Enhancing the Anti-angiogenic Effect of Bevacizumab with ACE Inhibition on mCRC.

ABSTRACT

INTRODUCTION: Angiotensin 2 has been shown to promote angiogenesis through multiple pathways. Reduction of angiotensin 2 production by angiotensin-converting enzyme inhibitors (ACEi) could enhance the antiangiogenic effect of bevacizumab and lead to improved survival. METHODS: Data from metastatic colorectal cancer (mCRC) patients treated with bevacizumab in our hospital were retrospectively collected. Patients were divided into groups taking ACEi or angiotensin receptor blockers (ARB) or neither. We performed survival analysis and COX proportional hazard modelling and calculated the hazard ratio (HR). Multivariate analyses were performed to measure the impact of factors affecting survival, and subgroup analyses were performed for patients younger than 65 years. RESULTS: We enrolled 133 patients who received bevacizumab therapy. Eighty patients were male, and 53 were female. Twenty-three patients received ACEi treatment, and 34 patients received ARB. The median age was 58 years. Progression-free survival was higher in the ACEi group than in the ARB group or in the group receiving neither (7.66 vs. 5.98 vs. 5.0 months; p < 0.01), corresponding to a HR of 0.44 for the ACEi group (95% CI 0.26-0.74). Overall survival was not significantly longer in the ACEi group than in the ARB group or in the group receiving neither (22.0 vs. 23.5 vs. 19.7 months; p = 0.30), HR 0.66 (95% CI 0.38-1.2). In a subgroup analysis, overall survival was higher in patients younger than 65 years in the ACEi group (45.0 vs. 16.2 months; p = 0.02). CONCLUSION: In the final analysis, ACEi use in patients treated with bevacizumab resulted in prolonged progression-free survival, but this did not affect overall survival. Because our study is the first to look at the enhancement of the effect of bevacizumab by ACEi treatment and ACEi receiving patients are older, it would be useful to confirm our results by randomized trials.