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

Autoři	FUCHS Charles S. TABERNERO Josep TOMÁŠEK Jiří CHAU Ian MELICHAR Bohuslav SAFRAN Howard TEHFE Mustapha A. FILIP Dumitru TOPUZOV Eldar SCHLITTLER Luis UDREA Anghel Adrian CAMPBELL William BRINCAT Stephen EMIG Michael MELEMED Symantha A. HOZAK Rebecca R. FERRY David CALDWELL C. William AJANI Jaffer A.
Rok publikování	2016
Druh	Článek v odborném periodiku
Časopis / Zdroj	British Journal of Cancer
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
www	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061911/pdf/bjc2016293a.pdf
Doi	http://dx.doi.org/10.1038/bjc.2016.293
Obor	Onkologie a hematologie
Klíčová slova	ramucirumab; gastric carcinoma; gastroesophageal carcinoma; biomarkers; VEGFR2; antibody; angiogenesis; REGARD
Popis	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.