| General information |
| Database: | DB00293 |
| Objective: | Aflibercept (zivaflibercept) is an antiangiogenic agent recently approved in combination with FOLFIRI for the treatment of metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. Despite heterogeneity in response to aflibercept, no biomarkers for efficacy or adverse effects have been identified. Here they present biomarker data from the randomisedphase II AFFIRM trial assessing aflibercept in combination with mFOLFOX6 first line in mCRC. |
| Authors: | Lambrechts D, et al |
| Title: | Evaluation of efficacy and safety markers in a phase II study of metastatic colorectal cancer treated with aflibercept in the firstline setting. |
| Journal: | Br J Cancer. |
| Year: | 2015 |
| PMID: | 26355232 |
| Trial Design |
| Clinical Trial Id: | NCT00851084 |
| Agent: | aflibercept
|
| Target: | VEGFA, vascular endothelial growth factor B, PIGF
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | aflibercept+ mFOLFOX6 first line |
| Study Type: | a phase II study |
| Key Patients Feature: | metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin |
| Biomarker: | common singlenucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF) pathway genes; plasma circulating IL8 |
| Biomark Analysis: | Somatic mutations identified in KRAS, BRAF, NRAS, PIK3CA and PIK3R1 did not significantly correlate with PFS (multiple testingadjusted false discovery rate (FDR) or multiple testingadjusted FDR>0.3). |
| Control Group Info: | single arm |
| Treatment Info: | Ninetysix somatic mutations in key oncogenic drivers of mCRC and 133 common singlenucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF) pathway genes were analysed, and 27 plasma markers measured at baseline, during and after treatment. They assessed correlations of these three classes of biomarkers with progression free survival (PFS) and adverse events (AEs). |
| Primary End Point: | PFS at 12 months. |
| Secondary End Point: | the objective overall response rate, PFS, the overall survival (OS) time and safety profiling |
| Patients Number: | 236 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Somatic mutations identified in KRAS, BRAF, NRAS, PIK3CA and PIK3R1 did not significantly correlate with PFS (multiple testingadjusted false discovery rate (FDR) or multiple testingadjusted FDR>0.3). None of the individual SNPs correlated with PFS (multiple testingadjusted FDR>0.22), but at the gene level variability in VEGFB significantly correlated with PFS (multiple testingadjusted FDR=0.0423). Although none of the plasma markers measured at baseline significantly correlated with PFS, high levels of circulating IL8 at baseline together with increased levels of IL8 during treatment were significantly associated with reduced PFS (multiple testingadjusted FDR=0.0478). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | No association was found between biomarkers and AEs. |
| Conclusions: | This represents the first biomarker study in mCRC treated with aflibercept. High IL8 plasma levels at baseline and subsequent increases in IL8 they were associated with worse PFS, suggesting that IL8 may act as a potentially predictive biomarker of aflibercept treatment outcome. |