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.

Brown University Oncology Research Group 164 Summit Avenue Fain 3 Providence Rhode Island 02906 USA

Centre Hospitalier de Montréal 1560 Sherbrooke East St Montreal Quebec H2L4M1 Canada

Dana Farber Cancer Institute Harvard Medical School Boston Massachusetts 02215 USA

Eli Lilly and Company 440 Route 22 East Bridgewater New Jersey 08807 USA

Eli Lilly and Company Lilly Corporate Center Indianapolis Indiana 46285 USA

Hospital da Cida de Passo Fundo Rua Tiradentes 295 Centro Passo Fundo 99010 260 Brazil

Hospital Herrera Llerandi 6 Avenida Guatemala City Guatemala

Lilly Deutschland GmbH Werner Reimers Straße 2 Bad Homburg vor der Höhe 61352 Germany

Masaryk Memorial Cancer Institute Faculty of Medicine Masaryk University Brno 656 53 Czech Republic

Medisprof SRL P ta 1 Mai Nr 3 Cluj 400058 Romania

Onkologicka klinika Lekarska fakulta Univerzity Palackeho a Fakultni nemocnice 1 P Pavlova 6 Olomouc 779 00 Czech Republic

Royal Marsden Hospital Downs Road Sutton Surrey SM2 5PT UK

Sir Anthony Mamo Oncology Centre Msida Malta

Spitalul Judetean de Urgenta Strada George Coşbuc 31 Baia Mare 430031 Romania

State Budgetary Educational Institution of Higher Professional Education Northwest State Medical University na 2 Mechnikov Ministry of Healthcare of the Russian Federation Russia

The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Unit 426 Houston Texas 77030 USA

Vall d'Hebron University Hospital and Institute of Oncology Universitat Autònoma de Barcelona Barcelona 08035 Spain

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