Background: The combination of aflibercept to OPTIMOX (VELVET study) was evaluated in patients with previously untreated advanced colorectal cancer. A biomarker program was set-up to explore the expression of several tissue biomarkers at baseline and circulating biomarkers upon treatment cycles to identify the best monitoring biomarkers of the treatment strategy.
Methods: VELVET was a prospective, single arm phase II trial. Patient’s plasma samples were collected at baseline, and during induction therapy at day 1 of the first 6 cycles. Circulating biomarkers were analyzed using multiplexing immunoassays (31 biomarkers, 3 panels). Assays were conducted on a Biorad Bioplex platform, expect for PlGF, VEGF-A and Neuropillin-1 which were assessed using ELISA assays. Tissue biomarker were analyzed at baseline by IHC, using a BOND-Max autostainer (Leica biosystems). EGFR mutation status were analyzed using next generation sequencing.
Results: Among 49 patients included in the VELVET study from May 2013 to May 2014, 44 (90%) patients were evaluable for circulating biomarkers expression. The proportion of patients with tumor response (CR or PR) was higher in patients with high baseline levels of sVEGFR2, sEGFR, G-CSF, Prolactin and low baseline levels of VEGFA and MIF. Progression-free survival (PFS) was higher in patients with low baseline levels of Osteopontin (HR: 0.53; P=0.045) and in patients with high baseline levels of VEGF-C (HR: 0.45; P=0.014) and sVEGFR3 (HR: 0.50; P=0.045). Overall survival was higher in patients with high sVEGFR3 (HR: 0.36; P=0.030) levels. In both responders and non-responders, sVEGFR-1 and PlGF dramatically increased upon exposure to aflibercept and remained overexpressed for the all course of induction therapy. Circulation biomarkers modulations will be analyzed upon the 6 cycles. Tumor tissue biomarker assessment at baseline using IHC and theEGFR pathway mutations status will be added.
Conclusions: Exposure to aflibercept is associated with an increase of sVEGFR-1 and PlGF at cycle 1. Elevated baseline expression levels of on-target sVEGFR3 predict favorable outcome in patients treated with aflibercept.
Citation Format: Annemilai Tijeras-Raballand, Armand de Gramont, Marielle Chiron, Jean-Baptiste Bachet, Thierry Andre, Dominique Auby, Jerome Desramé, Baba-Hamed Nabil, Lecaille Cedric, Valérie Lebrun, Christophe Louvet, Annette Larsen, Christophe Tournigand, Sylvie Benner, Malika Attia, Aimery de Gramont, Franck Bonnetain, Benoist Chibaudel. Impact of circulating and tissue biomarkers in patients with metastatic colorectal cancer treated with first-line FOLFOX-aflibercept therapy. Results of the GERCOR VELVET Phase II Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2734. doi:10.1158/1538-7445.AM2017-2734
