FDG- and FLT-PET for early measurement of response to 37.5 mg per day of sunitinib in metastatic renal cell carcinoma

Objectives This study evaluated early response to continuous dose of 37.5 mg of sunitinib in metastatic renal cell carcinoma using FDG- and FLT-PET.

Methods FDG- and FLT-PET scans were performed on 20 patients (pts) before and early after 1, 2, 3 or 4 weeks with 37.5 mg continuous daily dose of sunitinib. SUVmax of target lesions and the per-patient average SUVmax were calculated. Prognostic value of FDG- and FLT-PET was evaluated by comparing predictors of baseline average FDG and FLT SUVmax to overall survival. Metabolic and proliferative response was assessed based on the change of average SUVmax relative to baseline (Partial Response ≤ -25% < Stable Disease 25% ≤ Progressive Disease). Logistic regression and the associated likelihood ratio test were used to test for trends in metabolic and proliferative response for different weeks of treatment.

Results Proliferative responses were observed in 9/19 pts and in 2/4 pts at 1 week after the initiation of therapy. Metabolic response was observed in 5/19 pts but 0/4 after 1 week and 1/7 after 2 weeks. There was a significant trend in metabolic response with increasing weeks of treatment (p = 0.045) but no trend with proliferative response (p = 0.93). Baseline FDG-PET tumor average SUVmax correlated inversely with overall survival (p = 0.0036) while baseline FLT-PET imaging did not have prognostic value (p = 0.56).

Conclusions These results show an immediate and sustained proliferative response followed by a delayed metabolic response beginning after two weeks of initiation of therapy in metastatic renal cell carcinoma pts treated with lower-dose continuous daily 37.5 mg sunitinib. FDG-PET was a good prognostic indicator of overall survival while FLT-PET was more sensitive to detecting early pharmacodynamic response.

Research Support This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Pfizer, Inc.