Abstract 372: Circulating endothelial progenitor cell levels predict survival benefit in metastatic renal cell cancer patients treated with antiangiogenic agents

Abstract

Abstract Background: There is no validated biomarker to predict the efficacy of antiangiogenic therapy in patients with metastatic renal cell carcinoma (MRCC). We tested the hypothesis that circulating endothelial cells (CEC) and circulating endothelial progenitor cell (CEP) could predict clinical outcome in MRCC patients undergoing treatment with tyrosine kinase inhibitors (TKI). Methods: Fifty five patients (pts) with MRCC were monitored both at baseline and day 14 after anti-angiogenic treatment (46 pts received sunitinib and 9, sorafenib). CECs were measured in 1ml erythocyte lysed whole blood by four color flow cytometry (FCM) and identified by a CD45−CD31+CD1467-amino-actinomycin (7AAD)− phenotype. CEPs were measured in 10ml blood after progenitor cell enrichment and were identified by FCM as extremely rare events with a CD45dimCD34+VEGFR2+7AAD− phenotype. Relation between CEC and CEP levels and both response to TKI determined by RECIST criteria after 2 cycles with the Wilcoxon-Mann Whitney test, and progression free survival (PFS) and overall survival (OS) with the Cox model (Log-rank test). Results: CEC and CEP levels at both baseline and day 14 were not correlated to response to TKI. No correlation was found between baseline or day 14 CEC values and PFS or OS. However, pre-treatment CEP levels were correlated to PFS (p=0.01) and OS (p=0.01). Patients with elevated pre-treatment levels of CEP (> 2% of circulating CD34+ cells) had an increased risk of tumor progression and poor prognosis. Changes in CEP levels between day 1 and day 14 were also correlated with PFS (p=0.03). Conclusion: Our results indicate that pre-treatment CEP levels could accurately predict survival in MRCC patients treated with TKI. If these data are confirmed, measurement of CEP levels before TKI therapy in MRCC patients will allow to identify patients who will benefit most from treatment and those who will need to be rapidly switched to another treatment. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 372.