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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

1791 - Predictive significance of tumour angiogenic and anti-angiogenic VEGF-A splice variants in patients with metastatic colorectal cancer

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

George Pentheroudakis

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

G. Pentheroudakis1, V. Kotoula2, G. Koliou1, K. Papadopoulou1, E. Samantas1, T. Makatsoris1, V. Karavasilis1, D. Mauri1, I. Efstratiou1, D. Bafaloukos1, P. Papakostas1, A. Psyrri1, G. Papatsibas1, G. Zarkavelis1, A. Goussia1, I. Bompolaki1, G. Oikonomopoulos1, A.N. Christopoulou1, D.G. Pectasides1, G. Fountzilas1

Author affiliations

  • 1 Data Office, Hellenic Cooperative Oncology Group (HeCOG), 11524 - Athens/GR
  • 2 Data Office, Hellenic Cooperative Oncology Group (HeCOG), Athens/GR
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Abstract 1791

Background

Alternate (distal) splicing of VEGF-A isoforms results in production of VEGF-Axxxb anti-angiogenic proteins that fail to activate the angiogenic cascade. Bevacizumab, widely used in patients with metastatic colorectal cancer (mCRC), binds both VEGFA and VEGFAxxxb isoforms.

Methods

Formalin-fixed paraffin-embedded primary tumours from mCRC patients treated in 1st line with FOLFIRI+Bevacizumab (Nbev=285) or FOLFIRI only (Nchem=75) were collected, mRNA was extracted, amplified and quantified with qRT-PCR (Taqman-MGB-assays) for the relative expression of VEGF-A 121a, 121b, 145a, 145b, 165a, 165b mRNA transcripts.

Results

At a median follow-up of 101.5 months, patients with left-sided (L-CRC) compared to those with right-sided primaries (R-CRC) had longer overall survival (OS) [median OS: 29.2 vs. 18.2 months, p = 0.015]. High VEGFA 145b mRNA expression was an unfavourable factor for PFS (HR = 1.66,95% CI 1.13-2.44, p = 0.009) in Nbev patients, with no prognostic significance in Nchem patients (HR = 0.70, 95% CI 0.34-1.44, p = 0.33). The adverse PFS prognostic effect of 145b was more pronounced in R-CRC patients (HR = 2.62, 95% CI 1.35-5.12, p = 0.005), especially when bevacizumab-treated (HR = 2.85, 95% CI 1.31-6.21, p = 0.008). High VEGFA 121b was adversely prognostic for PFS (HR = 2.48, 95% CI 1.23-5.04, p = 0.012) , OS (HR = 2.00, 95% CI 1.08-3.72, p = 0.028) in right, but not left colon, while high 165b was a favourable prognosticator in left sided disease ( PFS HR = 0.76, 95% CI 0.59-0.99, p = 0.044, OS HR 0.68, 95% CI 0.52-0.90, p = 0.006). At multivariate analysis, right-sided primary was associated with inferior PFS (HR = 1.28, 95% CI 1.00-1.64, p = 0.051) and OS (HR = 1.33, 95% CI 1.02-1.73, p = 0.037), while high 145b mRNA expression consistently retained predictive significance for lack of PFS benefit from bevacizumab therapy (HR = 1.71, 95% CI 1.16-2.53, p = 0.007).

Conclusions

In a cohort of mCRC patients treated with bevacizumab, RQ of VEGF-A 145b mRNA, an anti-angiogenic isoform, may predict for resistance to bevacizumab, without prognostic utility in patients not exposed to the antibody. Differences in biological relevance of various VEGF-A isoforms were shown for right versus left-sided primaries.

Clinical trial identification

Legal entity responsible for the study

Hellenic Cooperative Oncology Group (HeCOG).

Funding

Roche Hellas.

Editorial Acknowledgement

NA

Disclosure

E. Samantas, G. Fountzilas: Advisory board: Roche. T. Makatsoris: Honoraria, advisory role: Roche. P. Papakostas: Advisory role: Roche. A. Psyrri: Consultation, honoraria: Roche. All other authors have declared no conflicts of interest.

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