Prospective Biomarker Validation Trial Evaluating The Prognostic Role Of The Combined Expression Of Phospho-Insulin Growth Factor Receptor-1 And Matrilysin In Kras (Exon 2) Wild-Type (Wt) Metastatic Colorectal Cancer (Mcrc) Patients Treated With Folfox-6 Plus Panitumumab As First-Line Therapy [Pulse Trial (Gemcad 09-03)].

583 Background: Matrilysin can activate phospho-insulin growth factor receptor-1 (pIGF-1R) through IGFBP-3 degradation, releasing IGF-1. Matrilysin per se has shown poor prognosis in mCRC and the co-expression of matrilysin and pIGF-1R (double positivity, DP) correlates with poor prognosis in WT KRAS refractory patients (pts) treated with anti-EGFR in retrospective analyses. We performed a prospective clinical trial in WT KRAS (exon 2) pts, treated with FOLFOX plus panitumumab in first-line therapy to validate those findings. Methods: Positive cases were defined by immunohistochemistry as those with moderate or strong intensity (++/+++) and u003e 70% expression for both matrilysin and p-IGF-1R (antibody anti-pY1316). The primary end-point was progression-free survival (PFS). Seventy-eight pts and 56 events were required to have an 80% power to detect a difference in median PFS of 6 months (two-sided pu003c 0.05). Results: We screened 196 mCRC pts in 24 centers between Nov/2010 and Apr/2013 and 78 pts met inclusio...