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The phase III MAX clinical trial randomised patients with metastatic colorectal cancer (mCRC) to receive first-line capecitabine chemotherapy alone or in combination with the anti-VEGF-A antibody bevacizumab (± mitomycin C). We utilised this cohort to examine whether single nucleotide polymorphisms (SNPs) in  VEGF-A ,  VEGFR1 , and  VEGFR2  are predictive of efficacy outcomes with bevacizumab or the development of hypertension. Genomic DNA extracted from archival FFPE tissue for 325 patients (69% of the MAX trial population) was used to genotype 16 candidate SNPs in  VEGF-A ,  VEGFR1 , and  VEGFR2,  which were analysed for associations with efficacy outcomes and hypertension. The  VEGF-A  rs25648 ‘CC’ genotype was prognostic for improved PFS (HR 0.65, 95% CI 0.49 to 0.85;  P  = 0.002) and OS (HR 0.70, 95% CI 0.52 to 0.94;  P  = 0.019). The  VEGF-A  rs699947 ‘AA’ genotype was prognostic for shorter PFS (HR 1.32, 95% CI 1.002 to 1.74;  P  = 0.048). None of the analysed SNPs were predictive of bevacizumab efficacy outcomes.  VEGFR2  rs11133360 ‘TT’ was associated with a lower risk of grade ≥ 3 hypertension ( P  = 0.028). SNPs in  VEGF-A, VEGFR1  and  VEGFR2  did not predict bevacizumab benefit. However,  VEGF-A  rs25648 and rs699947 were identified as novel prognostic biomarkers and  VEGFR2  rs11133360 was associated with less grade ≥ 3 hypertension.

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VEGF-A, VEGFR1 and VEGFR2 single nucleotide polymorphisms and outcomes from the AGITG MAX trial of capecitabine, bevacizumab and mitomycin C in metastatic colorectal cancer