The BEVATOMOX phase II trial: raltitrexed/oxaliplatin/bevacizumab vs mFOLFOX6/bevacizumab in 2nd-line metastatic colorectal cancer
Mené sur 83 patients atteints d'un cancer colorectal de stade métastatique (âge médian : 66 ans), cet essai de phase II compare l'efficacité, du point de vue de la survie sans progression à 6 mois, et la toxicité de deux traitements de deuxième ligne utilisés en combinaison avec le bévacizumab, l'un de type mFOLFOX6 et l'autre de type TOMOX (raltitrexed/oxaliplatine)
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 study was to evaluated 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 six-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 < 0.001). 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.
The Oncologist , résumé, 2026