595 Background: The introduction of regorafenib for the treatment of colorectal cancer represented a sure medical achievement though at a cost of relevant toxicity. As a consequence the lack of predictive factors made the use of regorafenib in the clinical practice challenging. Previous observations suggested that polymorphisms of VEGF and its receptor (VEGFR) genes may regulate angiogenesis and lymphangiogenesis and potentially influence outcome during anti-angiogenesis treatment. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. Methods: From a multicentre experience 138 samples (tumour or blood samples) of colorectal cancer patients receiving regorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients’ progression-free survival (PFS) and overall survival (OS) were analysed. Results: Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS (respectively HR: 0.49, 95% CI: 0.33-0.81, p=0.003 and HR: 0.52, 95% CI: 0.34-0.99, p=0.04). A correlation with disease control rate (DCR) was also observed (DCR 55% vs. 26%, p=0.02). Among clinical factors only ECOG PS was independently correlated with OS (HR: 0.52, 95% CI: 0.21-0.81, p=0.009), whereas no correlation with PFS was evident. Grouping together observations from angiogenesis genotyping and ECOG PS allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. Median OS resulted progressively decreased across these groups (OS not reached, 7.8 and 3.9 months respectively in the favourable, intermediate and unfavourable group, p<0.0001). Conclusions: VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of candidates for regorafenib. This selection opportunity will ultimately improve the therapeutic index of such a treatment approach by limiting treatment to potentially responding patients and sparing unnecessary toxicity to those unlikely to benefit.
Single nucleotide polymorphisms of ABCC5 and ABCG1 transporter genes correlate to irinotecan-associated gastrointestinal toxicity in colorectal cancer patients: A DMET microarray profiling study
