Effect of aflibercept plus FOLFIRI and potential efficacy biomarkers in patients with metastatic colorectal cancer: the POLAF trial

Background Aflibercept is an antiangiogenic drug against metastatic colorectal cancer (mCRC) combined with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI); however, no antiangiogenic biomarker has yet been validated. We assessed aflibercept plus FOLFIRI, investigating the biomarker role of baseline v...

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Published in:British journal of cancer 2022-04, Vol.126 (6), p.874-880
Main Authors: Élez, Elena, Gómez-España, María Auxiliadora, Grávalos, Cristina, García-Alfonso, Pilar, Ortiz-Morales, María José, Losa, Ferrán, Díaz, Inmaculada Alés, Graña, Begoña, Toledano-Fonseca, Marta, Valladares-Ayerbes, Manuel, Polo, Eduardo, Salgado, Mercedes, Martínez de Castro, Eva, Safont, María José, Salud, Antonieta, Ruiz-Casado, Ana, Tabernero, Josep, Riesco, María del Carmen, Rodriguez-Ariza, Antonio, Aranda, Enrique
Format: Article
Language:English
Subjects:
5-Fluorouracil
692/699/67/1504/1885
692/700/565/1436/1437
Angiotensin
Antiangiogenic agents
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers
Biomedical and Life Sciences
Biomedicine
Camptothecin - therapeutic use
Cancer Research
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - pathology
Disease control
Drug Resistance
Epidemiology
Fluorouracil - therapeutic use
Humans
Irinotecan
Irinotecan - therapeutic use
Leucovorin - therapeutic use
Metastases
Metastasis
Molecular Medicine
Oncology
Oxaliplatin
Patients
Peptidyl-dipeptidase A
Receptors, Vascular Endothelial Growth Factor - therapeutic use
Recombinant Fusion Proteins - therapeutic use
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - metabolism
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Summary:Background Aflibercept is an antiangiogenic drug against metastatic colorectal cancer (mCRC) combined with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI); however, no antiangiogenic biomarker has yet been validated. We assessed aflibercept plus FOLFIRI, investigating the biomarker role of baseline vascular endothelial growth factor A (VEGF-A) and angiotensin-converting enzyme (ACE). Methods Phase II trial in oxaliplatin-treated mCRC patients who received aflibercept plus FOLFIRI. The reported 135 ng/mL ACE cut-off was used and ROC analysis was performed to assess the optimal VEGF-A cut-off for progression-free survival (PFS). Overall survival (OS), time to progression (TTP), time to treatment failure (TTF), overall response rate (ORR) and disease control rate (DCR) were also assessed. Results In total, 101 patients were followed for a median of 12 (6–17) months. The 1941 pg/mL VEGF-A was an optimal cut-off, with a longer median PFS when VEGF-A was
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-021-01638-w