Biomarkers of cetuximab resistance in patients with head and neck squamous cell carcinoma

Olivia Leblanc, Sophie Vacher, Charlotte Lecerf, et al

Abstract


Objective: In patients with head and neck squamous cell carcinoma (HNSCC), cetuximab [a monoclonal antibody targetingepidermal growth factor receptor (EGFR)] has been shown to improve overall survival when combined with radiotherapy in thelocally advanced setting or with chemotherapy in first-line recurrent and/or metastatic (R/M) setting, respectively. While biomarkersof resistance to cetuximab have been identified in metastatic colorectal cancer, no biomarkers of efficacy have been identified inHNSCC. Here, we aimed to identify biomarkers of cetuximab sensitivity/resistance in HNSCC.

Methods: HNSCC patients treated with cetuximab at the Curie Institute, for whom complete clinicopathological data andformalin-fixed paraffin-embedded (FFPE) tumor tissue collected before cetuximab treatment were available, were included.Immunohistochemistry analyses of PTEN and EGFR were performed to assess protein expression levels. PIK3CA and H/N/KRASmutations were analyzed using high-resolution melting (HRM) and Sanger sequencing. We evaluated the predictive value of thesealterations in terms of progression-free survival (PFS).

Results: Hot spot activating PIK3CA and KRAS/HRAS mutations were associated with poor PFS among HNSCC patients treated withcetuximab in the first-line R/M setting, but not among HNSCC patients treated with cetuximab in combination with radiotherapy.Loss of PTEN protein expression had a negative predictive value among HNSCC patients treated with cetuximab and radiotherapy.High EGFR expression did not predict cetuximab sensitivity in our patient population.

Conclusions: Hot spot activating PIK3CA and RAS mutations predicted cetuximab resistance among HNSCC patients in the firstlineR/M setting, whereas loss of PTEN protein expression predicted resistance to cetuximab when combined to radiotherapy.

Cite this article as: Leblanc O, Vacher S, Lecerf C, Jeannot E, Klijanienko J,Berger F, et al. Biomarkers of cetuximab resistance in patients with headand neck squamous cell carcinoma. Cancer Biol Med. 2020; 17: 208-217.doi: 10.20892/j.issn.2095-3941.2019.0153


Keywords


Head and neck squamous cell carcinoma; cetuximab; biomarker; PIK3CA; RAS

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