Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab.
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.



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.



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.



REGARD exploratory analyses did not identify a strong potentially predictive biomarker of ramucirumab efficacy; however, statistical power was limited.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
Charles S
CS
Fuchs
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona 08035, Spain.
Josep
J
Tabernero
Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno 656 53, Czech Republic.
Jiří
J
Tomášek
Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK.
Ian
I
Chau
Onkologicka klinika, Lekarska fakulta Univerzity Palackeho a Fakultni nemocnice, I.P. Pavlova, 6, Olomouc 779 00, Czech Republic.
Bohuslav
B
Melichar
Brown University Oncology Research Group, 164 Summit Avenue, Fain 3, Providence, Rhode Island 02906, USA.
Howard
H
Safran
Centre Hospitalier de Montréal, 1560 Sherbrooke East St, Montreal, Quebec H2L4M1, Canada.
Mustapha A
MA
Tehfe
Spitalul Judetean de Urgenta, Strada George Coşbuc 31, Baia Mare 430031, Romania.
Dumitru
D
Filip
State Budgetary Educational Institution of Higher Professional Education (SBEIHPE), Northwest State Medical University na II Mechnikov, Ministry of Healthcare of the Russian Federation, Russia.
Eldar
E
Topuzov
Hospital da Cida de Passo Fundo, Rua Tiradentes, 295 Centro, Passo Fundo, 99010-260, Brazil.
Luis
L
Schlittler
Medisprof SRL, P-ta 1 Mai Nr 3, Cluj 400058, Romania.
Anghel Adrian
AA
Udrea
Hospital Herrera Llerandi, 6 Avenida, Guatemala City, Guatemala.
William
W
Campbell
Sir Anthony Mamo Oncology Centre, Msida, Malta.
Stephen
S
Brincat
Lilly Deutschland GmbH, Werner-Reimers-Straße 2, Bad Homburg vor der Höhe 61352, Germany.
Michael
M
Emig
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Symantha A
SA
Melemed
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Rebecca R
RR
Hozak
Eli Lilly and Company, 440 Route 22 East, Bridgewater, New Jersey 08807, USA.
David
D
Ferry
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
C William
CW
Caldwell
The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, Houston, Texas 77030, USA.
Jaffer A
JA
Ajani
D000230:Adenocarcinoma / Q000097:blood / Q000737:chemistry / Q000188:drug therapy*; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000097:blood*; D012189:Retrospective Studies; D016037:Single-Blind Method; D013274:Stomach Neoplasms / Q000097:blood / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000037:antagonists & inhibitors*; D042442:Vascular Endothelial Growth Factors / Q000097:blood*; D000096662:Ramucirumab
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D042442:Vascular Endothelial Growth Factors; D000096662:Ramucirumab; C508053:ERBB2 protein, human; C000588866:KDR protein, human