Prognostic and Predictive Value of Tumor Vascular Endothelial Growth Factor Gene Amplification in Metastatic Breast Cancer Treated with Paclitaxel with and without Bevacizumab; Results from ECOG 2100 Trial

Medicine, Indiana University Melvin and Bren Simon Cancer Center.
Clinical Cancer Research (Impact Factor: 8.72). 01/2013; 19(5). DOI: 10.1158/1078-0432.CCR-12-3029
Source: PubMed


Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here.

Experimental design:
E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. FISH to assess gene amplification status for VEGFA was conducted on paraffin-embedded tumors from 363 patients in E2100. Evaluation for association between amplification status and outcomes was conducted.

Estrogen receptor (ER)+ or progesterone receptor (PR)+ tumors were less likely to have VEGFA amplification than ER/PR- tumors (P = 0.020). VEGFA amplification was associated with worse OS (20.2 vs. 25.3 months; P = 0.013) in univariate analysis with a trend for worse OS in multivariate analysis (P = 0.08). There was a significant interaction between VEGFA amplification, hormone receptor status, and study arm. Patients with VEGFA amplification and triple-negative breast cancers (TNBC) or HER2 amplification had inferior OS (P = 0.047); amplification did not affect OS for those who were ER+ or PR+ and HER2-. Those who received bevacizumab with VEGFA amplification had inferior progression-free survival (PFS; P = 0.010) and OS (P = 0.042); no association was seen in the control arm. Test for interaction between study arm and VEGFA amplification with OS was not significant.

VEGFA amplification in univariate analysis was associated with poor outcomes; this was particularly prominent in HER2+ or TNBCs. Additional studies are necessary to confirm the trend for poor OS seen on multivariate analysis for patients treated with bevacizumab.

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Available from: Guanglong Jiang, Jan 01, 2015
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    • "Two additional genotypes (VEGF-634CC and VEGF-1498TT) showed strong correlation with less Grade 3/4 hypertension in the combination arm when compared with all other genotypes combined (P = 0.005 and P = 0.022, respectively). In another correlative study of E2100, the ability for tumor VEGFA amplification to predict outcome was conducted (55). Patients with tumor VEGFA amplification had significantly worse median PFS (7.8 vs. 8.3 months; P = 0.040) and median OS (20.2 vs. 25.3 months; P = 0.013) than those whose tumors did not exhibit amplification (Table 3). "
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