AUTHOR=D’Alessandro Rosalba , Refolo Maria Grazia , Schirizzi Annalisa , De Leonardis Giampiero , Donghia Rossella , Guerra Vito , Giannelli Gianluigi , Lolli Ivan Roberto , Laterza Maria Maddalena , De Vita Ferdinando , Messa Caterina , Lotesoriere Claudio 

TITLE=Variations in Circulating Levels of Angiopoietin-2 Over Time Are Predictive of Ramucirumab–Paclitaxel Therapy Outcome in Advanced Gastric Cancer: Results of Prospective Study

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.862116

DOI=10.3389/fonc.2022.862116

ISSN=2234-943X

ABSTRACT=The combination of Paclitaxel and Ramucirumab is the second-line therapy of choice in treatment of advanced Gastric Cancer. To date no biomarkers are available in Gastric Cancer to predict the outcome of antiangiogenic therapy. The present prospective study included 35 patients undergoing second-line therapy with Ramucirumab and Paclitaxel. Analysis of the levels of circulating angiogenic biomarkers was performed at multiple time points. The population was divided into "control-disease” and "progressive-disease” groups. Comparative analyses in the two groups at third cycle of therapy, revealed significant different results for VEGFC and Angiopoietin-2 both involved in angiogenesis and lymphangiogenesis. VEGFC increased in the progressive-disease group while it decreased in the control-disease group. This decrease persisted beyond the third cycle and it was statistically significant compared to basal level in patients with longer Progression Free Survival. Angiopoietin-2 decreased significantly after two months of therapy. At progression time there was a significant increase in VEGFC and Angiopoietin-2 suggesting the activation pathways counteracting the blockade of VEGFR2 by Ramucirumab. Overall results showed that a greater change in VEGFC and Angiopoietin-2 levels measured at the beginning of the third cycle of therapy corresponded to a lower risk of progression and thus to a longer Progression Free Survival.