Abstract 3613
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 < 0.001), at 6-mos (-5.2%; p < 0.001) and at 12-mos (-3.7%; p = 0.004) respect to T0 in P; at 3-mos (-2.4%; p = 0.001), at 6-mos (-1.9%; p = 0.010), at 12-mos (-2.2%; p = 0.045) in R. In B and R+B patients no significant changes were observed at 3- and 12-mos, with a decrease at 6-mos (-2.5% and 3.0%, respectively; p = 0.002). Arm differences were significant (p = 0.038). GLS increased at 3-mos (5.7%; p < 0.001), at 6-mos (7.8%; p < 0.001) and at 12-mos (7.1%; p < 0.001) respect to T0 in P; at 3-mos (2.7%; p = 0.002), at 6-mos (3.2%; p = 0.014), but not at 12-mos in R; no significant changes at 3-mos, a significant increase at 6-mos (2.7%; p = 0.035), at 12-mos (3.2%; p = 0.008) in B; no significant changes at 3-, 6-, and 12-mos in R+B. Arm differences were significant (p = 0.002). Both R+B and the R arms showed a withdraw rate of 7%, with a dose reduction rates of 21% and 17%, respectively. R arm showed a significant decrease on 3D-LVEF at 12-mos as compared to T0 and will be evaluate for closure.
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.
Editorial acknowledgement
Legal entity responsible for the study
University of Florence.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4842 - The analysis of genomic signatures of head and body/tail of pancreatic cancer in Chinese patients
Presenter: Qi Ling
Session: Poster Display session 2
Resources:
Abstract
4988 - MGMT methylation in metastatic pancreatic cancer (mPAC): a single center experience
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5035 - Advantage of three-dimensional image analysis of pancreatic cancer using computed tomography
Presenter: Seung Bae Yoon
Session: Poster Display session 2
Resources:
Abstract
1465 - Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) with S-1 in patients with stage IV pancreatic cancer.
Presenter: Susumu Hijioka
Session: Poster Display session 2
Resources:
Abstract
1982 - Impact of anatomic site of biliary tract tumour origin and conditional probability of survival (CS): results from 15 prospective advanced first-line clinical trial
Presenter: Mairead McNamara
Session: Poster Display session 2
Resources:
Abstract
2244 - FOLFOXIRI versus FOLFIRINOX in first-line chemotherapy in patients with advanced pancreatic cancer: a propensity score analysis
Presenter: Angélique Vienot
Session: Poster Display session 2
Resources:
Abstract
4557 - Cellfree tumor-DNA (cfDNA) as a very early predictor of therapeutic outcome in pancreatic ductal adenocarcinoma (PDAC)
Presenter: Sabine Payr
Session: Poster Display session 2
Resources:
Abstract
4406 - Comprehensive genomic profiling (CGP) of gall bladder adenocarcinoma (GBAC) in patients from distinct ancestral populations
Presenter: Milind Javle
Session: Poster Display session 2
Resources:
Abstract
4283 - Phase II Monotherapy Efficacy of Cancer Metabolism Targeting SM-88 in Heavily Pre-Treated PDAC Patients.
Presenter: Allyson Ocean
Session: Poster Display session 2
Resources:
Abstract
2078 - Comprehensive genomic profiling and clinical outcomes in patients (pts) with fibroblast growth factor receptor rearrangement-positive (FGFR2+) cholangiocarcinoma (CCA) treated with pemigatinib in the fight-202 trial
Presenter: Antoine Hollebecque
Session: Poster Display session 2
Resources:
Abstract