Predictive Biomarkers and Personalized Medicine Analyzing thePivotal Trial ThatComparedSunitiniband IFNa in Renal Cell Carcinoma , Using a Method That Assesses Tumor Regression and Growth

Purpose:We applied a method that analyzes tumor response, quantifying the rates of tumor growth (g) and regression (d), using tumor measurements obtained while patients receive therapy. We used data from the phase III trial comparing sunitinib and IFN-a in metastatic renal cell carcinoma (mRCC) patients. Methods: The analysis used an equation that extracts d and g. Results: For sunitinib, overall survival (OS) was strongly correlated with log g (Rsq1⁄4 0.44, P < 0.0001); much less with log d (Rsq1⁄4 0.04; P1⁄4 0.0002). Themedian g of tumors in these patients (0.00082 per days; log g1⁄4 3.09)was about half that (P <0.001) of tumors in patients receiving IFN-a (0.0015 per day; log g1⁄4 2.81). With IFN-a, the OS/log g correlation (Rsq 1⁄4 0.14) was weaker. Values of g from measurements obtained by study investigators or central reviewwere highly correlated (Rsq1⁄4 0.80).No advantage resulted in including data fromcentral review in regressions. Furthermore,g canbe estimated accurately fourmonths before treatment discontinuation. Extrapolating g in a model that incorporates survival generates the hypothesis that g increased after discontinuation of sunitinib but did not accelerate. Conclusions: In patients with mRCC, sunitinib reduced tumor growth rate, g, more than did IFN-a. Correlating gwith OS confirms earlier analyses suggesting gmay be an important clinical trial endpoint, to be explored prospectively and in individual patients. Clin Cancer Res; 18(8); 2374–81. 2012 AACR.