Abstract #5432: VEGF(R)-targeted treatment specific increase of circulating endothelial cells in non-small-cell lung cancer patients

For treatment of non-small cell lung cancer (NSCLC) patients the monoclonal antibody bevacizumab (Avastin®) is FDA-approved as part of first line treatment and the multi-targeted tyrosine kinase (TK)-inhibitor sorafenib (Nexavar®) is currently being investigated in various phase II/III trials. Currently, no data are available on circulating endothelial cell (CEC) levels in NSCLC patients treated with anti-angiogenic agents. Here we describe the changes in CEC numbers in NSCLC patients during treatment with either bevacizumab or sorafenib plus the EGFR-inhibitor erlotinib and correlate these changes with clinical outcome parameters. CECs, characterized by CD45^neg/CD34^bright/CD133^neg/VEGFR2^pos_,were assessed in 53 NSCLC patients; 18 treated with bevacizumab (15 mg/kg every 21 days) plus erlotinib (150 mg/day), 25 treated with sorafenib (400 mg twice daily) plus erlotinib and 10 treated with monotherapy erlotinib. Blood was taken before treatment (D1), on D7 and D21. CEC numbers were compared with ¹⁸FDG-PET and H₂¹⁵O-PET (on D1 and D21) and survival. After 7 days of treatment bevacizumab treated patients showed an increase in CECs of 124% (median, from 59 to 132 cells/mL, p=0.002) and sorafenib treated patients an increase of 191% (median, from 44 to 129 cells/mL , p=0.000). CECs during monotherapy erlotinib did not change after 7 days of treatment (median, from 48 to 51 cells/mL, p=0.8). The change in CEC levels after 7 days and 21 days of treatment was not correlated with metabolic tumor response, as assessed by ¹⁸FDG-PET, and changes in tumor blood flow, as assessed by H₂¹⁵O-PET. In bevacizumab treated patients no correlation was found with survival. For the sorafenib treated patients the follow up period is currently too short to allow survival assessment. In conclusion, CECs increased in NSCLC patients treated with bevacizumab or sorafenib in combination with erlotinib, but not with erlotinib monotherapy. This suggests its specificity for anti-VEGF(R) targeted agents, irrespective of the anti-angiogenic mechanism (indirect or direct receptor-mediated) of the treatment. In these trials combining an anti-angiogenic agent with erlotinib in NSCLC, changes in CEC levels alone did not correlate with clinical data. Therefore we suggest that a combination of predictive markers reflecting the activity of both agents should be pursued in the future.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5432.