The association of toxicities and outcomes with circulating endothelial cells (CEC) in non-small cell lung cancer (NSCLC) patients (pts) treated with bevacizumab (Bev).

Abstract

e19012 Background: Bev in combination with chemotherapy (CT) is a standard treatment for pts with stage IV NSCLC. However, there are no established biomarkers to improve benefit-to-risk profile of therapy. CEC are a marker of vascular turnover. We hypothesized CEC may be associated with treatment outcome/toxicity. Methods: Stage IV NSCLC pts were treated with Bev along with CT of choice per clinician. CEC were measured at baseline and after 2 cycles of Bev-containing therapy. CellSearch (Veridex, New Jersey) was used to capture and quantify CEC via immunomagnetic and immunofluorescence techniques. CEC were enumerated as nucleated, CD146+/CD105+/CD45- cells in 4 mL of blood. For comparison, baseline CEC were also collected in 3 other groups; healthy subjects, stage I-III NSCLC, and advanced solid tumor pts. Chi-square tests and non-parametric methods were used to assess associations between CEC and pt/disease characteristics, toxicity, and proportional hazards models were used for comparisons of progression free and overall survival (PFS and OS). Results: Evaluated were 62 individuals: 29 stage IV NSCLC, 10 stage I-III NSCLC, 13 advanced solid tumors (melanoma, sarcoma, renal and adrenal cancers), and 10 healthy subjects. The median of CEC/ml blood in healthy subjects was 6. Based on its distribution, CEC >13/ml was deemed elevated. Elevated CEC was seen in 48% of stage IV NSCLC (median 12/ml), in comparison to 20% of stage I-III NSCLC (8/ml) and 23% of advanced solid tumors (6/ml) Baseline CEC in stage IV NSCLC was independent of patient/ disease characteristics including site of disease and tumor size. CEC increased during treatment in most patients (61%). CEC doubling between baseline and cycle2 was associated with more cytopenia and hemorrhage. (75% vs 20%, p=0.05 and p=0.03 for absolute and relative CEC changes). Baseline CEC and changes during treatment did not correlate with response (p≥ 0.32) and pts with elevated baseline CEC had a trend towards worse PFS (p=0.09) and OS (p=0.10). Conclusions: CEC are commonly elevated in advanced NSCLC. CEC increases may be predictive of adverse events from Bev-CT and when elevated at baseline may suggest worse PFS.