Estimation of renal cell carcinoma treatment effects from disease progression modeling

To improve future drug development efficiency in renal cell carcinoma (RCC), a disease progression model was developed with longitudinal tumor size data from a phase III trial of sorafenib in RCC. The best fit model was externally evaluated on 145 placebo-treated patients in a phase III trial of pazopanib, and incorporated baseline tumor size, a linear disease progression component, and an exponential drug effect parameter. With the model-estimated effect of sorafenib on RCC growth we calculated the power of randomized phase II trials between sorafenib and hypothetical comparators over a range of effects. A hypothetical comparator with 80% greater drug effect than sorafenib would have 82% power (one-sided α = 0.1) with 50 patients per arm. Model-based quantitation of treatment effect with CT imaging offers a scaffold on which to develop new, more efficient, phase II trial endpoints and analytic strategies for RCC.