Fuchs, CharlesTabernero, JosepTomášek, JiříChau, IanMelichar, BohuslavSafran, HowardTehfe, Mustapha AFilip, DumitruTopuzov, EldarSchlittler, LuisUdrea, Anghel AdrianCampbell, WilliamBrincat, StephenEmig, MichaelMelemed, Symantha AHozak, Rebecca RFerry, DavidCaldwell, C WilliamAjani, Jaffer A2016-11-182016Fuchs, C. S., J. Tabernero, J. Tomášek, I. Chau, B. Melichar, H. Safran, M. A. Tehfe, et al. 2016. “Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab.” British Journal of Cancer 115 (8): 974-982. doi:10.1038/bjc.2016.293. http://dx.doi.org/10.1038/bjc.2016.293.0007-0920http://nrs.harvard.edu/urn-3:HUL.InstRepos:29408276Background: 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.en-USramucirumabgastric carcinomagastroesophageal carcinomabiomarkersVEGFR2antibodyangiogenesisREGARDJournal Article2016-11-1810.1038/bjc.2016.293