Gene signatures and expression of miRNAs associated with efficacy of panitumumab in a head and neck cancer phase II trial. (July 2018)

• Record Type: Journal Article
• Authors: Siano, Marco; Espeli, Vittoria; Mach, Nicolas; Bossi, Paolo; Licitra, Lisa; Ghielmini, Michele; Frattini, Milo; Canevari, Silvana; De Cecco, Loris
• Is Part Of: Oral oncology. Volume 82(2018)
• Page Start: 144
• Page End: 151
• Publication Date: 2018-07
• Subjects: Head and neck cancer -- Recurrent/metastatic -- Anti-EGFR -- Second line treatment -- Progression-free survival -- Gene expression signatures -- Hypoxia signature -- Microenvironment score -- miRNA; EGFR epidermal growth factor receptor -- mAb monoclonal antibody -- RM recurrent/metastatic -- HNSCC head-neck squamous cell carcinoma -- PFS progression free survival -- ADCC antibody-dependent cellular cytotoxicity -- FFPE formalin-fixed paraffin-embedded -- GEO Gene Expression Omnibus -- ROC Receiver Operating Characteristic -- AUC area under a ROC curve -- ECOG Eastern Cooperative Oncology Group -- WHO World Health Organization -- HR hazard ratio -- CI confidence interval; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2018.05.013
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: Gene signatures gain importance in head and neck cancer as also shown by our group. Cluster3 signature showed predictive potential for anti-EGFR cetuximab treatment. In a prospective trial with panitumumab the Cluster3 predictive value was confirmed. Translation into a clinical assay await validation in wider prospective trials. Abstract: 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.