Circulating pro-angiogenic markers in patients receiving first-line FOLFIRI + bevacizumab. The SENTRAL (Serum angiogenesis-cENTRAL) pre-planned analysis of the Italian Research Group for Digestive Tract Cancer (GISCAD) CENTRAL trial (ColorEctalvastiNTRiAlLdh)

Date

08 Oct 2016

Session

Poster Display

Presenters

mario Scartozzi

Citation

Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370

Authors

M. Scartozzi1, R. Giampieri2, B. Daniele3, D. Ferrari4, S. Lonardi5, A. Zaniboni6, L. Cavanna7, G. Rosati8, N. Pella9, M.G. Zampino10, P. Sozzi11, L. Casula1, S. Rota12, D. Germano3, M. Puzzoni1, C. Loretelli2, V. Zagonel5, R. Labianca13, L. Frontini12, S. Cascinu14

Author affiliations

  • 1 Medical Oncology, University of Cagliari, 09042 - Cagliari/IT
  • 2 Oncology, Università Politecnica delle Marche, Dipartimento Scienze Cliniche e Molecolari - Azienda Ospedaliera Ospedali Riuniti di Ancona, 60126 - Ancona/IT
  • 3 Oncology, Azienda Ospedaliera G. Rummo, 82100 - Benevento/IT
  • 4 Oncologia - Ss Cure Palliative, Ospedale San Paolo, Milano/IT
  • 5 Department Of Oncology, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 6 Oncology, Fondazione Poliambulanza, Brescia/IT
  • 7 Oncology, Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto, Piacenza/IT
  • 8 Oncologia Medica, Azienda ospedaliera Regionale S. Carlo di Potenza, Potenza/IT
  • 9 Oncologia, Azienda Ospedaliera Universitaria-Udine Sta Maria della Misericordia, Udine/IT
  • 10 Oncologia, Istituto Europeo di Oncologia, 20141 - Milano/IT
  • 11 Medical Oncology, Ospedale degli Infermi, 13900 - Biella/IT
  • 12 Coordinamento Studi Clinici, Fondazione GISCAD, Milano/IT
  • 13 Director, Cancer Center, Azienda Ospedaliera Papa Giovanni XXIII, 24127 - Bergamo/IT
  • 14 Medical Oncology, Azienda Ospedaliero - Universitaria Policlinico di Modena, 47121 - Modena/IT
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Background

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.

Methods

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.

Results

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.

Conclusions

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)

Funding

GISCAD

Disclosure

All authors have declared no conflicts of interest.

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