AUTHOR=Jantus-Lewintre Eloisa , Massutí Sureda Bartomeu , González Larriba José Luis , Rodríguez-Abreu Delvys , Juan Oscar , Blasco Ana , Dómine Manuel , Provencio Pulla Mariano , Garde Javier , Álvarez Rosa , Maestu Inmaculada , Pérez de Carrión Ramón , Artal Ángel , Rolfo Christian , de Castro Javier , Guillot Mónica , Oramas Juana , de las Peñas Ramón , Ferrera Lioba , Martínez Natividad , Serra Òlbia , Rosell Rafael , Camps Carlos 

TITLE=Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.695038

DOI=10.3389/fonc.2021.695038

ISSN=2234-943X

ABSTRACT=<p>Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. <italic>VEGFR-1</italic> rs9582036 variants AA/AC were associated with increased progression-free survival (<italic>p</italic> = 0.012 and <italic>p</italic> = 0.035, respectively), and with improved overall survival (<italic>p</italic> = 0.019) with respect to CC allele. Patients with <italic>VEGF-A</italic> rs3025039 harboring allele TT had also reduced mortality risk (<italic>p</italic> = 0.049) compared with the CC allele. The <italic>VEGF-A</italic> rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (<italic>p</italic> = 0.036). In conclusion, in this prospective study, genetic variants in <italic>VEGFR-1</italic> and <italic>VEGF-A</italic> and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy.</p>