- •Immune checkpoint inhibitors (ICIs) may cause life-threatening adverse events (AEs).
- •The risk of cardiotoxicity of ICIs has been poorly investigated.
- •In our meta-analysis, ICIs were not associated with increased cardiotoxicity risk.
- •Cardiac AEs in clinical trials should be reported as completely as possible.
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.
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.
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.
The use of ICI as single or combination regimens is not associated with increased risk of cardiotoxicity.
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Published online: April 20, 2021
Accepted: January 29, 2021
Received in revised form: January 25, 2021
Received: November 2, 2020
© 2021 Elsevier Ltd. All rights reserved.
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- Re: Cardiotoxicity of immune checkpoint inhibitors: A systematic review and meta-analysis of randomised clinical trials: An enigmatic discordance resolvedEuropean Journal of CancerVol. 155
- PreviewImmune checkpoint inhibitors (ICIs) are revolutionary anticancer drugs approved in an expanding variety of cancer types . ICIs restore the activity of the immune system and primarily of T cells to destroy neoplastic cells . Currently, approved ICIs are monoclonal antibodies blocking cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD1), which are immune checkpoint brakes expressed on T cells . ICIs also include anti–PD-L1 (PD1 ligand located on cancer cells) normally interacting with PD1 to tone down T cells .
- Response to letter entitled: Re: Cardiotoxicity of immune checkpoint inhibitors: A systematic review and meta-analysis of randomised clinical trialsEuropean Journal of CancerVol. 155
- PreviewImmune-related myocarditis is a rare yet potentially fatal adverse event of treatment with immune-checkpoint inhibitors (ICI) [1,2]. In our systematic review and meta-analysis, we investigated the cardiotoxicity associated with ICI focusing on a broad range of cardiac adverse events (AEs), including myocarditis . As expected, since myocarditis are rare events, many trials included in the present meta-analysis did not report such events in the ICI or non-ICI arms. Overall, 16 myocarditis events (0.12%) were observed among patients receiving ICI, while only one event (0.01%) among patients not treated with ICI.