and effector functions; (C) treatment with pembrolizumab causes a proliferative burst of stem-like T cells. HNSCC, head and neck squamous cell carcinoma; IFN-γ, interferon gamma; MHC, major histocompatibility complex; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1.
See this image and copyright information in PMC

Comment on

  • Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer.
    Uppaluri R, Haddad RI, Tao Y, Le Tourneau C, Lee NY, Westra W, Chernock R, Tahara M, Harrington KJ, Klochikhin AL, Braña I, Vasconcelos Alves G, Hughes BGM, Oliva M, Pinto Figueiredo Lima I, Ueda T, Rutkowski T, Schroeder U, Mauz PS, Fuereder T, Laban S, Oridate N, Popovtzer A, Mach N, Korobko Y, Costa DA, Hooda-Nehra A, Rodriguez CP, Bell RB, Manschot C, Benjamin K, Gumuscu B, Adkins D; KEYNOTE-689 Investigators. Uppaluri R, et al. N Engl J Med. 2025 Jul 3;393(1):37-50. doi: 10.1056/NEJMoa2415434. Epub 2025 Jun 18. N Engl J Med. 2025. PMID: 40532178 Clinical Trial.

References

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    1. Uppaluri R, Haddad RI, Tao Y, et al. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer. N Engl J Med 2025;393:37-50. 10.1056/NEJMoa2415434 - DOI - PubMed
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