D46 - Selection with a molecUlar PanEl foR Panitumumab EfficAcy in K-ras and n-ras wild type metastatic colorectal cancer (SUPER- PEAK)

Abstract

Background: Currently we are able to exclude from anti-epidermal growth factor receptor (EGFR) treatment patients with putative refractory colorectal tumours (i.e. those harboring a RAS mutant status). However on the other hand a nonnegligible proportion of patients don't fully benefit from the use of chemotherapy in combination with anti-EGFR treatment (cetuximab or panitumumab), although in the absence of a mutation of the RAS genes. Published research data suggested that EGFR gene copy number, PIK3CA mutations, PTEN mutations or copy number variations and BRAF mutations may all represent predictive determinants for anti-EGFR therapy. However these factors were not incorporated into clinical practice particularly because prospective validation is lacking. Trial Design: The SUPER-PEAK is an ongoing, multicentre, biologically enriched, double blinded, prospectively stratified observational study. Patients receiving oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) plus panitumumab as per indication, are divided into 2 prognostic groups on the basis of their molecular profile: favourable and unfavourable (respectively high and low probability for improved RR). According to PIK3CA mutational status, BRAF mutational status and EGFR gene copy number (GCN), patients are prospectively allocated to either the favourable group (PIK3CA and BRAF wild type and EGFR GCN = 2.6) or the unfavourable group (PIK3CA mutation or BRAF mutation or EGFR GCN < 2.6). The study objective is to define a molecular panel able to identify patients more likely to benefit from the use of first-line panitumumab in combination with FOLFOX in terms of response rate (RR) as primary endpoint. Secondary endpoints include early tumour shrinkage (ETS), depth of response (DoR), median progression free-survival (PFS) and median overall survival (OS). To detect a difference in terms of RR among patients with an unfavourable profile and patients with a favourable profile assuming a probability alpha of 0.05 and beta of 0.10, the required sample size is 90 patients. (EudraCTnumber: 2015-001408-72)