The BEVATOMOX phase II trial: raltitrexed/oxaliplatin/bevacizumab vs mFOLFOX6/bevacizumab in 2nd-line metastatic colorectal cancer

BACKGROUND: Second-line FOLFOX-bevacizumab treatment is effective in metastatic colorectal cancer (mCRC) treatment after irinotecan-based chemotherapy failure. First- or second-line raltitrexed-oxaliplatin (TOMOX) treatment has an acceptable toxicity profile in mCRC. The aim of this study was to evaluate TOMOX-bevacizumab combination as a second-line treatment. METHODS: The BEVATOMOX study was a non-comparative, prospective, randomized, open-label, multicentric phase II trial. Patients with histologically proven unresectable mCRC and progressive metastatic disease after irinotecan-based chemotherapy were randomized (1:2) to receive mFOLFOX6-bevacizumab (control arm, bevacizumab 5 mg/kg, mFOLFOX6 D1 = D15, 12 cycles) or TOMOX-bevacizumab (experimental arm, bevacizumab 7.5 mg/kg, raltitrexed 3 mg/m2 based on creatinine clearance, oxaliplatin 130 mg/m2, D1 = D21, 8 cycles). The primary endpoint was 6-month progression-free survival (6PFS). Target enrollment was 30 and 62 patients in the control and experimental arms, respectively. RESULTS: Eighty-three patients (median age 66 [48-82] years, 63.9% male, 54.2% KRAS mt) were included: 33 in the control and 50 in the experimental arms. The 6PFS rate and median overall survival were 51.5 (95% CI, 36-67) and 11.1 months (9.5-16.4) in the control arm vs 38 (95% CI, 26-51) and 9.3 (5.7-11.6) months in the experimental arm. In the experimental arm, left-sided tumors had a longer overall survival vs right-sided (11.6 vs 4.6 months, P < .001). Grade 3-4 toxicities (mucositis, neutropenia, febrile neutropenia, paresthesia, hand-foot syndrome) were similar between arms. CONCLUSION: The TOMOX-Bev combination is a feasible second-line mCRC treatment with an acceptable toxicity profile. Recruitment failure prevents efficacy conclusions, but TOMOX-Bev may be an alternative if fluropyrimidines are contraindicated. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01532804.