Elisa Agostinetto1, Daniel Eiger2, Matteo Lambertini3, Marcello Ceppi4, Marco Bruzzone4, Noam Pondé5, Chris Plummer6, Ahmad H Awada7, Armando Santoro8, Martine Piccart-Gebhart7, Evandro de Azambuja2. 1. Academic Trials Promoting Team, Institut Jules Bordet, L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium; Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center - IRCCS, Humanitas Cancer Center, via Manzoni 56, 20089, Rozzano, Milan, Italy; Humanitas University, Department of Biomedical Sciences, via Rita Levi Montalcini 4, 20090 Pieve Emanuele - Milan, Italy. Electronic address: elisa.agostinetto@bordet.be. 2. Academic Trials Promoting Team, Institut Jules Bordet, L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium. 3. Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. 4. Unit of Clinical Epidemiology, IRCCS Ospedale Policlinico San Martino, Genova, Italy. 5. Clinical Oncology Department, AC Camargo Cancer Center, São Paulo, Brazil. 6. Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK. 7. Oncology Department, Institut Jules Bordet, Brussels, Belgium. 8. Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center - IRCCS, Humanitas Cancer Center, via Manzoni 56, 20089, Rozzano, Milan, Italy; Humanitas University, Department of Biomedical Sciences, via Rita Levi Montalcini 4, 20090 Pieve Emanuele - Milan, Italy.
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) may cause potentially life-threatening adverse events (AEs), but the risk of cardiotoxicity has not been fully investigated. It is also unknown whether ICI combinations increase cardiotoxicity compared with single ICI. We aimed to assess the cardiotoxicity of ICI in a range of tumour types. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines (PROSPERO registration number: CRD42020183524). A systematic search of PubMed, MEDLINE, Embase databases, and conference proceedings was performed up to 30 June 2020. All randomised clinical trials comparing ICI with other treatments (primary objective) or dual-agent ICI versus single-agent ICI (secondary objective) in any solid tumour were included. Pooled risk ratios (RRs) with 95% confidence intervals (95% CIs) for cardiotoxicity events were calculated using random effect models. RESULTS: Eighty studies including 35,337 patients were included in the analysis (66 studies with 34,664 patients for the primary endpoint and 14 studies with 673 patients for the secondary endpoint). No significant differences in terms of cardiac AEs were observed between ICI and non-ICI groups (RR 1.14, 95% CI 0.88-1.48, p = 0.326) nor between dual ICI and single ICI groups (RR 1.91, 95% CI 0.52-7.01, p = 0.329). Myocarditis incidence did not significantly differ between ICI and non-ICI groups (RR 1.11, 95% CI 0.64-1.92, p = 0.701) nor between dual ICI and single ICI groups (RR 1.10, 95% CI 0.31-3.87, p = 0.881). No differences were observed in subgroup analyses according to tumour type, setting of disease, treatment line, and type of treatment. CONCLUSION: The use of ICI as single or combination regimens is not associated with increased risk of cardiotoxicity.
BACKGROUND: Immune checkpoint inhibitors (ICIs) may cause potentially life-threatening adverse events (AEs), but the risk of cardiotoxicity has not been fully investigated. It is also unknown whether ICI combinations increase cardiotoxicity compared with single ICI. We aimed to assess the cardiotoxicity of ICI in a range of tumour types. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines (PROSPERO registration number: CRD42020183524). A systematic search of PubMed, MEDLINE, Embase databases, and conference proceedings was performed up to 30 June 2020. All randomised clinical trials comparing ICI with other treatments (primary objective) or dual-agent ICI versus single-agent ICI (secondary objective) in any solid tumour were included. Pooled risk ratios (RRs) with 95% confidence intervals (95% CIs) for cardiotoxicity events were calculated using random effect models. RESULTS: Eighty studies including 35,337 patients were included in the analysis (66 studies with 34,664 patients for the primary endpoint and 14 studies with 673 patients for the secondary endpoint). No significant differences in terms of cardiac AEs were observed between ICI and non-ICI groups (RR 1.14, 95% CI 0.88-1.48, p = 0.326) nor between dual ICI and single ICI groups (RR 1.91, 95% CI 0.52-7.01, p = 0.329). Myocarditis incidence did not significantly differ between ICI and non-ICI groups (RR 1.11, 95% CI 0.64-1.92, p = 0.701) nor between dual ICI and single ICI groups (RR 1.10, 95% CI 0.31-3.87, p = 0.881). No differences were observed in subgroup analyses according to tumour type, setting of disease, treatment line, and type of treatment. CONCLUSION: The use of ICI as single or combination regimens is not associated with increased risk of cardiotoxicity.
Authors: Vincenzo Quagliariello; Margherita Passariello; Annabella Di Mauro; Ciro Cipullo; Andrea Paccone; Antonio Barbieri; Giuseppe Palma; Antonio Luciano; Simona Buccolo; Irma Bisceglia; Maria Laura Canale; Giuseppina Gallucci; Alessandro Inno; Claudia De Lorenzo; Nicola Maurea Journal: Front Cardiovasc Med Date: 2022-09-08