Exploratory evaluation of pharmacodynamic biomarkers and pharmacokinetics (PK) of ziv-aflibercept (Z) + FOLFIRI in a phase II study of Japanese patients (pts) with metastatic colorectal cancer (mCRC).

799 Background: Z + 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) is a 2 nd -line treatment for mCRC. There are no established biomarkers that predict response to this treatment. This study aimed to identify such biomarkers. Methods: 62 pts with mCRC received Z (4 mg/kg) + FOLFIRI every 2 weeks. 78 potential protein biomarkers (e.g., cytokines) were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor-stroma interaction. Plasma levels of biomarkers at baseline and pre-dose 3 (Day 1 of Cycle 3) were measured in all pts by enzyme-linked immunosorbent assays. Relationships between these levels and efficacy endpoints were assessed. PK data were calculated. Results: 10 potential biomarkers had a ±30% change from baseline to pre-dose 3 (adjusted P < .001); the greatest changes were in placental growth factor (median: 4,716%) and vascular endothelial growth factor receptor 1 (2,171%). Baseline levels of 8 potential biomarkers correlated with overall survival (OS; see table) in a univariate Cox regression analysis; none correlated with progression-free survival or maximum tumor shrinkage. Pre-dose 3 levels did not correlate with any efficacy endpoints. Conclusions: Preliminary data show that these 8 biomarkers could be associated with OS. No significant drug interactions were found. Clinical trial information: NCT01882868. [Table: see text]