Dynamic Changes in Plasma Osteopontin as a Markers of Tumor Response in Metastatic Renal Cell Carcinoma (RCC) Patients Treated with Pazopanib

Background In a Phase II RCC study of pazopanib (VEG102616) a response rate of 34.7% and disease control rate (CR + PR +SD) of 80% were observed (Hutson, JCO 2009. Previously, we reported that elevated levels of E-Selectin, lower levels of IL-6 and HGF were correlated with longer PFS and decrease in tumor shrinkage. Higher levels of IL-6 and IL-8 correlated with greater tumor burden (Tran ASCO 2010). IL-8, OPN, HGF and TIMP1 correlated with PFS and IL-6, IL-8 and OPN were prognostic markers (Yuan GU ASCO 2011, Tran ESMO 2011). In this study, we measured CAF levels at baseline, week 4 and week 12 after inititation of pazopanib therapy and evaluated for dynamic changes in CAF as potential marker for tumor response and clinical benefits Methods Six candidate CAFs (TIMP1, IL-6, IL-8, HGF, E-Selectin, and OPN) were measured in 173 patients (pts) whose plasma samples were collected during the treatment at week 4, and week 12 by using Searchlight Protein Array (Aushon). CAF levels at each time point and changes of CAF levels from baseline at week 4 and week 12 were correlated with maximum tumor shrinkage (MTS) by linear regression; PFS by Cox regression; baseline tumor burden using baseline sum of longest tumor diameter and best response by Spearman. Results Decreases in OPN levels from baseline at week 4 (p = 0.030) and week 12 (p = 0.006) show significant correlations with MTS. At week 4, changes in E-Selectin from baseline was trending (p = 0.053) in correlation with MTS. With PFS, changes in IL-6 level from baseline at week 12 has near significant correlation with PFS (p = 0.05). E-Selectin has an inverse baseline to week 4 significant correlation with best response status week 4 (p = 0.0245) but not at week 12. Conclusion Decreasing levels of osteopontin from baseline at week 4 and 12 correlated with improved tumor shrinkage; while increase in IL-6 portends shorter PFS and E-Selectin was inversely correlated with best response status. Additional investigation is needed to evaluate the dynamic changes of CAFs as an approach to monitor patients while on pazopanib therapy as marker of tumor response. Disclosure Y. Liu: Stock ownership: Yes; GSK Membership on an advisory board or board of directors: No Corporate-sponsored research: No Other substantive relationships: No A. Martin: Stock ownership: Yes; GSK Membership on an advisory board or board of directors: No Corporate-sponsored research: No Other substantive relationships: No K.L. Baker-Neblett: Stock ownership: Yes; GSK Membership on an advisory board or board of directors: No Corporate-sponsored research: No Other substantive relationships: No. L.N. Pandite: Stock ownership: Yes; GSK Membership on an advisory board or board of directors: No Corporate-sponsored research: No Other substantive relationships: No. J.V. Heymach: Stock ownership: No Membership on an advisory board or board of directors: Yes; GSK Corporate-sponsored research: Yes; GSK for biomarker analysis. Other substantive relationships: No. All other authors have declared no conflicts of interest.