BACKGROUND: Aflibercept (ziv-aflibercept) is an anti-angiogenic agent recently approved in combination with FOLFIRI for the treatment of metastatic @entity14 (mCRC) @entity1 previously treated with @entity901 . Despite heterogeneity in response to aflibercept, no biomarkers for efficacy or adverse effects have been identified. Here we present biomarker data from the randomised phase II AFFIRM trial assessing aflibercept in combination with mFOLFOX6 first line in mCRC. METHODS: Ninety-six somatic mutations in key oncogenic drivers of mCRC and 133 common single-nucleotide polymorphisms (SNPs) in @entity7 ( @entity7 ) pathway genes were analysed, and 27 plasma markers measured at baseline, during and after treatment. We assessed correlations of these three classes of biomarkers with progression-free survival (PFS) and adverse events (AEs). RESULTS: Somatic mutations identified in @entity984 , @entity817 , @entity8497 , @entity10160 and @entity10241 did not significantly correlate with PFS (multiple testing-adjusted false discovery rate (FDR) or multiple testing-adjusted FDR>0.3). None of the individual SNPs correlated with PFS (multiple testing-adjusted FDR>0.22), but at the gene level variability in @entity23877 significantly correlated with PFS (multiple testing-adjusted FDR=0.0423). Although none of the plasma markers measured at baseline significantly correlated with PFS, high levels of circulating @entity687 at baseline together with increased levels of @entity687 during treatment were significantly associated with reduced PFS (multiple testing-adjusted FDR=0.0478). No association was found between biomarkers and AEs. CONCLUSIONS: This represents the first biomarker study in mCRC treated with aflibercept. High @entity687 plasma levels at baseline and subsequent increases in @entity687 were associated with worse PFS, suggesting that @entity687 may act as a potentially predictive biomarker of aflibercept treatment outcome.British Journal of Cancer advance online publication, 10 September 2015; doi:10.1038/bjc.2015.329 www.bjcancer.com.

Evaluation of efficacy and safety markers in a phase II study of metastatic XXXX treated with aflibercept in the first-line setting.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity901 :: ('MESH:C030110', 'Chemical') :: ['oxaliplatin'] @entity7 :: ('7422', 'Gene') :: ['vascular endothelial growth factor', 'VEGF'] @entity984 :: ('3845', 'Gene') :: ['KRAS'] @entity687 :: ('3576', 'Gene') :: ['IL8'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer'] @entity8497 :: ('4893', 'Gene') :: ['NRAS'] @entity10241 :: ('5295', 'Gene') :: ['PIK3R1'] @entity817 :: ('673', 'Gene') :: ['BRAF'] @entity23877 :: ('7423', 'Gene') :: ['VEGFB'] @entity10160 :: ('5290', 'Gene') :: ['PIK3CA']
@entity14 :: (MESH:D015179,Disease) :: ['colorectal cancer']
