Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab.
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ICR Authors
Authors
Fuchs, CS
Tabernero, J
Tomášek, J
Chau, I
Melichar, B
Safran, H
Tehfe, MA
Filip, D
Topuzov, E
Schlittler, L
Udrea, AA
Campbell, W
Brincat, S
Emig, M
Melemed, SA
Hozak, RR
Ferry, D
Caldwell, CW
Ajani, JA
Tabernero, J
Tomášek, J
Chau, I
Melichar, B
Safran, H
Tehfe, MA
Filip, D
Topuzov, E
Schlittler, L
Udrea, AA
Campbell, W
Brincat, S
Emig, M
Melemed, SA
Hozak, RR
Ferry, D
Caldwell, CW
Ajani, JA
Document Type
Journal Article
Date
2016-10
Date Accepted
2016-08-16
Date Available
Abstract
Background Angiogenesis inhibition is an important strategy for cancer treatment. Ramucirumab, a human IgG1 monoclonal antibody that targets VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C, -D binding and endothelial cell proliferation. To attempt to identify prognostic and predictive biomarkers, retrospective analyses were used to assess tumour (HER2, VEGFR2) and serum (VEGF-C and -D, and soluble (s) VEGFR1 and 3) biomarkers in phase 3 REGARD patients with metastatic gastric/gastroesophageal junction carcinoma.Methods A total of 152 out of 355 (43%) patients randomised to ramucirumab or placebo had ⩾1 evaluable biomarker result using VEGFR2 immunohistochemistry or HER2, immunohistochemistry or FISH, of blinded baseline tumour tissue samples. Serum samples (32 patients, 9%) were assayed for VEGF-C and -D, and sVEGFR1 and 3.Results None of the biomarkers tested were associated with ramucirumab efficacy at a level of statistical significance. High VEGFR2 endothelial expression was associated with a non-significant prognostic trend toward shorter progression-free survival (high vs low HR=1.65, 95% CI=0.84,3.23). Treatment with ramucirumab was associated with a trend toward improved survival in both high (HR=0.69, 95% CI=0.38, 1.22) and low (HR=0.73, 95% CI=0.42, 1.26) VEGFR2 subgroups. The benefit associated with ramucirumab did not appear to differ by tumoural HER2 expression.Conclusions REGARD exploratory analyses did not identify a strong potentially predictive biomarker of ramucirumab efficacy; however, statistical power was limited.
Citation
British journal of cancer, 2016, 115 (8), pp. 974 - 982
Source Title
Publisher
ISSN
0007-0920
eISSN
1532-1827