The VELOUR study (Van Cutsem, et al. 2012) showed that the addition of aflibercept to irinotecan-based chemotherapy (FOLFIRI) in patients with metastatic colorectal cancer (mCRC) refractory to oxaliplatin-based chemotherapy was associated with improved progression-free and overall survival. IL-8 enhances cell proliferation and survival and promotes tumor angiogenesis (Lee, et al. 2012). In the randomized phase II AFFIRM study, conducted in mCRC patients treated with oxaliplatin-based chemotherapy with or without aflibercept, high serum levels of circulating IL-8 were significantly associated with reduced PFS (Lambrechts, et al. 2015). While in patients treated without aflibercept, PFS was independent on IL-8 levels, patients treated with aflibercept with IL-8 levels ≤ vs. > 19 pg ml−1 presented a median progression free survival of 9.3 (7.52–11.10) vs. 4.1 (2.33–8.54) months. The FLIBER trial aims to explore the predictive value of serum levels of IL-8 and other cytokines in a population of mCRC patients receiving aflibercept plus FOLFIRI.
The FLIBER trial is a phase IV single arm study which plans to enroll 124 patients with mCRC resistant to or progressed after an oxaliplatin-containing regimen who are planned to start aflibercept in combination with FOLFIRI as per standard clinical practice and decision by their treating oncologist. Patients will be assessed for a serum cytokine panel at baseline, after 2 months of treatment and at radiologic progression. The primary end point is progression free survival (PFS), with the objective to estimate the difference in PFS between the two groups defined on the basis of their baseline IL-8 levels ( > = vs. < than median). The secondary endpoints are Radiologic Response Rate (rRR), Overall Survival (OS) and Safety profile and their relationship with IL-8 levels and the other cytokines assessed. Assessed cytokines include PDGF, IL-1b, IP10, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, bFGF, GCSF, GMCSF, IFNg, MCP1, MIP1a, MIP1b, RANTES, TNFa and VEGF, VEGFA, T-cad, VEGFR3, SAP, VDBP, neuropilin1, CRP, endoglin, PlGF.
Clinical trial identification
Legal entity responsible for the study
Fondazione Ricerca Traslazionale (FoRT).
C. Buonerba: Research support to Institution, Consultancy. All other authors have declared no conflicts of interest.