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Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpressing malignancies, including breast and gastro-esophageal, are associated with a poor prognosis. The cardiotoxicity of trastuzumab, a HER2-targeting monoclonal antibody, is well established. However, the cardiotoxic effect of pert...

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Autores principales: Alhussein, Muhammad Mustafa, Mokbel, Abir, Cosman, Tammy, Aghel, Nazanin, Yang, Eric H., Mukherjee, Som D., Dent, Susan, Ellis, Peter M., Dhesy-Thind, Sukhbinder, Leong, Darryl P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640623/
https://www.ncbi.nlm.nih.gov/pubmed/34901806
http://dx.doi.org/10.1016/j.cjco.2021.06.019
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author Alhussein, Muhammad Mustafa
Mokbel, Abir
Cosman, Tammy
Aghel, Nazanin
Yang, Eric H.
Mukherjee, Som D.
Dent, Susan
Ellis, Peter M.
Dhesy-Thind, Sukhbinder
Leong, Darryl P.
author_facet Alhussein, Muhammad Mustafa
Mokbel, Abir
Cosman, Tammy
Aghel, Nazanin
Yang, Eric H.
Mukherjee, Som D.
Dent, Susan
Ellis, Peter M.
Dhesy-Thind, Sukhbinder
Leong, Darryl P.
author_sort Alhussein, Muhammad Mustafa
collection PubMed
description BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpressing malignancies, including breast and gastro-esophageal, are associated with a poor prognosis. The cardiotoxicity of trastuzumab, a HER2-targeting monoclonal antibody, is well established. However, the cardiotoxic effect of pertuzumab, another HER2-directed therapy, is less well documented. The objective of this systematic review and meta-analysis was to determine the risk of cardiac events in patients with HER2-positive cancer who are receiving pertuzumab. METHODS: We performed a systematic review of phase 2 and 3 randomized controlled trials in which the addition of pertuzumab to other standard therapies in patients with stage I-IV HER2-positive cancer was evaluated, and cardiac adverse effects reported. We searched MEDLINE (1946-2020), Embase (1974-2020), and CENTRAL. Two independent reviewers assessed the risk of bias and extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated from the pooled data using the inverse variance method and random-effects models. RESULTS: Eight randomized controlled trials (8420 patients) were included: 1 was gastro-esophageal; 7 were breast cancer trials. Participants’ median age ranged from 49 to 61.5 years. All participants received trastuzumab and chemotherapy in addition to pertuzumab or placebo. Compared with placebo, pertuzumab increased the risk of clinical heart failure (HF; RR [95% CI]: 1.97 [1.05-3.70]; I(2) = 0%). However, pertuzumab had no demonstrable effect on asymptomatic/minimally symptomatic left ventricular systolic dysfunction (RR [95% CI]: 1.19 [0.89-1.61]; I(2) = 19%). CONCLUSIONS: Pertuzumab increases the risk of clinical HF, but not asymptomatic/minimally symptomatic left ventricular systolic dysfunction, in HER2-positive cancer patients. Further research into the mechanisms underlying pertuzumab-related HF is needed to understand its clinical spectrum of cardiotoxicity.
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spelling pubmed-86406232021-12-09 Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis Alhussein, Muhammad Mustafa Mokbel, Abir Cosman, Tammy Aghel, Nazanin Yang, Eric H. Mukherjee, Som D. Dent, Susan Ellis, Peter M. Dhesy-Thind, Sukhbinder Leong, Darryl P. CJC Open Systematic Review/Meta-analysis BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpressing malignancies, including breast and gastro-esophageal, are associated with a poor prognosis. The cardiotoxicity of trastuzumab, a HER2-targeting monoclonal antibody, is well established. However, the cardiotoxic effect of pertuzumab, another HER2-directed therapy, is less well documented. The objective of this systematic review and meta-analysis was to determine the risk of cardiac events in patients with HER2-positive cancer who are receiving pertuzumab. METHODS: We performed a systematic review of phase 2 and 3 randomized controlled trials in which the addition of pertuzumab to other standard therapies in patients with stage I-IV HER2-positive cancer was evaluated, and cardiac adverse effects reported. We searched MEDLINE (1946-2020), Embase (1974-2020), and CENTRAL. Two independent reviewers assessed the risk of bias and extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated from the pooled data using the inverse variance method and random-effects models. RESULTS: Eight randomized controlled trials (8420 patients) were included: 1 was gastro-esophageal; 7 were breast cancer trials. Participants’ median age ranged from 49 to 61.5 years. All participants received trastuzumab and chemotherapy in addition to pertuzumab or placebo. Compared with placebo, pertuzumab increased the risk of clinical heart failure (HF; RR [95% CI]: 1.97 [1.05-3.70]; I(2) = 0%). However, pertuzumab had no demonstrable effect on asymptomatic/minimally symptomatic left ventricular systolic dysfunction (RR [95% CI]: 1.19 [0.89-1.61]; I(2) = 19%). CONCLUSIONS: Pertuzumab increases the risk of clinical HF, but not asymptomatic/minimally symptomatic left ventricular systolic dysfunction, in HER2-positive cancer patients. Further research into the mechanisms underlying pertuzumab-related HF is needed to understand its clinical spectrum of cardiotoxicity. Elsevier 2021-07-14 /pmc/articles/PMC8640623/ /pubmed/34901806 http://dx.doi.org/10.1016/j.cjco.2021.06.019 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Systematic Review/Meta-analysis
Alhussein, Muhammad Mustafa
Mokbel, Abir
Cosman, Tammy
Aghel, Nazanin
Yang, Eric H.
Mukherjee, Som D.
Dent, Susan
Ellis, Peter M.
Dhesy-Thind, Sukhbinder
Leong, Darryl P.
Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis
title Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis
title_full Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis
title_fullStr Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis
title_full_unstemmed Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis
title_short Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis
title_sort pertuzumab cardiotoxicity in patients with her2-positive cancer: a systematic review and meta-analysis
topic Systematic Review/Meta-analysis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640623/
https://www.ncbi.nlm.nih.gov/pubmed/34901806
http://dx.doi.org/10.1016/j.cjco.2021.06.019
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