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Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Biomarker Evaluation From the AVAGAST Randomized Phase III Trial
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.
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Metadata
- Authors
- Van Cutsem, E., de Haas, S., Kang, Y.-K., Ohtsu, A., Tebbutt, N. C., Ming Xu, J., Peng Yong, W., Langer, B., Delmar, P., Scherer, S. J., & Shah, M. A.
- Venue
- Journal of Clinical Oncology
- Published
- 2012-06-10
- Volume
- 30
- Issue
- 17
- Pages
- 2119-2127
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2109491042
- Cited by
- 477
- References
- 28
- FWCI
- 51.94
- Type
- journal article
- Language
- en
- Open access
- closed
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- Van Cutsem, E., de Haas, S., Kang, Y.-K., Ohtsu, A., Tebbutt, N. C., Ming Xu, J., Peng Yong, W., Langer, B., Delmar, P., Scherer, S. J., & Shah, M. A. (2012). Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Biomarker Evaluation From the AVAGAST Randomized Phase III Trial. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2011.39.9824
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