Sequential FDG-PET/CT as a Biomarker of Response to Sunitinib in Metastatic Clear Cell Renal Cancer

Purpose: To test the hypothesis that sequential F-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a correlative marker in metastatic clear cell renal cancer (mRCC), patients were treated with sunitinib. Three sequential scans were conducted to determine whether the timing of the investigation was relevant. Experimental Design: Forty-four untreated mRCC patients were enrolled into this prospective phase II study. F-18-FDG-PET/CT scans were conducted before (n = 44) and after 4 weeks (n = 43) and 16 weeks (n = 40) of sunitinib given at standard doses. The primary endpoint was to correlate FDG-PET/CT response (20% reduction in SUVmax) at 4 and 16 weeks with overall survival (OS). Results: Forty-three (98%) patients had FDG-PET/CT avid lesions at diagnosis (median SUVmax = 6.8, range: <2.5-18.4). In multivariate analysis, a high SUVmax and an increased number of PET-positive lesions correlated with shorter OS [HR: 3.30 (95% CI: 1.36-8.45) and 3.67 (95% CI: 1.43-9.39), respectively]. After 4 weeks of sunitinib, a metabolic response occurred in 24 (57%) patients, but this did not correlate with progression-free survival (HR for responders 0.87; 95% CI: 0.40-1.99) or OS (HR for responders 0.80; 95% CI: 0.34-1.85). After 16 weeks of treatment, disease progression on FDG-PET/CT occurred in 28% (n = 12) patients which correlated with a decreased OS and PFS [HR 5.96 (95% CI: 2.43-19.02) and HR 12.13 (95% CI: 3.72-46.45), respectively]. Conclusions: Baseline FDG-PET/CT yields prognostic significant data. FDG-PET/CT responses occur in the majority of patients after 4 weeks of therapy; however, it is not until 16 weeks when the results become prognostically significant. Clin Cancer Res; 17(18); 6021-8. (C) 2011 AACR.