Addition of Bevacizumab to mFOLFOX6 for the First-Line Treatment of RAS-Mutant Unresectable Colorectal Liver Metastases

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In a Chinese single-institution trial reported in the Journal of Clinical Oncology, Tang et al found that the addition of first-line bevacizumab to mFOLFOX6 (modified fluorouracil, leucovorin, and oxaliplatin) resulted in a higher rate of conversion to R0 resection in patients with RAS-mutant, initially unresectable colorectal cancer liver metastases. 

Study Details

In the BECOME trial, 241 patients (intent-to-treat population) enrolled at Zhongshan Hospital, Shanghai, were randomly assigned between October 2013 and December 2017 to receive bevacizumab (5 mg/kg every 2 weeks) plus mFOLFOX (n = 121) or mFOLFOX alone (n = 120). Resectability of liver metastases was determined by a local multidisciplinary team. The primary endpoint was rate of patients converted to R0 resection for liver metastases.

Treatment Outcomes


  • The addition of bevacizumab to mFOLFOX improved the rate of conversion to R0 resection.
  • The bevacizumab group had improved response rate and progression-free and overall survival.

Median follow-up was 37.0 months. R0 resection was achieved in 27 patients (22.3%) in the bevacizumab group vs 7 patients (5.8%) in the control group (P < .01).

Objective response was achieved in 66 patients (54.5%; 1 complete response) in the bevacizumab group vs 44 patients (36.7%; 1 complete response) in the control group (P < .01). An additional 31.4% vs 28.3% of patients had stable disease.

Median progression-free survival was 9.5 vs 5.6 months (hazard ratio [HR] = 0.49, P < .001). Median overall survival was 25.7 vs 20.5 months (HR = 0.71, P = .03), with 1-, 2-, and 3-year rates of 94.1% vs 75.6%, 53.0% vs 40.4%, and 26.5% vs 20.5%.

Adverse Events

Grade 3 or 4 adverse events occurred in 39.7% of the bevacizumab group vs 26.7% of the control group (P = .032), with the most common in both groups being leukopenia/neutropenia (14.1% vs 12.5%). The bevacizumab group had a higher incidence of grade 3/4 proteinuria (9.9% vs 3.3%, P = .040) and hypertension (8.3% vs 2.5%, P = .048). Hemorrhage occurred in 3.3% vs 1.7% and thrombosis in 3.3% vs 0%. Adverse events led to treatment discontinuation in 12.4% vs 10.8% of patients. No grade 5 adverse events were reported.

The investigators concluded, “For patients with initially unresectable RAS-mutant colorectal liver metastases, bevacizumab combined with mFOLFOX6 increased the resectability of liver metastases and improved response rates and survival compared with mFOLFOX6 alone.”

Jianmin Xu, MD, PhD, of the Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Natural Science Foundation of China, Clinical Science and Technology Innovation Project of Shanghai, and others. For full disclosures of the study authors, visit

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