Abstract
Abstract Background: A biomarker allowing to predict the efficacy of targeted therapies would be of great clinical value in patients with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell levels are associated with clinical outcome in mRCC patients undergoing targeted treatments. Methods: The TORAVA trial was a randomized phase II study aimed to determine the efficacy and safety of temsirolimus and bevacizumab combination (arm A) in comparison to 2 control arms, sunitinib (arm B) or bevacizumab and α-interferon (arm C). Samples were collected at baseline and day 14 for each treatment arm. CEC levels were analysed in 117 patients (pts) using the CellSearch™ (Veridex, Warren, NJ) platform. Bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell levels were measured in 10ml blood samples of 42 pts by four-color flow cytometry after progenitor cell enrichment. Relation between CEC and CD45dimCD34+VEGFR2+ progenitor cell levels and clinico-biological characteristics, response to treatment (determined by RECIST criteria after 2 cycles) and progression free survival (PFS) was examined. Results: CEC levels were significantly higher in patients without nephrectomy (p<0.001). A trend between the association of high CEC levels and a PS of 2 was observed (p=0.08). CEC and CD45dimCD34+VEGFR2+ progenitor cell levels at both baseline and day 14 were not correlated to response to treatment. No correlation was found between baseline or day 14 CEC values and PFS. However, pre-treatment CD45dimCD34+VEGFR2+ progenitor cell levels were significantly correlated to PFS (p=0.003). Patients with elevated pre-treatment levels of CD45dimCD34+VEGFR2+ progenitor cell had an increased risk of tumor progression. Conclusion: Our results indicate that pre-treatment CD45dimCD34+VEGFR2+ progenitor cell levels could accurately predict PFS in MRCC patients receiving targeted therapies. The association between CEC and CD45dimCD34+VEGFR2+ progenitor cell levels and overall survival will be presented. These data suggested that measurement of CD45dimCD34+VEGFR2+ progenitor cell levels before targeted therapy in mRCC patients will allow to identify at an early stage patients who will benefit most from treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4127. doi:10.1158/1538-7445.AM2011-4127
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