Exploration of potential prognostic biomarkers in aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer.

Abstract

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.

• Authors: Tetsuya Hamaguchi, Tadamichi Denda, Toshihiro Kudo, Naotoshi Sugimoto, Takashi Ura, Kentaro Yamazaki, Hirofumi Fujii, Takeshi Kajiwara, Takako Eguchi Nakajima, Shin Takahashi, Satoshi Otsu, Yoshito Komatsu, Fumio Nagashima, Toshikazu Moriwaki, Taito Esaki, Takeo Sato, Michio Itabashi, Eiji Oki, Toru Sasaki, Marielle Chiron, Takayuki Yoshino
• Journal: Cancer science (Cancer Sci) Vol. 110 Issue 11 Pg. 3565-3572 (Nov 2019) ISSN: 1349-7006 [Electronic] England
• PMID: 31520559 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Biomarkers, Tumor
• IGFBP1 protein, human
• Insulin-Like Growth Factor Binding Protein 1
• Interleukin-8
• Pulmonary Surfactant-Associated Protein D
• Receptor for Advanced Glycation End Products
• Receptors, Tumor Necrosis Factor, Type II
• Recombinant Fusion Proteins
• TIMP1 protein, human
• TNC protein, human
• Tenascin
• Tissue Inhibitor of Metalloproteinase-1
• Placenta Growth Factor
• aflibercept
• Receptors, Vascular Endothelial Growth Factor
• Vascular Endothelial Growth Factor Receptor-1
• KLK5 protein, human
• Kallikreins
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Asian People
• Biomarkers, Tumor (blood)
• Camptothecin (analogs & derivatives, therapeutic use)
• Colonic Neoplasms (blood, drug therapy, mortality, pathology)
• Fluorouracil (therapeutic use)
• Humans
• Insulin-Like Growth Factor Binding Protein 1 (blood)
• Interleukin-8 (blood)
• Japan
• Kallikreins (blood)
• Leucovorin (therapeutic use)
• Placenta Growth Factor (blood)
• Prognosis
• Progression-Free Survival
• Prospective Studies
• Pulmonary Surfactant-Associated Protein D (blood)
• Receptor for Advanced Glycation End Products (blood)
• Receptors, Tumor Necrosis Factor, Type II (blood)
• Receptors, Vascular Endothelial Growth Factor (therapeutic use)
• Recombinant Fusion Proteins (therapeutic use)
• Rectal Neoplasms (blood, drug therapy, mortality, pathology)
• Regression Analysis
• Tenascin (blood)
• Tissue Inhibitor of Metalloproteinase-1 (blood)
• Vascular Endothelial Growth Factor Receptor-1 (blood)