CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

Background:

Blood-based biomarkers may be particularly useful for patient selection and prediction of treatment response for angiogenesis inhibitors. Circulating endothelial cells (CECs) and haematopoietic progenitor cells (HPCs) might have a role in tumour angiogenesis and in tumour growth. Measurement of CECs and HPCs in the blood of patients could be a simple, non-invasive way to monitor or predict responses to treatment.

Methods:

(VEGFR2⁺) CECs_, (CD133⁺) HPCs, plasma vascular endothelial growth factor (VEGF) and erythropoietin were measured in blood from 25 non-small cell lung cancer (NSCLC) patients before and during treatment with sorafenib plus erlotinib (SO/ER). In order to assess the drug specificity of changes in CECs and HPCs, 18 patients treated with bevacizumab plus erlotinib (BV/ER) and 10 patients with erlotinib (ER) monotherapy were studied. Response was measured in all patient groups by Response Evaluation Criteria in Solid Tumors (RECIST).

Results:

At day 7, SO/ER-treated patients showed a three-fold increase in CECs (P<0.0001) comparable to BV/ER-treated patients (P<0.01), and the CECs did not change with erlotinib treatment (P=0.8). At day 7, CD133⁺/HPCs decreased with SO/ER treatment (P<0.0001). HPC numbers did not change with either BV/ER or erlotinib. In SO/ER-treated patients pre-treatment CD133⁺/HPCs were significantly lower in responders (P=0.01) and pre-treatment CD133⁺/HPC numbers lower than the median correlated with a longer time-to-progression (TTP) (P=0.037).

Conclusion:

Pre-treatment CD133⁺/HPCs are a promising candidate biomarker to further explore for use in selecting NSCLC patients who might benefit from SO/ER treatment.