The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer.

3533 Background: Circulating angiogenic factors have been previously shown to be altered in patients (pts) with mCRC on bevacizumab (BV)-containing regimens. However, a systematic evaluation of alterations in levels of the VEGF family of ligands may provide insights into resistance mechanisms. Methods: 42 patients (pts) with mCRC were treated on a single arm phase II study with 5-FU, irinotecan, and BV (FOLFIRI+BV), and plasma was collected for cytokine levels. VEGF-C, VEGF-D, and PlGF were measured using ELISA (R&D) or suspension bead multiplex assay (BioRad). Plasma samples were obtained at baseline, prior to radiographic progression, and at the time of radiographic progression. In a retrospective larger cohort used for validation, plasma from 403 matched pts with mCRC were obtained prior to any chemotherapy or after progression on a regimen with or without bevacizumab. Comparisons were done by the two-sided, nonparametric Wilcoxon paired test. Results: Following FOLFIRI+BV treatment, VEGF-C was increas...