TOMOX-Bevacizumab Combination Shows Feasibility as Second-Line Therapy in mCRC

Key Clinical Summary:

• Design/Population: The phase 2 BEVATOMOX trial was a multicenter, randomized, open-label study comparing raltitrexed/oxaliplatin (TOMOX) plus bevacizumab versus mFOLFOX6 plus bevacizumab as second-line therapy among 83 patients with unresectable metastatic colorectal cancer (mCRC) progressing after irinotecan-based chemotherapy (median age 66 years; 54% KRAS-mutant; 66% left-sided primary).
• Key Outcomes: At a median follow-up of 30.6 months, 6-month PFS favored mFOLFOX6–bevacizumab (51.5%) over TOMOX-bevacizumab (38.0%). Median OS was 11.1 vs 9.3 months, respectively (P=0.543), and ORR was 15.2% vs 8%. In the TOMOX–bevacizumab arm, left-sided tumors had significantly longer OS than right-sided tumors (11.6 vs 4.6 months; P < 0.001).
• Clinical Relevance: TOMOX–bevacizumab demonstrated clinical feasibility and manageable toxicity comparable to standard therapy after irinotecan failure, but no overall efficacy advantage was shown. The observed tumor sidedness effect warrants further study; however, early trial discontinuation limits definitive conclusions regarding comparative efficacy.

The combination of raltitrexed and oxaliplatin (TOMOX) with bevacizumab (Bev) demonstrated clinical feasibility and manageable toxicity in patients with metastatic colorectal cancer (mCRC) progressing after irinotecan-based chemotherapy, according to results from the phase 2 BEVATOMOX trial published in The Oncologist.

Previous research has found bevacizumab combined with mFOLFOX6 to be efficacious for first- or second-line treatment of mCRC, as well as treatment with TOMOX. Researchers conducted a multicenter, randomized, open-label study to determine the safety and efficacy of bevacizumab combined with TOMOX against the standard mFOLFOX6-bevacizumab regimen as a second line treatment for mCRC among patients with unresectable, progressive mCRC.

Overall, 83 patients were included and were randomized to receive treatment with mFOLFOX6-bevacizumab (control, n = 33) or TOMOX-bevacizumab (n = 50). In the control arm, bevacizumab (5mg/kg) was administered intravenously followed by mFOLFOX6 (oxaliplatin 85 mg/m² IV infusion over 2 hours, leucovorin 200 mg/m² IV infusion over 2 hours, 5-FU bolus 400 mg/m², followed by 5-FU IV infusion 2400 mg/m² over 46 hours) on day 1 every 2 weeks (day 1 = day 15). In the experimental arm, bevacizumab (7.5mg/kg) and raltitrexed (3mg/m2) were administered intravenously according to creatinine clearance, followed by oxaliplatin 130 mg/m2 every 3 weeks (TOMOX, day 1 = day 21). 

The primary end point was 6-month progression-free survival (6PFS), with secondary assessments including overall response rate (ORR), overall survival (OS) and safety. The median age of patients was 66 years and 63.9% male, additionally, 54.2% of patients had KRAS-mutated disease. Among patients, primary tumors were left colon-sided (66.3%). 

At a median follow up of 30.6 months (95% confidence interval [CI], 18.5 to not reached), the 6PFS was higher in the mFOLFOX6-bevacizumab arm (51.5%; 90% CI, 36 to 67) compared to the TOMOX-bevacizumab arm (38.0%; 90% CI, 26 to 51) The median OS was 11.1 months (95% CI, 9.5 to 16.4) in the control arm and 9.3 months (95% CI, 5.7 to 11.6; P = 0.543) in the TOMOX-bevacizumab group. Among 79 patients evaluable for ORR, a partial response was met by 15.2% in the control arm and 8% in the TOMOX-bevacizumab arm, while 60.6% of patients in the control arm had stable disease and 58% of patients in the TOMOX-bevacizumab arm.

A significantly improved OS was found among patients with left-sided tumors in the TOMOX-bevacizumab arm compared to those with right-sided disease (11.6 vs. 4.6 months; P  < 0.001).

In terms of safety, grade 3 and 4 toxicities were comparable between the control arm and the TOMOX-bevacizumab arm, including rates of mucositis (12.1% vs 12.5%), neutropenia/febrile neutropenia (6.1 vs 8.2%), paresthesia (0% vs 6.3%), and hand-foot syndrome (3.0% vs 0%), respectively.

The researchers concluded, “Our results demonstrated the feasibility of this regimen when use after the failure of first-line irinotecan-based chemotherapy.”

They added, “However, because the trial was discontinued before reaching the target number of patients (83 instead of 92), no definitive conclusion can be drawn regarding the efficacy of the experimental treatment.”

Source:

Samalin E, Senellart H, Thezenas S, et al. The BEVATOMOX phase II trial: raltitrexed/oxaliplatin/bevacizumab vs mFOLFOX6/bevacizumab in 2nd-line metastatic colorectal cancer. The Oncologist. Published online January 14, 2026. doi:10.1093/oncolo/oyag006