Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab
Fuchs, Charles S. (Harvard Medical School)
Tabernero, Josep (Vall d'Hebron Institut d'Oncologia)
Tomášek, Jiří (Masaryk University (Czech Republic))
Chau, Ian (Royal Marsden Hospital (Regne Unit))
Melichar, Bohuslav (Univerzity Palackeho a Fakultni nemocnice (Czech Republic))
Safran, Howard (Brown University Oncology Research Group (USA))
Tehfe, Mustapha A. (Centre Hospitalier de Montréal (Canada))
Filip, Dumitru (Spitalul Judetean de Urgenta (Romania))
Topuzov, Eldar (Northwest State Medical University na II Mechnikov)
Schlittler, Luis (Hospital da Cida de Passo Fundo (Brasil))
Udrea, Anghel Adrian (Medisprof SRL (Romania))
Campbell, William (Hospital Herrera Llerandi (Guatemala))
Brincat, Stephen (Sir Anthony Mamo Oncology Centre (Malta))
Emig, Michael (Lilly Deutschland GmbH (Germany))
Melemed, Symantha A. (Lilly Corporate Center (USA))
Hozak, Rebecca R. (Lilly Corporate Center (USA))
Ferry, David (Lilly Corporate Center (USA))
Caldwell, C. William (Lilly Corporate Center (USA))
Ajani, Jaffer A. (The University of Texas MD Anderson Cancer Center (USA))
Universitat Autònoma de Barcelona

Data:	2016
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Ramucirumab ; Gastric carcinoma ; Gastroesophageal carcinoma ; Biomarkers ; VEGFR2 ; Antibody ; Angiogenesis ; REGARD
Publicat a:	British journal of cancer, Vol. 115, Issue 8 (October 2016) , p. 974-982, ISSN 1532-1827

DOI: 10.1038/bjc.2016.293
PMID: 27623234

9 p, 1.1 MB

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