214PPre-specified interim analysis of the SAFE trial (NCT2236806): A 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab

Abstract Background SAFE trial (NCT2236806) is a phase 3 study comparing the effect on subclinical heart damage of bisoprolol (B), ramipril (R), or both drugs (R+B), as compared to placebo (P), in breast cancer treated with (neo)adjuvant anthracyclines +/- trastuzumab. Methods Primary endpoint is subclinical cardiotoxicity measured with echocardiography and global linear strain (GLS). This interim analysis was pre-specified on the first 120 patients who had completed cardiological assessments at 12-mos. Stopping rules per arm were: dose reduction >15%, study withdraw rate >5%, and no significant impact on 3D-left ventricular ejection fraction (3D-LVEF) as compared to T0 at 12-mos assessment. Results A total of 191 out of 480 patients have been enrolled; overall 123 patients were available for the analysis (P = 34; R = 28; B = 31; R+B=30). 3D-LVEF decreased at 3-mos (-3.3%; p  Conclusions Following the stopping rules, the closure of the R arm is required and the study will continue with 3 arms. At the interim analysis, a cardioprevention strategy significantly impact on subclinical heart damage. Clinical trial identification NCT2236806. Legal entity responsible for the study University of Florence. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.