BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer

摘要: Purpose: Tivozanib, a selective inhibitor of VEGFR-1, -2, and -3, plus mFOLFOX6 in an advanced gastrointestinal cancer phase Ib study had encouraging antineoplastic activity tolerable safety profile. This randomized, open-label, II trial tivozanib/mFOLFOX6 versus bevacizumab/mFOLFOX6 patients with previously untreated metastatic colorectal (mCRC) evaluated tivozanib bevacizumab. Experimental Design: Treatment-naive received every 2 weeks each 28-day cycle either orally 1.5 mg once daily for 21 days or bevacizumab intravenously 5 mg/kg weeks. Investigator-assessed progression-free survival (PFS) was the primary endpoint; some secondary endpoints included safety, overall survival, response rate (ORR), duration response, time to treatment failure, biomarker subgroup analyses. Results: A prespecified interim futility analysis demonstrated that boundary superiority over PFS intent-to-treat population crossed; median 9.4 10.7 months [HR = 1.091; confidence interval (CI), 0.693–1.718; P 0.706]. Tivozanib/mFOLFOX6 resulted ORR comparable bevacizumab/mFOLFOX6; analyses results revealed no significant association. Post hoc final potential difference tivozanib-specific low neuropilin-1 (NRP-1), but not high NRP-1. adverse events were both previous studies. Conclusions: The efficacy superior mCRC. Since data from did demonstrate superiority, this discontinuation study. tolerability profile consistent other trials. NRP-1 is predictive activity, these require further validation. Clin Cancer Res; 22(20); 5058–67. ©2016 AACR.