Bevacizumab Plus mFOLFOX6 Versus mFOLFOX6 Alone as First-Line Treatment for RAS Mutant Unresectable Colorectal Liver-Limited Metastases: The BECOME Randomized Controlled Trial

Abstract

Purpose: To assess the effects of bevacizumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) as first-line treatment of RAS mutant unresectable colorectal liver metastases.

Methods: From October 2013 to December 2017, patients with RAS mutant unresectable liver-limited metastases from colorectal cancer were randomly assigned to receive mFOLFOX6 plus bevacizumab (arm A) or mFOLFOX6 alone (arm B). The resectability of liver metastases was determined by a local multidisciplinary team. The primary end point was the actual rate of patients converted to R0 resection for liver metastases. Secondary end points included tumor response, survival, and toxicity. The block randomization method was used.

Results: The intention-to-treat population comprised 241 patients. A total of 121 patients were randomly assigned to arm A and 120 to arm B. The median follow-up time was 37.0 months for all patients. The R0 resection rates for liver metastases were 22.3% (27 of 121 patients) in arm A and 5.8% (7 of 120 patients) in arm B, with a significant difference (P < .01). Patients in arm A had significantly better objective response rates (54.5% v 36.7%; P < .01), median progression-free survival (9.5 v 5.6 months; P < .01) and median overall survival (25.7 v 20.5 months; P = .03) compared with those in arm B. The addition of bevacizumab was associated with more frequent proteinuria (9.9% v 3.3%; P = .04) and hypertension (8.3% v 2.5%; P < .05).

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT01972490.