Identification of a gene expression profile associated with progression-free survival (PFS) in relapsed or metastatic (RM) head and neck squamous cell cancer (HNSCC) patients (pts) treated with first-line cetuximab and platinum therapy.

Abstract

6027 Background: First-line chemotherapy with platinum and cetuximab is usually offered to RM-HNSCC pts. In the Extreme trial a median PFS time of 5.6 months was reported. However, a small fraction of pts achieves a prolonged PFS (> than 12 months). Until now, no recognized predictive biological factor has been identified. Methods: A group of 14 pts treated with a first-line platinum and cetuximab with a PFS exceeding 12 months (long PFS) and a group of 26 pts with a PFS less than 5.6 months (short PFS) were selected. Tumor specimens of the recurrence (25 cases) or, if not available, of the primary tumor were collected. In order to identify molecular profiles deregulated between the 2 groups, a gene expression microarray analysis was performed using the Whole-Genome DASL assay and HumanHT-12_v4 BeadArray chips (lllumina). Results: The 2 groups were well balanced in regard to recognized prognostic factors (performance status, weight loss, prior radiotherapy, tumor grade, site of primary tumor, residual disease at primary tumor site). Mean PFS was 21 months in long (range 13-36) and 4 months in short PFS group (range 1-5). By class comparison analysis between the 2 groups, the expression pattern of 136 genes was found differentially expressed (FDR<0.05). In long PFS group, EGFR and genes associated to EGFR pathway including CDCP1 and EPGN were up regulated, as well as its ligand (EREG). Several members of the Kallikrein serine proteases gene family are present among the most upregulated genes in long PFS group, suggesting the involvement of extracellular-matrix remodelling. In addition to cellular morphology, pathways analysis showed an enriched modulation of genes belonging to cell-to-cell signalling, DNA replication/DNA repair and lipid metabolism. Conclusions: Our analysis suggests that a specific molecular signature may be associated with long and short PFS after platinum/cetuximab first line chemotherapy in RM-HNSCC pts. To our knowledge, it is the first study attempting to generate hypotheses in this field and further validation is required.