Objective: Platinum-based chemotherapy plus the anti-EGFR monoclonal antibody (mAb) cetuximab is used to treat recurrent/metastatic (RM) head-neck squamous cell carcinoma (HNSCC). Recently, we defined Cluster3 gene-expression signature as a potential predictor of favorable progression-free survival (PFS) in cetuximab-treated RM-HNSCC patients and predictor of partial metabolic FDG-PET response in an afatinib window-of-opportunity trial. Another anti-EGFR-mAb (panitumumab) was used as the treatment agent in RM-HNSCC patients in the phase II PANI01trial. PANI01 tumor samples were analyzed using functional genomics to explore response predictors to anti-EGFR therapy. Materials and methods: Whole-gene expression and real-time PCR analyses were applied to pre-treatment samples from 25 PANI01 patients. Three gene signatures (Cluster3 score, RAS onco-signature, microenvironment score) and seven selected miRNAs were separately analyzed for association with panitumumab efficacy. Results: Cluster3 expression levels had a profile with a significant bimodal separation of samples (P = 3.08 E−13). Higher RAS activation, microenvironment score, and miRNA expression were associated with low-Cluster3 patients. The same biomarkers were separately associated with PFS. Patients with high-Cluster3 had significantly longer PFS than patients with low-Cluster3 (median PFS: 174 versus 51 days; log-rank P = 0.0021). ROC analysis demonstrated accuracy in predicting PFS (AUC = 0.877). Conclusions: Despite differences in clinical settings and anti-EGFR inhibitors used for treatment, response prediction by the Cluster3 signature and selected miRNAs was essentially the same. Translation into a useful clinical assay requires validation in a broader setting.
Gene signatures and expression of miRNAs associated with efficacy of panitumumab in a head and neck cancer phase II trial / M. Siano, V. Espeli, N. Mach, P. Bossi, L. Licitra, M. Ghielmini, M. Frattini, S. Canevari, L. De Cecco. - In: ORAL ONCOLOGY. - ISSN 1368-8375. - 82(2018 Jul), pp. 144-151.
|Titolo:||Gene signatures and expression of miRNAs associated with efficacy of panitumumab in a head and neck cancer phase II trial|
|Parole Chiave:||anti-EGFR; gene expression signatures; head and neck cancer; hypoxia signature; microenvironment score; mirna; progression-free survival; recurrent/metastatic; second line treatment; oral surgery; oncology; cancer research|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||lug-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.oraloncology.2018.05.013|
|Appare nelle tipologie:||01 - Articolo su periodico|