Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Biomarker Evaluation From the AVAGAST Randomized Phase III Trial

Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A... Purpose: The AVAGAST study showed that adding bevacizumab to chemotherapy in patients with advanced gastric cancer improves progression-free survival and tumor response rate but not overall survival. To examine the hypothesis that angiogenic markers may have predictive value for bevacizumab efficacy in gastric cancer, AVAGAST included a prospective, mandatory biomarker program. Patients and Methods: Patients with previously untreated, locally advanced or metastatic gastric cancer were randomly assigned to bevacizumab (n = 387) or placebo (n = 387) in combination with chemotherapy. Blood and tumor tissue samples were collected at baseline. Prespecified biomarkers included plasma vascular endothelial growth factor-A (VEGF-A), protein expression of neuropilin-1, and VEGF receptors-1 and -2 (VEGFR-1 and VEGFR-2). Correlations between biomarkers and clinical outcomes were assessed by using a Cox proportional hazards model. Results: Plasma was available from 712 patients (92%), and tumor samples were available from 727 patients (94%). Baseline plasma VEGF-A levels and tumor neuropilin-1 expression were identified as potential predictors of bevacizumab efficacy. Patients with high baseline plasma VEGF-A levels showed a trend toward improved overall survival (hazard ratio [HR], 0.72; 95% CI, 0.57 to 0.93) versus patients with low VEGF-A levels (HR, 1.01; 95% CI, 0.77 to 1.31; interaction P = .07). Patients with low baseline expression of neuropilin-1 also showed a trend toward improved overall survival (HR, 0.75; 95% CI, 0.59 to 0.97) versus patients with high neuropilin-1 expression (HR, 1.07; 95% CI, 0.81 to 1.40; interaction P = .06). For both biomarkers, subgroup analyses demonstrated significance only in patients from non-Asian regions. Conclusion: Plasma VEGF-A and tumor neuropilin-1 are strong biomarker candidates for predicting clinical outcome in patients with advanced gastric cancer treated with bevacizumab. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Clinical Oncology Wolters Kluwer Health

Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Biomarker Evaluation From the AVAGAST Randomized Phase III Trial

Loading next page...
 
/lp/wolters-kluwer-health/bevacizumab-in-combination-with-chemotherapy-as-first-line-therapy-in-HdTtS1n1JW

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
Wolters Kluwer Health
Copyright
(C) 2012 American Society of Clinical Oncology
ISSN
0732-183X
eISSN
1527-7755
DOI
10.1200/JCO.2011.39.9824
Publisher site
See Article on Publisher Site

Abstract

Purpose: The AVAGAST study showed that adding bevacizumab to chemotherapy in patients with advanced gastric cancer improves progression-free survival and tumor response rate but not overall survival. To examine the hypothesis that angiogenic markers may have predictive value for bevacizumab efficacy in gastric cancer, AVAGAST included a prospective, mandatory biomarker program. Patients and Methods: Patients with previously untreated, locally advanced or metastatic gastric cancer were randomly assigned to bevacizumab (n = 387) or placebo (n = 387) in combination with chemotherapy. Blood and tumor tissue samples were collected at baseline. Prespecified biomarkers included plasma vascular endothelial growth factor-A (VEGF-A), protein expression of neuropilin-1, and VEGF receptors-1 and -2 (VEGFR-1 and VEGFR-2). Correlations between biomarkers and clinical outcomes were assessed by using a Cox proportional hazards model. Results: Plasma was available from 712 patients (92%), and tumor samples were available from 727 patients (94%). Baseline plasma VEGF-A levels and tumor neuropilin-1 expression were identified as potential predictors of bevacizumab efficacy. Patients with high baseline plasma VEGF-A levels showed a trend toward improved overall survival (hazard ratio [HR], 0.72; 95% CI, 0.57 to 0.93) versus patients with low VEGF-A levels (HR, 1.01; 95% CI, 0.77 to 1.31; interaction P = .07). Patients with low baseline expression of neuropilin-1 also showed a trend toward improved overall survival (HR, 0.75; 95% CI, 0.59 to 0.97) versus patients with high neuropilin-1 expression (HR, 1.07; 95% CI, 0.81 to 1.40; interaction P = .06). For both biomarkers, subgroup analyses demonstrated significance only in patients from non-Asian regions. Conclusion: Plasma VEGF-A and tumor neuropilin-1 are strong biomarker candidates for predicting clinical outcome in patients with advanced gastric cancer treated with bevacizumab.

Journal

Journal of Clinical OncologyWolters Kluwer Health

Published: Jun 10, 2012

References