Biomarkers of Bevacizumab Efficacy in Advanced Gastric Cancer Identified

Share this content:

(ChemotherapyAdvisor) – AVAGAST, the first and largest randomized Phase 3 trial to evaluate the efficacy of bevacizumab with a comprehensive prospective biomarker analysis, has found that baseline plasma levels of VEGF-A and baseline tumor expression of neuropilin-1 are strong biomarker candidates to predict clinical outcome in patients with advanced gastric cancer, according to a study in the Journal of Clinical Oncology online May 7.

AVAGAST was a global, randomized, double-blind Phase 3 study that compared bevacizumab plus chemotherapy (n=387) vs. chemotherapy alone (n=387) in treatment-naïve patients with locally advanced or metastatic gastric cancer. Results of this study showed that compared with placebo, adding bevacizumab to chemotherapy improved progression-free survival and tumor response rate but not overall survival (12.1 vs. 10.1 months; HR, 0.87; P=0.1002), the primary endpoint.

The AVAGAST trial included a mandatory biomarker program that gathered blood samples and tissue to examine the hypotheses that plasma and tumor tissue markers involved in the VEGF pathway may have predictive value for bevacizumab efficacy in gastric cancer. 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).

Plasma was available from 712 patients (92%), and tumor samples from 727 (94%). “Baseline plasma VEGF-A levels and tumor neuropilin-1 expression were identified as potential predictors of bevacizumab efficacy,” they found. Those with high baseline plasma VEGF-A levels showed a trend toward improved overall survival (HR, 0.72) vs. low VEGF-A levels (HR, 1.01; interaction P=0.07). Patients with low baseline expression of neuropilin-1 also showed a trend toward improved overall survival (HR, 0.75) vs. those with high neuropilin-1 expression (HR, 1.07; interaction P=0.06). “For both biomarkers, subgroup analyses demonstrated significance only in patients from non-Asian regions,” they wrote.

“Prospective studies are required to further characterize these markers,” the investigators noted, adding that “collection of data for plasma VEGF-A and tumor neuropilin-1 should be integrated prospectively into new gastric cancer studies of bevacizumab to validate the findings from AVAGAST.”

Abstract

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters



Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs