The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma

There is no established biomarker for cetuximab efficacy in recurrent head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to evaluate the prognostic and predictive impact of PTEN, cMET, and p16 expression in recurrent HNSCC. In this retrospective study, 112 patients with recurrent HNSCC received chemotherapy (CT) alone (n=37) or chemotherapy with cetuximab (n=75). PTEN, cMET, and p16 protein expression were evaluated by immunohistochemistry. The median overall survival (mOS) for the patients treated with cetuximab+CT versus CT alone was 11.4 months and 7.0 months, (p=0.949). The median progression-free survival (mPFS) was 6.2 months versus 3.0 months (p=0.154). Patients with PTEN loss exhibited a mOS of 5.8 months versus 10.5 months (p=0.002) and a mPFS of 3.2 months versus 4.7 months (p=0.019). A multivariate analysis identified an independent association between PTEN loss and OS (HR 2.27; 95% confidence 95% CI 1.27-4.08; p=0.006) and with PFS (HR 1.85; 95% CI 1.09-2.99; p=0.022). A negative prognostic impact of PTEN loss was observed in the patients treated with cetuximab+CT, and not in the CT only group. Expression of cMET and p16 showed no impact on OS or PFS. The present findings confirm that PTEN is a prognostic factor for metastatic HNSCC and they support further studies of PTEN expression to evaluate its predictive value to cetuximab response.