CENTRAL was a phase II trial of first-line FOLFIRI and bevacizumab in patients with advanced colorectal cancer prospectively stratified according to serum LDH. A pre-planned exploratory analysis (Serum angiogenesis-cENTRAL) was conducted to identify changes in the concentrations of circulating pro-angiogenic factors during treatment as a potential predictive factor for efficacy/resistance.
Patients treated with first-line FOLFIRI + bevacizumab were prospectively assessed for the following circulating pro-angiogenic factors: hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PLGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Assessment was performed before start of treatment and at each cycle until treatment discontinuation. Evaluation was performed by an ELISA-based technique.
73 patients were evaluable for the SENTRAL analysis: in this population mPFS was 12.8 months and mOS was 24.5 months. Among tested circulating factors, FGF-2 levels correlated with clinical outcome in this population. In particular we observed progressive disease in respectively 1/35 (3%) patients showing an increase in FGF-2 levels starting from first cycle to first-radiological evaluation and in 8/38 (21%) patients showing a decrease in FGF-2 levels (p = 0.03). Median PFS for patients showing an increase in FGF-2 levels was 16.6 months vs 8 months for patients showing a decrease in FGF-2 levels (HR:0.65, 95%CI:0.37-1.13, p = 0.12). Improved overall survival for patients showing an increase in FGF-2 levels, compared to patients demonstrating a decrease in FGF-2 levels (24.8 vs 20.7 months, HR:0.43, 95%CI:0.19-0.98, p = 0.04) was also seen.
This preplanned, prospective analysis suggests that early increase (at 8-10 weeks timepoint) in circulating FGF-2 levels could be used as a marker to identify patients who are more likely to gain benefit from first-line FOLFIRI + bevacizumab based therapy.
Clinical trial identification
Trial protocol: Eudract number 2012-005048-46
Legal entity responsible for the study
Gruppo Italiano per lo Studio dei Carcinomi del tratto Digerente (GISCAD)
All authors have declared no conflicts of interest.