Predictive Value of Circulating Endothelial Cell (CEC) Levels in Metastatic or Locally Advanced Neuroendocrine Digestive Tumor Patients Treated With Chemotherapy and Bevacizumab

ABSTRACT Background The efficacy/safety of bevacizumab in combination with chemotherapy was investigated in patients (pts) with advanced progressive digestive neuroendocrine tumors (DigNET) (phase II BETTER study (ML20383)). Circulating endothelial cell levels were explored as potential prognostic or predictive marker. Methods Pts were enrolled in two arms depending on tumor primary localisation. Pts with duodeno-pancreatic NET were treated with 5-FU/streptozocin combined to bevacizumab (arm 1, n = 34). Patients with other digNET received capecitabine combined to bevacizumab (arm 2, n = 49). In 50 dig NET patients, CEC levels were monitored at several time points: -before treatment (baseline, BL), -on day 2 (d2) of cycle 1 (C1), -on day 22 (d22) of cycle 1 (C1) for arm 1 and day 1 (d1) of cycle 2 (C2) for arm 2, -at day 1 of each of the subsequent cycles and at the end of treatment. CECs were measured in 1ml erythocyte lysed whole blood by four color flow cytometry (FCM) and identified by a CD45-CD31+CD1467-amino-actinomycin (7AAD)- phenotype. Relation between CEC levels and clinico-biological characteristics, response to treatment and progression/death at 1 or 2 years (1 yr-, 2 yr-PFS) was examined. Non parametric Wilcoxon tests were used to analyze change from baseline and to evaluate the association beteween CEC values and efficacy parameters. Results Median CEC values were low at BL (4 CEC/mL) and similar for the 2 arms. CEC levels significantly increased on C1d2 onlv (media value: 7CEC/mL for the 2 pooled arms, p = 0.019). A trend towards an association between changes in CEC levels between BL and C1d2, and progression/death during the first two years of treatment was observed (p = 0.078). Conclusions Increased CECs at baseline could be an indicator of shorter PFS in digNET treated with the combination of bevacizumab and chemotherapy. The mechanism of increased CECs at day 2 of treatment remains to be understood. Disclosure E. Mitry: Honoraries: Roche. K. Joly: Employment: Roche. M. Ducreux: Consultant: Roche, Merck Serono Honoraries: Roche, Merck Serono, Amgen, Bayer, Fresenus, Pfizer, Sanofi Clinical research project: Pfizer, Chugai, Merck Serono. E. Baudin: Honoraries : Scientific committee of BETTER Trial. All other authors have declared no conflicts of interest.