xRead - An Update on Immunotherapy in Head and Neck Cancer (November 2025)
Pembrolizumab in Head and Neck Cancer
de Pesquisa em Oncologia, Hospital Nossa Senhora de Con ceição, Porto Alegre, Brazil; 13 Royal Brisbane and Women’s Hospital, University of Queensland, Brisbane, Australia; 14 In stitut Català d’Oncologia L’Hospitalet, Institut d’Investigació Biomèdica de Bellvitge, Barcelona; 15 Centro Regional Integrado de Oncologia, Fortaleza, Brazil; 16 Hiroshima University Hospi tal, Hiroshima, Japan; 17 Maria Sklodowska-Curie National Re search Institute of Oncology Gliwice Branch, Gliwice, Poland; 18 Department of Otorhinolaryngology, University of Lübeck, Lübeck, Germany; 19 Department of Otolaryngology, Head and Neck Surgery, University Hospital Tübingen, Tübingen, Ger many; 20 Department of Medicine I, Division of Oncology, Med ical University of Vienna, Vienna; 21 Department of Otorhinolar yngology and Head and Neck Surgery, Ulm University Medical
Center and Comprehensive Cancer Center Ulm, Ulm, Germany; 22 Yokohama City University School of Medicine, Yokohama, Ja pan; 23 Hadassah Medical Center, Jerusalem; 24 Geneva Univer sity Hospital, University of Geneva, Geneva; 25 National Cancer Institute, Kyiv, Ukraine; 26 Hospital CUF Descobertas, Lisbon, Portugal; 27 Rutgers Cancer Institute, Newark, NJ; 28 Division of Hematology–Oncology, Department of Medicine, Rutgers New Jersey Medical School, Newark; 29 Fred Hutchinson Cancer Center, University of Washington, Seattle; 30 Providence Cancer Institute, Earle A. Chiles Research Institute, Portland, OR; 31 Merck, Rahway, NJ; 32 Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Washington University School of Medicine, Alvin J. Siteman Cancer Center, and Barnes–Jewish Hospital, St. Louis.
References 1. National Comprehensive Cancer Net work. NCCN clinical practice guidelines in oncology: head and neck cancers. Version 3.2025. (https://www.nccn.org/guidelines/ guidelines-detail?category=1&id=1437). 2. Machiels J-P, René Leemans C, Golusin ski W, et al. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hy popharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020;31:1462-75. 3. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or with out concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945-52. 4. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-44. 5. Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of stan dard radiation therapy and two schedules of concurrent chemoradiotherapy in pa tients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003; 21:92-8. 6. Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: a comparative anal ysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005;27:843-50. 7. Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemo therapy versus cetuximab with chemo therapy for recurrent or metastatic squa mous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 2019;394:1915-28. 8. Choueiri TK, Tomczak P, Park SH, et al. Overall survival with adjuvant pembro lizumab in renal-cell carcinoma. N Engl J Med 2024;390:1359-71. 9. Schmid P, Cortes J, Dent R, et al. Overall survival with pembrolizumab in
early-stage triple-negative breast cancer. N Engl J Med 2024;391:1981-91. 10. Lorusso D, Xiang Y, Hasegawa K, et al. Pembrolizumab or placebo with chemo radiotherapy followed by pembrolizumab or placebo for newly diagnosed, high risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2024;404:1321-32. 11. Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early stage non–small-cell lung cancer. N Engl J Med 2023;389:491-503. 12. Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 2018;378:1789-801. 13. Uppaluri R, Campbell KM, Egloff AM, et al. Neoadjuvant and adjuvant pembro lizumab in resectable locally advanced, human papillomavirus–unrelated head and neck cancer: a multicenter, phase II trial. Clin Cancer Res 2020;26:5140-52. 14. Wise-Draper TM, Gulati S, Palackdhar ry S, et al. Phase II clinical trial of neo adjuvant and adjuvant pembrolizumab in resectable local-regionally advanced head and neck squamous cell carcinoma. Clin Cancer Res 2022;28:1345-52. 15. Oliveira G, Egloff AM, Afeyan AB, et al. Preexisting tumor-resident T cells with cytotoxic potential associate with re sponse to neoadjuvant anti-PD-1 in head and neck cancer. Sci Immunol 2023;8(87): eadf4968. 16. Maurer W, Bretz F. Multiple testing in group sequential trials using graphical approaches. Stat Biopharm Res 2013;5: 311-20 (https://www.tandfonline.com/doi/ abs/10.1080/19466315.2013.807748). 17. Schmid P, Cortes J, Pusztai L, et al. Pem brolizumab for early triple-negative breast cancer. N Engl J Med 2020;382:810-21. 18. Machiels JP, Tao Y, Licitra L, et al. Pembrolizumab plus concurrent chemo radiotherapy versus placebo plus concur
rent chemoradiotherapy in patients with locally advanced squamous cell carcino ma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial. Lancet Oncol 2024;25:572-87. 19. Lee NY, Ferris RL, Psyrri A, et al. Avel umab plus standard-of-care chemoradio therapy versus chemoradiotherapy alone in patients with locally advanced squa mous cell carcinoma of the head and neck: a randomised, double-blind, placebo controlled, multicentre, phase 3 trial. Lan cet Oncol 2021;22:450-62. 20. Tao Y, Biau J, Sun XS, et al. Pembroliz umab versus cetuximab concurrent with radiotherapy in patients with locally ad vanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, ran domized, phase II trial. Ann Oncol 2023; 34:101-10. 21. Tao Y, Auperin A, Sun X, et al. Avel umab-cetuximab-radiotherapy (RT) versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): final analysis of randomized phase III GORTEC 2017-01 REACH trial. Ann Oncol 2024;35:Suppl 2: S616 (https://www.annalsofoncology.org/ article/S0923-7534(24)02434-7/fulltext). 22. Wong DJ, Fayette J, Teixeira M, et al. Abstract CT009: IMvoke010: a phase III, double-blind randomized trial of atezoliz umab (atezo) after definitive local therapy vs placebo in patients (pts) with high-risk locally advanced (LA) squamous cell car cinoma of the head and neck (SCCHN). Cancer Res 2024;84:Suppl 7:CT009 (https:// aacrjournals.org/cancerres/article/84/7 _Supplement/CT009/742401/Abstract -CT009-IMvoke010-A-phase-III-double -blind). 23. Sava J. Post-operative nivolumab sig nificantly improves DFS in head and neck cancer. Targeted Oncology, January 10, 2025 (https://www.targetedonc.com/view/ post-operative-nivolumab-significantly -improves-dfs-in-head-and-neck-cancer).
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