89Zr-bevacizumab PET : Potential Early Read Out for Efficacy of Everolimus in Metastatic Renal Cell Carcinoma Patients

RATIONALE: Currently, biomarkers that predict efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans in mRCC patients with (89)Zr-bevacizumab, a VEGF-A-binding antibody tracer. Aims were to determine change in tumor tracer uptake after start of everolimus and to explore if (89)Zr-bevacizumab PET can identify patients with early disease progression. METHODS: (89)Zr-bevacizumab PET was done before and 2 and 6 weeks after start of everolimus 10 mg/day in mRCC patients. Routine CT scans were performed at baseline and every 3 months thereafter. Tumor tracer uptake was quantified using maximum Standardized Uptake Value (SUVmax). Endpoints were change in tumor tracer uptake and treatment response on CT after 3 months. RESULTS: Thirteen patients participated. Median SUVmax of 94 tumor lesions was 7.3 (range 1.6-59.5). Between patients, median tumor SUVmax varied up to 8-fold. After 2 weeks, median SUVmax was 6.3 (1.7-62.3) corresponding to a mean decrease of 9.1% (P < 0.0001). Three patients discontinued everolimus early. At 6 weeks, a mean decrease in SUVmax of 23.4% compared to baseline was found in 70 evaluable lesions of 10 patients, with a median SUVmax of 5.4 (1.1-49.4, P < 0.0001). All 10 patients who continued treatment had stable disease at 3 months. CONCLUSION: Everolimus decreases (89)Zr-bevacizumab tumor uptake. Further studies are warranted to evaluate predictive value of (89)Zr-bevacizumab PET for everolimus antitumor efficacy.