Open AccessExploration of potential prognostic biomarkers in aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer
Author(s) -
Hamaguchi Tetsuya,
Denda Tadamichi,
Kudo Toshihiro,
Sugimoto Naotoshi,
Ura Takashi,
Yamazaki Kentaro,
Fujii Hirofumi,
Kajiwara Takeshi,
Nakajima Takako Eguchi,
Takahashi Shin,
Otsu Satoshi,
Komatsu Yoshito,
Nagashima Fumio,
Moriwaki Toshikazu,
Esaki Taito,
Sato Takeo,
Itabashi Michio,
Oki Eiji,
Sasaki Toru,
Chiron Marielle,
Yoshino Takayuki
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14198
Subject(s) - folfiri , medicine , aflibercept , oncology , colorectal cancer , vascular endothelial growth factor , cancer , bevacizumab , irinotecan , chemotherapy , vegf receptors
Aflibercept plus 5‐fluorouracil/levofolinate/irinotecan (FOLFIRI) is a second‐line treatment for metastatic colorectal cancer. This ancillary exploratory analysis of data in Japanese people was aimed at exploring the relationship between a set of potential prognostic biomarkers and efficacy endpoints following aflibercept plus FOLFIRI therapy. Sixty‐two patients with metastatic colorectal cancer received aflibercept (4 mg/kg) plus FOLFIRI every 2 weeks. Seventy‐eight potential protein biomarkers were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor‐stroma interaction. Plasma levels of biomarkers at baseline and at pre‐dose 3 (day 1 of treatment cycle 3) were measured in all patients by ELISA. Relationships between these levels and efficacy endpoints were assessed. Ten potential biomarkers had a ±30% change from baseline to pre‐dose 3 (adjusted P < .001), with the greatest changes occurring in placental growth factor (median: +4716%) and vascular endothelial growth factor receptor 1 (+2171%). Baseline levels of eight potential biomarkers correlated with overall survival in a univariate Cox regression analysis: extracellular newly identified receptor for advanced glycation end‐products binding protein, insulin‐like growth factor‐binding protein 1, interleukin‐8, kallikrein 5, pulmonary surfactant‐associated protein D, tissue inhibitor of metalloproteinases 1, tenascin‐C, and tumor necrosis factor receptor 2. None correlated with progression‐free survival or maximum tumor shrinkage. Pre‐dose 3 levels did not correlate with any efficacy endpoints. Preliminary data show that these eight biomarkers could be associated with overall survival. ClinicalTrials.gov identifier: NCT01882868.