Circulating baseline plasma cytokines and angiogenic factors (CAF) as markers of tumor burden and therapeutic response in a phase III study of pazopanib for metastatic renal cell carcinoma (mRCC).

Abstract

4553 Background: Pazopanib is a multi-kinase inhibitor approved for the treatment of mRCC. Plasma CAF analyses from phase II and III studies previously identified candidates (HGF, IL-6, IL-8, TIMP-1, VEGF, E-Selectin and OPN) that significantly correlated with PFS for patients receiving pazopanib (ASCO 2010, #4522). IL-8, and OPN were also found to be prognostic in patients enrolled in the placebo arm, while IL-6 was both prognostic and predictive (GU,ASCO 2011 #334). Methods: In this study, plasma samples (n=344) from a phase III randomized, placebo-controlled trial were analyzed for CAFs by SearchLight multiplex assays in a CLIA-certified laboratory. Correlations of baseline CAF levels with baseline sum of longest tumor diameter (SLD), maximum tumor shrinkage, and other clinical parameters were completed using the Spearman method. A seven factor angiogenic signature (IL6, IL8, HGF, OPN, TIMP1, VEGF, and E-Selectin) was generated by hierarchical clustering (UPGMA, Euclidean distance). Patients were strat...