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

Autor: Fuchs CS; Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA., Tabernero J; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona 08035, Spain., Tomášek J; Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno 656 53, Czech Republic., Chau I; Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK., Melichar B; Onkologicka klinika, Lekarska fakulta Univerzity Palackeho a Fakultni nemocnice, I.P. Pavlova, 6, Olomouc 779 00, Czech Republic., Safran H; Brown University Oncology Research Group, 164 Summit Avenue, Fain 3, Providence, Rhode Island 02906, USA., Tehfe MA; Centre Hospitalier de Montréal, 1560 Sherbrooke East St, Montreal, Quebec H2L4M1, Canada., Filip D; Spitalul Judetean de Urgenta, Strada George Coşbuc 31, Baia Mare 430031, Romania., Topuzov E; State Budgetary Educational Institution of Higher Professional Education (SBEIHPE), Northwest State Medical University na II Mechnikov, Ministry of Healthcare of the Russian Federation, Russia., Schlittler L; Hospital da Cida de Passo Fundo, Rua Tiradentes, 295 Centro, Passo Fundo, 99010-260, Brazil., Udrea AA; Medisprof SRL, P-ta 1 Mai Nr 3, Cluj 400058, Romania., Campbell W; Hospital Herrera Llerandi, 6 Avenida, Guatemala City, Guatemala., Brincat S; Sir Anthony Mamo Oncology Centre, Msida, Malta., Emig M; Lilly Deutschland GmbH, Werner-Reimers-Straße 2, Bad Homburg vor der Höhe 61352, Germany., Melemed SA; Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA., Hozak RR; Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA., Ferry D; Eli Lilly and Company, 440 Route 22 East, Bridgewater, New Jersey 08807, USA., Caldwell CW; Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA., Ajani JA; The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, Houston, Texas 77030, USA.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2016 Oct 11; Vol. 115 (8), pp. 974-982. Date of Electronic Publication: 2016 Sep 13.
DOI: 10.1038/bjc.2016.293
Abstrakt: 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.
Competing Interests: IC, BM, MAT, JT report speaker honoraria from Lilly and non-Lilly pharmaceutical companies. JAA, IC report a commercial research grant. IC, CSF, JTa, MAT, JTo report serving on the Advisory Board for Eli Lilly and/or other companies. CWC, ME, DF, RRH, SAM are employees of Eli Lilly and Company. The remaining authors declare no conflict of interest.
Databáze: MEDLINE
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