Exploratory analysis of circulating pro- and antiangiogenic factors in metastatic colorectal cancer (mCRC) patients, treated with GONO-FOLFOXIRI plus bevacizumab (BV).

Abstract

e14094 Background: The combination of the anti-VEGF BV with cytotoxic drugs is an efficacious strategy in the treatment of mCRC. It has been hypothesized that the trend over time of circulating levels of pro- and antiangiogenic factors might help to predict treatment's efficacy and to disclose mechanisms of acquired resistance. Methods: Plasma levels of VEGF, placental growth factor (PIGF), soluble VEGF receptor 2 (sVEGFR2) and thrombospondin-1 (TSP-1) were assessed by means of ELISA assay, in a cohort of 25 patients enrolled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF levels were measured on immunodepleted plasma samples collected at baseline (d1), immediately before the second (d15), the fifth (d57) and the twelfth (d155) cycle of therapy and/or at the time of radiographic progression (PD). PIGF, sVEGFR2 and TSP-1 were assessed on plasma samples, collected at the same time points, except for d15. Comparisons were made by the two-sided, nonparametric Wilcoxon paired test. Results: Treatment with GONO-FOLFOXIRI plus BV produced a reduction in plasma VEGF (d15 vs. d1: p = 0.016). VEGF variation was independent of baseline levels (correlation coefficient: 0,105; p = 0.617). VEGF remained lower than at baseline also at d57 (d57 vs. d1; p = 0.002), at d155 (d155 vs. d1; p = 0.001) and at the time of PD (PD vs. day1: p < 0.0001). PIGF levels increased at d57 (d57 vs. d1: p < 0.001) and at d155 (d155 vs. d1: p = 0.019), compared to baseline; a decrease was observed at the time of PD (PD vs. d155: p = 0.049). sVEGFR2 increased at PD, compared to baseline, with a trend towards significance (PD vs. day1: p = 0.083). TSP-1 significantly increased at the time of PD, compared to d155 (PD vs. d155: p = 0.049). Conclusions: Triplet plus BV modulates circulating angiogenic markers, with a relevant effect on VEGF and PIGF levels. The characterization of the angiogenic profile of each patient at any time point might be a new starting point to better individualize antiangiogenic treatment and to focus on innovative therapeutic targets. At present, the small sample size does not allow correlations with clinical outcome. To this end, wider analyses are currently ongoing. No significant financial relationships to disclose.