Axitinib or bevacizumab (bev) plus FOLFOX or FOLFIRI as second-line therapy in patients (pts) with metastatic colorectal cancer (mCRC).

Abstract

478 Background: Axitinib (AG-013736,AG), an oral selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3, shows activity in multiple tumor types including those refractory to front-line chemotherapy. Methods: This multicenter, open-label, randomized phase II trial compared AG and bev in combination with FOLFOX or FOLFIRI in second-line mCRC. Pts previously treated with irinotecan were randomized to mFOLFOX6 plus AG 5 mg BID or bev 5 mg/kg q2wk; pts who received oxaliplatin were randomized to FOLFIRI with AG or bev at the same doses, with stratification by performance status and prior bev therapy. Primary endpoint was progression-free survival (PFS). Results: 171 pts were randomized from March 2008 to July 2009. There were no significant differences in PFS or median overall survival (mOS) between the AG and bev arms with FOLFOX or FOLFIRI. However, there was a trend towards reduced mOS in the FOLFIRI arms with AG compared to bev, and a trend towards improved mOS with AG+FOLFOX vs bev+FOLFOX. There were more treatment discontinuations (DCs) and a higher incidence of grade ≥3 adverse events (AEs) in the AG arms (diarrhea, asthenia, fatigue; Table). Conclusions: This study did not meet the primary endpoint, showing similar PFS with AG compared to bev when added to second-line chemotherapy. A potential factor in these results was earlier DCs in the AG versus bev arms, likely secondary to increased AEs. While VEGF inhibitors may have a role in second-line treatment of mCRC, at current dosing regimens AG-based chemotherapy shows no improvement in outcome compared to bev. [Table: see text] [Table: see text]