ECOG E2100 - Cancer Therapy Evaluation Program (CTEP)

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<strong>E2100</strong> correlative study: Methods • 673 eligible pts & 623 dz progression (11/07) • DNA extracted from paraffin embedded tumor blocks (genotype-363; VEGF IHC-377; VEGFR2-341) – ~50% from experimental arm • Genotyping of candidate SNPs (Real time-PCR) – VEGF: -2578 C/A, -1498 C/T, -1154 G/A, -634 G/C, 936C/T – VEGFR-2: V297I & Q472H • IHC for VEGF & VEGFR-2 tumor expression
VEGF -2578 AA & -1154 AA genotypes associated with improved OS in SNP Genotype comparison (median OS in mo & freq) combination arm HR CI Pvalue VEGF-2578 CA (24.4; 42.6%) vs. AA (37.0; 20.8%) 1.78 (98.3%=0.96, 3.32) 0.026 CC (22.2; 37.6%) vs. AA (37.0; 21%) 1.70 (98.3%=0.91, 3.17) 0.043 CC (22.2; 37.6%) vs. CA (24.4; 42.6%) 0.99 (98.3=0.62, 1.58) 0.95 AA vs. CA+CC 0.58 (95%-0.36, 0.93) 0.023 VEGF-1154 GG (22.3; 56.9%) vs. GA (29.8; 38.8%) 1.60 (98.3%=0.98, 2.60) 0.022 GG (22.3; 56.95) vs. AA (46.5; 9.4%) 2.69 (98.3%=1.10, 6.59) 0.008 GA (29.8; 38.8%) vs. AA (46.5; 9.4%) 1.68 (98.3%=0.66, 4.30) 0.19 AA vs. GA vs. GG 0.62 (95%=0.46, 0.83) 0.001 Schneider et al; SABCS, 2007
Page 1 and 2: ECOG Pharmacogenomics: Anti-Angioge
Page 3 and 4: Genetic variability impacts angioge
Page 5 and 6: Bevacizumab in breast cancer-E2100:
Page 7 and 8: PFS Proportion 1.0 0.8 0.6 0.4 0.2
Page 9 and 10: GOOD NEWS=all subgroups gained bene
Page 11 and 12: Germline genetic variation in tumor
Page 13 and 14: Candidate SNPs meet fundamental •
Page 15: Genetic variability in tumor angiog
Page 19 and 20: Genetic variability of VEGF predict
Page 21 and 22: VEGF genotypes may be associated wi
Page 23 and 24: VEGF Promoter & 5’-UTR Re-sequenc
Page 25 and 26: Caucasians African-Americans 76% 70
Page 27 and 28: Acknowledgements • David Flockhar

ECOG E2100 - Cancer Therapy Evaluation Program (CTEP)

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