Correlation of extended RAS and @entity10160 gene mutation status with outcomes from the phase III AGITG MAX STUDY involving @entity416 alone or in combination with bevacizumab plus or minus @entity1138 in advanced XXXX .

@entity1 @entity416 @entity3012 @entity470 @entity5 @entity1138 @entity984 @entity406 @entity7097 @entity14 @entity10160
BACKGROUND: Mutations affecting RAS genes are now established predictive markers of nonresponse to anti- @entity470 antibodies in advanced @entity14 . This analysis assessed the prognostic and predictive impact of extended RAS and @entity10160 gene mutation status in @entity1 receiving @entity416 plus or minus bevacizumab (  @entity1138 ) in the randomised phase III MAX study. METHODS: DNA was extracted from archival macrodissected @entity406 -fixed paraffin-embedded @entity5 tissue. Mutation status was determined using pyrosequencing, confirmed with Sanger sequencing (for equivocal RAS) and correlated with efficacy outcomes. Predictive analyses were undertaken using a test for interaction involving both C vs CB+CBM. RESULTS: Of the available 280 of the 471 (59.4%) @entity1 , mutations in @entity984 exons 2, 3 and 4 and NRAS 2, 3 and 4 were as follows: 32%, 2.9%, 2.2%, 1.4%, 0.7% and 0% (total RAS MT 39%). The @entity10160 MT rate was 7.5% exon 9 and 3.6% exon 20. Extended RAS gene mutation status ( @entity7097 vs MT) had no prognostic impact for PFS (HR 0.91 (0.71-1.17)) or @entity3012 (HR 0.95 (0.71-1.25)). The RAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS (HR 0.56 (0.37-0.85) for RAS MT and HR 0.69 (0.5-0.97) for RAS @entity7097 ; P for interaction 0.50). The @entity10160 mutation was neither predictive for bevacizumab effect nor prognostic. CONCLUSION: Of @entity984 exon 2 @entity7097 @entity1 , 10% had additional RAS mutations. Neither all RAS gene mutation status nor @entity10160 mutation status was prognostic for PFS or @entity3012 , or predictive of bevacizumab outcome in @entity1 with advanced @entity14 .
