Circulating endothelial cell (CEC) monitoring in metastatic colorectal cancer (mCRC) patients (pts) treated with first-line bevacizumab (BEV)-based combination regimens: Results of the randomized phase II FNCLCC-ACCORD 13/0503 trial

Abstract

4071 Background: There is no validated biomarker to predict the efficacy of BEV, an anti-VEGF monoclonal antibody. Rare cell subpopulations such as CEC are good candidates. Methods: Pts with mCRC, aged 18–75 yrs, ECOG performance status (PS) 0–2, and no prior palliative chemotherapy were randomized to either BEV (5 mg/kg) + FOLFIRI every 2 weeks (arm A, 12 cycles) or BEV (7,5 mg/kg) + XELIRI every 3 weeks (arm B, 8 cycles). BEV was continued until disease progression [PD]. The primary endpoint was crude 6-month progression-free survival (PFS) rate. In consenting pts, CEC (CD45-CD31+CD146+7- amino-actinomycin- cells) were measured at baseline (Day [D]1, before treatment), D8, and at the end of cycle 1 (D15 or 22) in 1-mL whole blood by four-color flow cytometry according to a method we established previously (J Immunol Methods 2008). Results were correlated to pts’ characteristics and primary endpoint (Wilcoxon's, Fisher's, and trend tests). Results: From 03/06 to 01/08, we enrolled 145 pts (male, 56%; median age, 61 yrs; PS 0–1, 91%; number of metastatic sites [1/2/>2], 45/48/8%). Pts with at least one CEC measurement (n=99; arm A, 51; arm B, 48) did not differ from the 46 other pts regarding sex, age, PS, and number of metastatic sites. Baseline CEC levels (n=97; median, 16/mL) were higher in PS 1–2 pts (n=42) than in PS 0 pts (n=55) (17 vs. 12/mL, p=0.02) (age, sex, number of metastatic sites: NS) and in pts with PD (n=17) than in pts with non- PD (n=80) at 6 months (30 vs. 15/mL, p=0.004). CEC levels were higher at the end of cycle 1 in the PD group (n=17) than in the non-PD group (n=74) (34 vs. 14/mL, p=0.01). The 6-month PFS rate varied from 0% to 32% in the 4 groups defined by baseline and end-of-cycle- 1 CEC values (cutoff: baseline median) (trend test, p=0.006) ( table ). Conclusions: Baseline and end-of-cycle-1 CEC levels may predict tumor control in patients with mCRC starting first-line BEV + chemotherapy. [Table: see text] [Table: see text]