TY - JOUR
T1 - Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab
AU - Fuchs, Charles S.
AU - Tabernero, Josep
AU - Tomášek, Jiří
AU - Chau, Ian
AU - Melichar, Bohuslav
AU - Safran, Howard
AU - Tehfe, Mustapha A.
AU - Filip, Dumitru
AU - Topuzov, Eldar
AU - Schlittler, Luis
AU - Udrea, Anghel Adrian
AU - Campbell, William
AU - Brincat, Stephen
AU - Emig, Michael
AU - Melemed, Symantha A.
AU - Hozak, Rebecca R.
AU - Ferry, David
AU - Caldwell, C. William
AU - Ajani, Jaffer A.
N1 - Publisher Copyright:
© 2016 Cancer Research UK.
PY - 2016/10/11
Y1 - 2016/10/11
N2 - 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.
AB - 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.
KW - REGARD
KW - VEGFR2
KW - angiogenesis
KW - antibody
KW - biomarkers
KW - gastric carcinoma
KW - gastroesophageal carcinoma
KW - ramucirumab
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U2 - 10.1038/bjc.2016.293
DO - 10.1038/bjc.2016.293
M3 - Article
C2 - 27623234
AN - SCOPUS:84987622630
SN - 0007-0920
VL - 115
SP - 974
EP - 982
JO - British journal of cancer
JF - British journal of cancer
IS - 8
ER -