Tivozanib is a selective oral vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor with a long half-life and potency against all 3 VEGF receptors. Tivozanib in combination with a modified fluoropyrimidine, folinic acid, and oxaliplatin (mFOLFOX6) regimen was shown to be well-tolerated and active in patients with metastatic colorectal cancer (mCRC). BATON-CRC is a randomized, open-label, phase 2 clinical trial that compared tivozanib plus mFOLFOX6 with bevacizumab plus mFOLFOX6 in previously untreated mCRC. At ESMO 2014, Benson and colleagues presented the results of this analysis (Benson A, et al. BATON-CRC Trial. ESMO 2014: Abstract 533P). In this phase 2 trial, 265 eligible patients were randomized to receive mFOLFOX6 every 2 weeks at standard dose and scheduled with either bevacizumab 5 mg/kg every 2 weeks (n = 88) or tivozanib 1.5 mg daily (n = 177) for 21 days, followed by 7 days off treatment. A prespecified interim analysis of the BATON-CRC trial that included 95 progression-free survival (PFS) events and met prespecified futility criteria was conducted. The interim efficacy analysis showed that the median PFS (9.4 vs 10.7 months; P = .706) and the overall response rate (45.2% vs 43.2%; P = .718) were similar between the 2 treatment arms. Other efficacy parameters such as time to treatment failure and duration of response were also comparable. In terms of safety, there were more grade 3 or 4 treatment-emergent adverse events in the tivozanib arm than in the bevacizumab arm (57.1% vs 35.6%), which were mostly laboratory abnormalities such as ALT or AST elevations (16.6% vs 5.7%), and an increase in platelets (65.9% vs 43.7%). Common toxicities (all grades) included diarrhea, nausea, fatigue, neutropenia, and hypertension. Based on these preliminary results, the addition of tivozanib to mFOLFOX6 was associated with an acceptable safety profile and resulted in clinical outcomes that were comparable with those achieved with the standard bevacizumab plus chemotherapy regimen.
