Prospective assessment of circulating endothelial cells (CECs) as early markers of clear cell renal cell carcinoma (CCRCC) progression in first-line setting: The Circles study (SOGUG 2011-01).

436 Background: Angiogenesis inhibitors have become a cornerstone in the management of clear cell renal cell carcinoma (CCRCC). Since circulating endothelial cells (CECs) counts have been proposed as surrogate biomarkers of angiogenesis, they could potentially be used to assess the activity of such drugs. Methods: An observational prospective study is being performed in 11 institutions members of the SOGUG group. Patients with confirmed CCRCC on first-line treatment who have not progressed after 3 months of therapy are considered eligible. CECs (CD 105+,CD 45-, DAPI + cells assessed by the Cell Search system), are determined every 6 weeks for 15 months or radiological tumor progression. Results: Up to 64 of the 75 scheduled patients have already been recruited. Mean age was 64 years, 73% were men and 27% women. Distribution upon MSKCC risk cathegories was: good 30%, intermediate 58%, poor 3% and not available (N/A) 9%. 57 (90%) patients received sunitinib, 3 (5%) pazopanib, 1 (2%) temsirolimus and was N/A in 3 (5%). The CECs counts were determined in 60 patients. At baseline median was 47 cells/4 ml (range 4-480). When comparing patients who experienced tumor progression while on study (11 cases) with patients who did not (28 CECs/4 ml vs. 73 CECs/4ml respectively), a significant difference was found (p = 0.002, t-student). Several exploratory analysis regarding concomitant conditions and patients and tumor characteristics showed that cases with heavily treated hypertension (8 in 60 patients) had lower baseline CECs counts, though without statistical significance (p = 0.068, t-student). Conclusions: Our data point to a different behaviour of CECs counts among CCRCC patients tretated with anitangiogenic drugs that could lead to identify specific subpopulations. Mature results will be presented at the meeting.