533P - BATON-CRC: A phase 2 randomized trial comparing tivozanib (tivo) + mFOLFOX6 with bevacizumab (bev) + mFOLFOX6 in stage IV metastatic colorectal can...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Colon and Rectal Cancer
Therapy
Biological Therapy
Presenter Al Benson Iii.
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors A. Benson Iii.1, J.A. Bridgewater2, I. Kiss3, F. Eskens4, J. Chen5, C. Sasse5, S. Vossen5, C. van Sant5, H. Ball5, A. Keating5, A. Krivoshik5
  • 1Northwestern University, Robert H. Lurie Comprehensive Cancer Center, 60611 - Chicago/US
  • 2Paul O'gorman Building, UCL Cancer Institute, UK WC1E 6DD - London/GB
  • 3Care Department Of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno/CZ
  • 4Dept. Of Medical Oncology, Erasmus EC Cancer Institute, NL-3015 CE - Rotterdam/NL
  • 5Global Development, Astellas Pharmaceuticals, Northbrook/US

Abstract

Aim

Tivo is a selective oral VEGF TKI with a long half-life and activity against all 3 VEGFRs. Preclinical data showed antitumor activity of tivo when added to chemotherapy (chemo). In a phase 1b study of tivo + mFOLFOX6 in mCRC and other GI cancers, partial responses were shown and the combination was well tolerated. Based on these results, a randomized, open-label, phase 2 trial of tivo + mFOLFOX6 (arm A) vs bev + mFOLFOX6 (arm B) in previously untreated mCRC was initiated.

Methods

Eligible patients had no prior systemic chemo, no fluorouracil-containing adjuvant therapy in the previous 6 mo, and an ECOG PS ≤1. No prior VEGF therapy, including bev was permitted, nor a history of significant thromboembolic or vascular disorders within 6 mo before study entry. The primary end point was PFS by investigator radiologic assessment. Secondary end points included PFS by IRR, OS, ORR, DOR, TTF, and biomarker subgroup analysis of LDH; VEGF A, C, D; CD68; myeloid-derived gene signature and serum soluble cytokines. Subjects were randomized 2:1 and stratified by LDH, origin of cancer, and number of metastatic sites, and received mFOLFOX6 q2w on days 1 and 15 of each 28-day cycle with either tivo 1.5 mg qd for 21 days followed by 7 days off treatment or bev 5 mg/kg q2w.

Results

Between 12/20/11 and 4/28/13, 265 subjects were randomized: 177 to arm A and 88 to arm B. A prespecified interim analysis included 95 PFS events and met prespecified futility criteria. mPFS (arm A vs arm B) was 9.4 mo vs 10.7 mo (P = .706); mORR: 45.2% vs 43.2% (P = .718). The overall safety profile was comparable between arms, but there were more drug-related ≥grade 3 treatment-emergent AEs in arm A (57.1% vs 35.6%), higher ALT or AST elevations >3 × ULN (16.6% vs 5.7%), and increase in grade for platelets (65.9% vs 43.7%). The most common toxicities included diarrhea, nausea, fatigue, neutropenia, and hypertension.

Conclusions

The addition of tivo to mFOLFOX6 vs bev + mFOLFOX6 met prespecified futility criteria and resulted in comparable PFS, ORR, TTF, and DOR with an acceptable safety profile. At the interim analysis, there were no significant associations between serum/tumor biomarkers and outcomes.

Disclosure

J.A. Bridgewater: • Advisory board: 2013, 1; I. Kiss: • Ad bds: Roche, Merck, Bayer • Speakers’ bureau: Roche, Merck, Amgen, Bayer, Sanofi; J. Chen, C. Sasse, S. Vossen, C. van Sant, H. Ball, A. Keating, A. Krisvoshik: Astellas employee • Stock • Salary; All other authors have declared no conflicts of interest.