Pharmacodynamic (PD) evaluation of soluble proteins from a phase I trial of lapatinib (L) in combination with sorafenib (S).

e21139 Background: At ASCO 2011 we presented safety and efficacy results from a phase I study of L in combination with S in patients with solid tumors refractory to standard therapy (NCT00984425). To investigate potential biomarkers of biological activity of this combination, we analyzed serum levels of a panel of soluble proteins characterizing the oncogenic signalling pathways targeted by L and S (VEGF, sVEGFR-2, EGF, sEGFR, sHER2/neu), and others mediators of angiogenesis such as sPDGFR, IL-8, IL-6, bFGF, PIGF, TGF-α e β, HGF. Methods: Serum samples from 22/30 patients enrolled in this trial were prospectively collected at baseline and then every two months until treatment discontinuation. Serum levels of VEGF, sVEGFR-2, EGF, sEGFR, sHER2/neu and sPDGFR were measured via enzyme-linked immunoadsorbent assays analysis (ELISA). Possible correlations between serum proteins levels and disease-control rate (SCR), PFS or OS were assessed by logistic and Cox regression model, respectively. Results: Analysis of...