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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Head and Neck Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1577509
This article is part of the Research Topic Pathophysiology and Therapeutic Strategies for Oral and Head and Neck Cancers View all 6 articles
Real World Treatment Patterns for Recurrent and Metastatic Head & Neck Cancer in the post-KEYNOTE 048 Era
Provisionally accepted
Daniel Younghoon Lee *
Alexander Pan 
Maxim Yaskolko Michael Chiorazzi 
Aarti Bhatia 
Barbara Burtness 
Jeffrey Ishizuka *- Cancer Center, School of Medicine, Yale University, New Haven, Connecticut, United States
Background While KEYNOTE-048 established anti-PD1 with or without chemotherapy as first-line treatment for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) with combined positive score (CPS) ≥ 1, treatment choice remains ambiguous given additional toxicity of combination treatment.Methods Patients treated first-line with anti-PD1 monotherapy, anti-PD1+chemotherapy, or cetuximab+chemotherapy in the Flatiron Health database were included. Treatment group differences were assessed with chi-squared and t-tests, and selection factors were analyzed with logistic regressions. Survival was assessed with Kaplan-Meier curves, log-rank tests, and Cox regressions. Results Of 2577 patients included, Anti-PD1 monotherapy (n=1410) improved survival over cetuximab+chemotherapy (n=577, median survival 14.6 vs. 12.6 months, p=0.015), while anti-PD1+chemotherapy (n=590) showed a nonsignificant trend towards improvement (median survival 14.3 vs. 12.6 months, p=0.053). In HPV-associated disease, survival was equal between regimens. Addition of chemotherapy improved survival over anti-PD1 monotherapy in non-HPV associated tumors with CPS 1-9 (median survival 18.0 vs. 10.3 months, p=0.029) and in oral cavity primaries (median survival 10.3 vs. 7.6 months, p=0.003). Conclusions Subgroups of patients with recurrent or metastatic HNSCC, including non-HPV associated disease with CPS 1-9 and oral cavity primaries, may derive benefits from the addition of chemotherapy to anti-PD1 therapy.
Keywords: cetuximab, Cisplatin Cetuximab, Pembrolizumab Carboplatin Gemcitabine Cisplatin, Fluorouracil, Pembrolizumab Cetuximab, Cisplatin, Fluorouracil Cisplatin, Docetaxel Cetuximab
Received: 15 Feb 2025; Accepted: 31 Mar 2025.
Copyright: © 2025 Lee, Pan, Yaskolko, Chiorazzi, Bhatia, Burtness and Ishizuka. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Daniel Younghoon Lee, Cancer Center, School of Medicine, Yale University, New Haven, 06520-8028, Connecticut, United States
Jeffrey Ishizuka, Cancer Center, School of Medicine, Yale University, New Haven, 06520-8028, Connecticut, United States
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