Abstract

e14512 Background: Bevacizumab (B) + chemotherapy (CT) is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). However, molecular predictors of B efficacy have still not been identified. In this study we verified the role of specific VEGF polymorphisms as predictive markers of the efficacy of B in mCRC patients. Methods: One hundred and forty-nine patients enrolled onto the phase III prospective multicentric randomized “Italian Trial in Advanced Colorectal Cancer (ITACa)” trial were considered for this study. Seventy-four patients received FOLFIRI or FOLFOX plus B and 75 patients received only CT. A peripheral blood sample was collected from each patients and submitted to genomic DNA extraction. Five single nucleotide polymorphisms (SNPs) were analyzed by direct sequencing: VEGF -2578 C/A, -1498 C/T, -1154 G/A, -634 G/C, +936 C/T. All candidate genotypes were evaluated for a potential correlation with objective response rate (ORR) (Chi-square test). Results: In the B-treated group, the presence of VEGF -2578 AA, -634 GG or -1498 CC polymorphisms was associated with a better ORR compared to the other genotypes. In particular, of the 17 patients carrying the VEGF -2578 AA genotype, 14 (82.4%) showed a response, whereas only 30 (54.6%) of the 55 patients carrying -2578 CC or CA responded to therapy (p=0.05). Similarly, of 30 patients with VEGF -634 GG, 23 (76.7%) responded to therapy, whereas only 21 (50%) of the 42 patients with VEGF -634 GC or CC were responders (p=0.03). Moreover, 13 (81.3%) of the 16 patients carrying VEGF -1498 CC were responders, whereas of the 56 patients with VEGF -1498 CT or TT, only 31 (55.4%) showed a response (p=0.07). No differences in terms of ORR were observed in patients receiving only chemotherapy. However, as a result of the low power of the interaction test, the relation between ORR and treatment was very close to statistical significance for VEGF -2578 only (p=0.07). Conclusions: VEGF -2578 C/A seems to be a potential predictive marker for B-based CT in mCRC patients. Further studies on larger case series are now needed to confirm this finding.

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