Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100

Bryan P. Schneider, Molin Wang, Milan Radovich, George W. Sledge, Sunil Badve, Ann Thor, David A. Flockhart, Bradley Hancock, Nancy Davidson, Julie Gralow, Maura Dickler, Edith A. Perez, Melody Cobleigh, Tamara Shenkier, Susan Edgerton, Kathy D. Miller

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Abstract

Purpose: No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer. Patients and Methods: DNA was extracted from tumor blocks of patients from E2100. Three hundred sixty-three samples were available to evaluate associations between genotype and outcome. Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2. Testing for associations between each polymorphism and efficacy and toxicity was performed. Results: The VEGF-2578 AA genotype was associated with a superior median overall survival (OS) in the combination arm when compared with the alternate genotypes combined (hazard ratio = 0.58; 95% CI, 0.36 to 0.93; P = .023). The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm (hazard ratio = 0.62; 95% CI, 0.46 to 0.83; P = .001). Two additional genotypes, VEGF-634 CC and VEGF-1498 TT, were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined (P = .005 and P = .022, respectively). Conclusion: Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer.

Original languageEnglish
Pages (from-to)4672-4678
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number28
DOIs
StatePublished - Oct 1 2008

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Vascular Endothelial Growth Factor Receptor-2
Genetic Polymorphisms
Paclitaxel
Vascular Endothelial Growth Factor A
Breast Neoplasms
Genotype
Survival
Alleles
Hypertension
Safety Management
Bevacizumab
Neoplasms
Biomarkers
Drug Therapy
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer : ECOG 2100. / Schneider, Bryan P.; Wang, Molin; Radovich, Milan; Sledge, George W.; Badve, Sunil; Thor, Ann; Flockhart, David A.; Hancock, Bradley; Davidson, Nancy; Gralow, Julie; Dickler, Maura; Perez, Edith A.; Cobleigh, Melody; Shenkier, Tamara; Edgerton, Susan; Miller, Kathy D.

In: Journal of Clinical Oncology, Vol. 26, No. 28, 01.10.2008, p. 4672-4678.

Research output: Contribution to journalArticle

Schneider, Bryan P. ; Wang, Molin ; Radovich, Milan ; Sledge, George W. ; Badve, Sunil ; Thor, Ann ; Flockhart, David A. ; Hancock, Bradley ; Davidson, Nancy ; Gralow, Julie ; Dickler, Maura ; Perez, Edith A. ; Cobleigh, Melody ; Shenkier, Tamara ; Edgerton, Susan ; Miller, Kathy D. / Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer : ECOG 2100. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 28. pp. 4672-4678.
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abstract = "Purpose: No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer. Patients and Methods: DNA was extracted from tumor blocks of patients from E2100. Three hundred sixty-three samples were available to evaluate associations between genotype and outcome. Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2. Testing for associations between each polymorphism and efficacy and toxicity was performed. Results: The VEGF-2578 AA genotype was associated with a superior median overall survival (OS) in the combination arm when compared with the alternate genotypes combined (hazard ratio = 0.58; 95{\%} CI, 0.36 to 0.93; P = .023). The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm (hazard ratio = 0.62; 95{\%} CI, 0.46 to 0.83; P = .001). Two additional genotypes, VEGF-634 CC and VEGF-1498 TT, were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined (P = .005 and P = .022, respectively). Conclusion: Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer.",
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T1 - Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer

T2 - ECOG 2100

AU - Schneider, Bryan P.

AU - Wang, Molin

AU - Radovich, Milan

AU - Sledge, George W.

AU - Badve, Sunil

AU - Thor, Ann

AU - Flockhart, David A.

AU - Hancock, Bradley

AU - Davidson, Nancy

AU - Gralow, Julie

AU - Dickler, Maura

AU - Perez, Edith A.

AU - Cobleigh, Melody

AU - Shenkier, Tamara

AU - Edgerton, Susan

AU - Miller, Kathy D.

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Purpose: No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer. Patients and Methods: DNA was extracted from tumor blocks of patients from E2100. Three hundred sixty-three samples were available to evaluate associations between genotype and outcome. Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2. Testing for associations between each polymorphism and efficacy and toxicity was performed. Results: The VEGF-2578 AA genotype was associated with a superior median overall survival (OS) in the combination arm when compared with the alternate genotypes combined (hazard ratio = 0.58; 95% CI, 0.36 to 0.93; P = .023). The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm (hazard ratio = 0.62; 95% CI, 0.46 to 0.83; P = .001). Two additional genotypes, VEGF-634 CC and VEGF-1498 TT, were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined (P = .005 and P = .022, respectively). Conclusion: Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer.

AB - Purpose: No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer. Patients and Methods: DNA was extracted from tumor blocks of patients from E2100. Three hundred sixty-three samples were available to evaluate associations between genotype and outcome. Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2. Testing for associations between each polymorphism and efficacy and toxicity was performed. Results: The VEGF-2578 AA genotype was associated with a superior median overall survival (OS) in the combination arm when compared with the alternate genotypes combined (hazard ratio = 0.58; 95% CI, 0.36 to 0.93; P = .023). The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm (hazard ratio = 0.62; 95% CI, 0.46 to 0.83; P = .001). Two additional genotypes, VEGF-634 CC and VEGF-1498 TT, were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined (P = .005 and P = .022, respectively). Conclusion: Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer.

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