Abstract
72 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use; however, no validated biomarker has been available until today. The aim of this study is 1) to reveal the dynamics of plasma biomarkers, 2) to assess the associations between these baseline levels or dynamics and efficacy. Methods: Plasma samples were collected at three points: base line, day 8, and after disease progression. Nine kinds of plasma biomarker involved in angiogenesis were measured by means of ELISA. Progression-free survival (PFS) was estimated using Kaplan-Meier methods and compared using the log-rank test. Comparisons of plasma biomarker levels were performed using Mann-Whitney-U test. Results: Samples were collected from 35 patients. Among them, 25 patients were evaluated when analyzed and 6 patients showed disease progression at the first evaluation. In VEGF-A and PlGF, plasma biomarker levels of day 8 were dramatically elevated in all patients; Day8/ baseline ratios were 18.1 folds in VEGF-A and 19.3 folds in PlGF. On the other hand, Day8/ baseline ratio of VEGFR1 and NRP1 were 0.7 and 0.8, respectively. The others appeared to show variable change at day 8. In survival analysis, lower than median Day8/ baseline ratios of VEGF-A were significantly associated with longer PFS with 6.3 months in < median vs. 2.4 months in ≥ median (p = 0.004). In addition, patients with disease progression at the first evaluation by CT showed higher Day8/ baseline ratios of VEGF-C, Angiopoietin 1, and lower baseline NRP1 levels than those of patients with non-disease progression. Conclusions: Dramatic changes of biomarker levels at day 8 were observed among patients in each biomarker. These changes in VEGF-A, C, and Angiopoietin-1 may be candidate predictive marker of ramucirumab in Japanese patients with gastric cancer.
Published Version
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