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

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. (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. 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. Everolimus decreases (89)Zr-bevacizumab tumor uptake. Further studies are warranted to evaluate predictive value of (89)Zr-bevacizumab PET for everolimus antitumor efficacy.