Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.
Regorafenib monotherapy is a potential option for metastatic colorectal cancer patients. However, the lack of predictive factors and the severe toxicities related to treatment have made its use in clinical practice challenging. Polymorphisms of VEGF and its receptor (VEGFR) genes might regulate angiogenesis and thus potentially influence outcome during anti-angiogenesis treatment such as regorafenib. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. We retrospectively collected clinical data and samples (tumour or blood) of 138 metastatic colorectal cancer patients treated with regorafenib. We analysed the correlation of different VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs) with patients' progression-free survival (PFS) and overall survival (OS). Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS. Among clinical factors only ECOG PS was independently correlated with OS, whereas no correlation with PFS was evident. Grouping together those results allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of optimal candidates for regorafenib therapy.
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Riccardo
R
Giampieri
Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Università di Pisa, Pisa, Italy.
Lisa
L
Salvatore
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Michela
M
Del Prete
Medical Oncology, Fondazione Poliambulanza Brescia, Brescia, Italy.
Tiziana
T
Prochilo
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Marco
M
D'Anzeo
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Cristian
C
Loretelli
Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Università di Pisa, Pisa, Italy.
Fotios
F
Loupakis
Medical Oncology, Azienda Ospedaliera di Udine, Università di Udine, Udine, Italy.
Giuseppe
G
Aprile
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Elena
E
Maccaroni
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Kalliopi
K
Andrikou
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Maristella
M
Bianconi
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Alessandro
A
Bittoni
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Luca
L
Faloppi
Medical Oncology, Azienda Ospedaliera Universitaria di Cagliari, Università di Cagliari, Cagliari, Italy.
Laura
L
Demurtas
Pathology, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Rodolfo
R
Montironi
Pathology, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Marina
M
Scarpelli
Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Università di Pisa, Pisa, Italy.
Alfredo
A
Falcone
Medical Oncology, Fondazione Poliambulanza Brescia, Brescia, Italy.
Alberto
A
Zaniboni
Medical Oncology, Azienda Ospedaliera Universitaria di Cagliari, Università di Cagliari, Cagliari, Italy.
Mario
M
Scartozzi
Medical Oncology, Translational Research Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Stefano
S
Cascinu
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000071184:Pharmacogenomic Variants; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011725:Pyridines / Q000008:administration & dosage* / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics*
D020533:Angiogenesis Inhibitors; D010671:Phenylurea Compounds; D011725:Pyridines; D017468:Receptors, Fibroblast Growth Factor; C467484:VEGFA protein, human; C467486:VEGFC protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; C559147:regorafenib