Randomized phase II study of preoperative afatinib in untreated head and neck cancers: predictive and pharmacodynamic biomarkers of activity.

Journal

Scientific reports

ISSN: 2045-2322

Titre abrégé: Sci Rep

Pays: England

ID NLM: 101563288

Informations de publication

Date de publication:
18 Dec 2023

Historique:

received: 12 07 2023

accepted: 13 12 2023

medline: 19 12 2023

pubmed: 19 12 2023

entrez: 19 12 2023

Statut: epublish

Résumé

There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21-28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P < 0.001; FDR = 0.01). Although exploratory, phosphoproteomics-based biomarkers deserve further investigations as predictors of afatinib efficacy.

Identifiants

DOI: 10.1038/s41598-023-49887-4 PMID: 38110561

pubmed: 38110561

doi: 10.1038/s41598-023-49887-4

pii: 10.1038/s41598-023-49887-4

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

22524

Informations de copyright

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