title: Estimation of renal cell carcinoma treatment effects from disease progression modeling.
abstract: 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; the model incorporated baseline tumor size, a linear disease-progression component, and an exponential drug effect (DE) 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 DE than sorafenib would have 82% power (one-sided α = 0.1) with 50 patients per arm. Model-based quantitation of treatment effect with computed tomography (CT) imaging offers a scaffold on which to develop new, more efficient, phase II trial end points and analytic strategies for RCC.
authors: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA. mmaitlan@medicine.bsd.uchicago.edu
authors: M L
authors: ML
authors: Maitland
authors: K
authors: K
authors: Wu
authors: M R
authors: MR
authors: Sharma
authors: Y
authors: Y
authors: Jin
authors: S P
authors: SP
authors: Kang
authors: W M
authors: WM
authors: Stadler
authors: T G
authors: TG
authors: Karrison
authors: M J
authors: MJ
authors: Ratain
authors: R R
authors: RR
authors: Bies
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data*; D018450:Disease Progression; D007680:Kidney Neoplasms / Q000188:drug therapy*; D015233:Models, Statistical; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib