Importance: Several studies have evaluated cardioprotective strategies to prevent myocardial dysfunction in patients who are receiving cardiotoxic therapies. However, the optimal approach still represents a controversial issue. Objective: To determine whether pharmacological cardioprevention could reduce subclinical heart damage in patients with breast cancer who are being treated with anthracycline-based chemotherapy. Design, Setting, and Participants: The SAFE trial was a 4-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at 8 oncology departments in Italy. It was a prespecified interim analysis on the first 174 patients who had completed cardiac assessment at 12 months. The study recruitment was conducted between July 2015 and June 2020. The interim analysis was performed in 2020. Patients were eligible for trial inclusion if they had indication to receive primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease were excluded. Interventions: Cardioprotective therapy (bisoprolol, ramipril, or both drugs compared with placebo) was administered for 1 year from the initiation of chemotherapy or until the end of trastuzumab therapy in case of ERBB2-positive patients. Doses for all groups were systematically up-titrated up to the daily target dose of bisoprolol (5 mg, once daily), ramipril (5 mg, once daily), and placebo, if tolerated. Main Outcomes and Measures: The primary end point was defined as detection of any subclinical impairment (worsening ≥10%) in myocardial function and deformation measured with standard and 3-dimensional (3D) echocardiography, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). Results: The analysis was performed on 174 women (median age, 48 years; range, 24-75 years) who had completed a cardiological assessment at 12 months and reached the end of treatment. At 12 months, 3D-LVEF worsened by 4.4% in placebo arm and 3.0%, 1.9%, 1.3% in the ramipril, bisoprolol, ramipril plus bisoprolol arms, respectively (P =.01). Global longitudinal strain worsened by 6.0% in placebo arm and 1.5% and 0.6% in the ramipril and bisoprolol arms, respectively, whereas it was unchanged (0.1% improvement) in the ramipril plus bisoprolol arm (P <.001). The number of patients showing a reduction of 10% or greater in 3D-LVEF was 8 (19%) in the placebo arm, 5 (11.5%) in the ramipril arm, 5 (11.4%) in the bisoprolol, arm and 3 (6.8%) in the ramipril plus bisoprolol arm; 15 patients (35.7%) who received placebo showed a 10% or greater worsening of GLS compared with 7 (15.9; ramipril), 6 (13.6%; bisoprolol), and 6 (13.6%; ramipril plus bisoprolol) (P =.03). Conclusions and Relevance: The interim analysis of this randomized clinical trials suggested that cardioprotective pharmacological strategies in patients who were affected by breast cancer and were receiving an anthracycline-based chemotherapy are well tolerated and seem to protect against cancer therapy-related LVEF decline and heart remodeling. Trial Registration: ClinicalTrials.gov identifier: NCT2236806.

Cardioprotective Strategy for Patients with Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial / Livi L.; Barletta G.; Martella F.; Saieva C.; Desideri I.; Bacci C.; Del Bene M.R.; Airoldi M.; Amoroso D.; Coltelli L.; Scotti V.; Becherini C.; Visani L.; Salvestrini V.; Mariotti M.; Pedani F.; Bernini M.; Sanchez L.; Orzalesi L.; Nori J.; Bianchi S.; Olivotto I.; Meattini I.. - In: JAMA ONCOLOGY. - ISSN 2374-2437. - ELETTRONICO. - 7:(2021), pp. 1544-1549. [10.1001/jamaoncol.2021.3395]

Cardioprotective Strategy for Patients with Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial

Livi L.;Desideri I.;Bacci C.;Del Bene M. R.;Scotti V.;Becherini C.;Visani L.;Salvestrini V.;Mariotti M.;Bernini M.;Sanchez L.;Orzalesi L.;Nori J.;Bianchi S.;Olivotto I.;Meattini I.
2021

Abstract

Importance: Several studies have evaluated cardioprotective strategies to prevent myocardial dysfunction in patients who are receiving cardiotoxic therapies. However, the optimal approach still represents a controversial issue. Objective: To determine whether pharmacological cardioprevention could reduce subclinical heart damage in patients with breast cancer who are being treated with anthracycline-based chemotherapy. Design, Setting, and Participants: The SAFE trial was a 4-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at 8 oncology departments in Italy. It was a prespecified interim analysis on the first 174 patients who had completed cardiac assessment at 12 months. The study recruitment was conducted between July 2015 and June 2020. The interim analysis was performed in 2020. Patients were eligible for trial inclusion if they had indication to receive primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease were excluded. Interventions: Cardioprotective therapy (bisoprolol, ramipril, or both drugs compared with placebo) was administered for 1 year from the initiation of chemotherapy or until the end of trastuzumab therapy in case of ERBB2-positive patients. Doses for all groups were systematically up-titrated up to the daily target dose of bisoprolol (5 mg, once daily), ramipril (5 mg, once daily), and placebo, if tolerated. Main Outcomes and Measures: The primary end point was defined as detection of any subclinical impairment (worsening ≥10%) in myocardial function and deformation measured with standard and 3-dimensional (3D) echocardiography, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). Results: The analysis was performed on 174 women (median age, 48 years; range, 24-75 years) who had completed a cardiological assessment at 12 months and reached the end of treatment. At 12 months, 3D-LVEF worsened by 4.4% in placebo arm and 3.0%, 1.9%, 1.3% in the ramipril, bisoprolol, ramipril plus bisoprolol arms, respectively (P =.01). Global longitudinal strain worsened by 6.0% in placebo arm and 1.5% and 0.6% in the ramipril and bisoprolol arms, respectively, whereas it was unchanged (0.1% improvement) in the ramipril plus bisoprolol arm (P <.001). The number of patients showing a reduction of 10% or greater in 3D-LVEF was 8 (19%) in the placebo arm, 5 (11.5%) in the ramipril arm, 5 (11.4%) in the bisoprolol, arm and 3 (6.8%) in the ramipril plus bisoprolol arm; 15 patients (35.7%) who received placebo showed a 10% or greater worsening of GLS compared with 7 (15.9; ramipril), 6 (13.6%; bisoprolol), and 6 (13.6%; ramipril plus bisoprolol) (P =.03). Conclusions and Relevance: The interim analysis of this randomized clinical trials suggested that cardioprotective pharmacological strategies in patients who were affected by breast cancer and were receiving an anthracycline-based chemotherapy are well tolerated and seem to protect against cancer therapy-related LVEF decline and heart remodeling. Trial Registration: ClinicalTrials.gov identifier: NCT2236806.
2021
7
1544
1549
Livi L.; Barletta G.; Martella F.; Saieva C.; Desideri I.; Bacci C.; Del Bene M.R.; Airoldi M.; Amoroso D.; Coltelli L.; Scotti V.; Becherini C.; Visani L.; Salvestrini V.; Mariotti M.; Pedani F.; Bernini M.; Sanchez L.; Orzalesi L.; Nori J.; Bianchi S.; Olivotto I.; Meattini I.
File in questo prodotto:
File Dimensione Formato  
2021 Livi et al JAMA Oncol.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: DRM non definito
Dimensione 301.5 kB
Formato Adobe PDF
301.5 kB Adobe PDF Visualizza/Apri

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1256350
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 15
social impact