ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Mutational Landscape of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Association with Immune Checkpoint Inhibitor Outcomes.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 5 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II, Multi-Center, Single-Arm, Global Study of MEDI4736 Monotherapy in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
A Phase II, Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy, Tremelimumab Monotherapy, and MEDI4736 in Combination With Tremelimumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy and MEDI4736 in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Who cites it
5 citing papers in PubMed.
- Fundamentals and emerging frontiers in p53-targeted drug development.Biochemistry and biophysics reports · 2026Review
- Genomic Enrichment and Functional Impact of TP53 and CYLD Alterations in Recurrent and Metastatic HPV-Associated Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Unraveling the molecular landscape: an overview on gene expression, epigenetic alterations, and therapeutic challenges in head and neck squamous cell carcinoma.Molecular genetics and genomics : MGG · 2026Review
- The ALP score: a novel composite index for prognostic risk stratification to chemo-immunotherapy in advanced non-small cell lung cancer.Frontiers in immunology · 2026Article
- Salivary and Serum Liquid Biopsy Biomarkers for HPV-Associated Oral and Oropharyngeal Cancer: A Narrative Review.Journal of clinical medicine · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeUnderstanding the mutational landscape of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is important in identifying biomarkers to determine which patients may benefit from immune checkpoint inhibitors (ICI). EXPERIMENTAL
designThe HAWK (NCT02207530), CONDOR (NCT02319044), and EAGLE (NCT02369874) studies evaluated R/M HNSCC treatment with durvalumab or durvalumab-tremelimumab. Tumor tissue samples pooled from HAWK/CONDOR (n = 153) and plasma cell-free DNA samples from EAGLE (n = 285) were analyzed to identify somatic alterations and association with survival.
resultsThe mutational landscape was similar in tissue and plasma. Compared with the wild type, TP53 mutations were associated with significantly shorter overall survival (OS; HR; 95% confidence interval) with standard of care (SoC; EAGLE: 2.12; 1.20-3.78) and ICIs (HAWK/CONDOR: 1.49; 1.05-2.12 and EAGLE: 1.44; 0.99-2.10). In EAGLE, patients with TP53 mutations had significantly longer OS with durvalumab-tremelimumab versus SoC (P = 0.045). KMT2D mutations were associated with a trend toward longer OS (HR; 95% confidence interval) versus the wild type in HAWK/CONDOR (0.81; 0.56-1.19) and a trend toward longer OS with ICIs versus SoC in EAGLE. For both mutations, a European Cooperative Oncology Group performance status of 1 was associated with worsened OS, and PD-L1 positivity was associated with improved OS.
conclusionsThis is the first large-scale study to show the mutational landscape of R/M HNSCC and its association with clinical outcomes in patients treated with ICIs or SoC. The TP53 mutation was a negative prognostic marker; however, treatment with durvalumab-tremelimumab significantly improved survival over SoC. Further investigation of KMT2D as a predictive biomarker for immunotherapy in R/M HNSCC is warranted.
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