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

American Society of Clinical Oncology (ASCO) - Tập 30 Số 17 - Trang 2119-2127 - 2012
Eric Van Cutsem1, Sanne de Haas1, Yoon‐Koo Kang1, Atsushi Ohtsu1, Niall C. Tebbutt1, Jianming Xu1, Wei Peng Yong1, Bernd Langer1, Paul Delmar1, Stefan Scherer1, Manish A. Shah1
1Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium; Sanne de Haas and Paul Delmar, F. Hoffmann-La Roche, Basel, Switzerland; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Atsushi Ohtsu, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Niall C. Tebbutt, Austin Health, Heidelberg, Victoria, Australia; Jian Ming Xu, PLA 307 Hospital, Fengtai District, Beijing, China; Wei Peng Yong, National University Hospital, Singapore; Bernd...

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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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American Society of Clinical Oncology (ASCO)

Tập 30 Số 17

2119-2127

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