PK‐PD modeling of individual lesion FDG‐PET response to predict overall survival in patients with sunitinib‐treated gastrointestinal stromal tumor

Pharmacometric models were developed to characterize the relationships between lesion‐level tumor metabolic activity, as assessed by the maximum standardized uptake value (SUV(max)) obtained on [(18)F]‐fluorodeoxyglucose (FDG) positron emission tomography (PET), tumor size, and overall survival (OS) in 66 patients with gastrointestinal stromal tumor (GIST) treated with intermittent sunitinib. An indirect response model in which sunitinib stimulates tumor loss best described the typically rapid decrease in SUV(max) during on‐treatment periods and the recovery during off‐treatment periods. Substantial interindividual and interlesion variability were identified in SUV(max) baseline and drug sensitivity. A parametric time‐to‐event model identified the relative change in SUV(max) at one week for the lesion with the most pronounced response as a better predictor of OS than tumor size. Based on the proposed modeling framework, early changes in FDG‐PET response may serve as predictor for long‐term outcome in sunitinib‐treated GIST.