4839 - Bevacizumab plus chemotherapy versus chemotherapy alone as first-line treatment for patients with RAS mutant unresectable colorectal liver-limited metastases- A single center randomized control trial

Background

To assess the effects of bevacizumab plus chemotherapy as first-line treatment for RAS mutant unresectable colorectal liver metastases (CLMs).

Methods

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

Results

The intent-to-treat population comprised 241 patients. 121 patients were randomly assigned to arm A and 120 to arm B. For all patients, 35.7% (86/241) had right-sided colon cancer; 47.3% (114/241) had primary tumour resection before randomization; 86.3% (208/241) had liver metastases more than three; 33.2 (80/241) with the diameter of liver metastases more than 5 cm; 78.4% (189/241) were bilobar metastases. 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 significant difference (P < 0.01). Patients in arm A had significantly better objective response rates (54.5% v 36.7%; P < 0.01), median PFS (9.5 v 5.6 months; P < 0.01) and median OS (25.7 v 20.5 months; P = 0.03) compared with those in arm B. Addition of bevacizumab was associated with more frequent proteinuria(9.9% v 3.3%; P = 0.04) and hypertension ( 8.3% v 2.5%; P < 0.05).

Conclusions

For patients with initially unresectable RAS mutant CLMs, bevacizumab combined with chemotherapy improved the resectability of liver metastases and improved response rates and survival compared with chemotherapy alone.

Clinical trial identification

NCT01972490.

Editorial acknowledgement

Legal entity responsible for the study

Zhongshan Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.