From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy

• Published in: Cancers 2020-05, Vol.12 (5), p.1330
• Main Authors: Giampieri, Riccardo, Ziranu, Pina, Daniele, Bruno, Zizzi, Antonio, Ferrari, Daris, Lonardi, Sara, Zaniboni, Alberto, Cavanna, Luigi, Rosati, Gerardo, Casagrande, Mariaelena, Pella, Nicoletta, Demurtas, Laura, Zampino, Maria Giulia, Sozzi, Pietro, Pusceddu, Valeria, Germano, Domenico, Lai, Eleonora, Zagonel, Vittorina, Codecà, Carla, Libertini, Michela, Puzzoni, Marco, Labianca, Roberto, Cascinu, Stefano, Scartozzi, Mario
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Angiogenesis; Antiangiogenic agents; Bevacizumab; Biomarkers; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Cytokines; Drug resistance; Enzyme-linked immunosorbent assay; Fibroblast growth factor 2; Folinic acid; Hepatocyte growth factor; Hypoxia; Immunotherapy; Interleukin 8; Irinotecan; Kinases; Metastases; Monoclonal antibodies; Monocytes; Patients; Placenta; Plasma; Response rates; SDF-1 protein; Survival analysis; Targeted cancer therapy; Vascular endothelial growth factor; Vascular endothelial growth factor receptors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12051330

In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), 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). Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio-HR: 0.73, 95% Confidence Interval-CI: 0.43-1.27, = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46-1.33, = 0.35). Our pre-planned, prospective analysis suggests that circulating FGF-2 levels' early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy.