Exploration of potential prognostic biomarkers in aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer. Issue 11 (21st October 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Cancer science. Volume 110:Issue 11(2019)
• Page Start: 3565
• Page End: 3572
• Publication Date: 2019-10-21
• Subjects: aflibercept -- biomarker -- colorectal cancer -- FOLFIRI -- metastasis; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14198
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : We evaluated 78 potential prognostic biomarkers of response to aflibercept plus 5‐fluorouracil/levofolinate/irinotecan treatment based on their roles in tumor progression in 62 patients with metastatic colorectal cancer. Baseline levels of eight potential biomarkers correlated with overall survival: 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.