Cardiac adverse events of PD-1 and PD-L1 inhibitors in cancer protocol for a systematic review and network meta-analysis

Abstract

Introduction: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in the treatment of cancer. Immunosuppressive therapy can control the cancer well and is suitable for the moderate to severe diseases. However, according to clinical observation, immune-related cardiac adverse events against PD-1or/and PD-L1 are inevitable, but generally reversible. Understanding the cardiac adverse events of PD-1 or/and PD-L1 inhibitors is crucial to improve the anti-cancer efficacy and ensure the life safety of patients. The variability of cardiac adverse events between different immunosuppressants and different cancers is not clear. Methods and analysis: This protocol established in this study has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search the following electronic bibliographic databases: PubMed, Cochrane Library, EMBASE databases and ClinicalTrials.gov from their inception to December 2019. We will use a combination of Medical Subject Heading, and free-text terms with various synonyms to search based on the Eligibility criteria. We will include RCTs on PD-1 or/and PD-L1 inhibitors therapy to analyze. In addition, our study will include some clinical trials. All relevant RCTs will be included, such as early phase I/II, phase III experimental trials, prospective and retrospective observational studies. According to the inclusion and exclusion criteria outlined above, the full texts of each eligible study will be retrieved for further identification by one reviewer. Two authors will screen the titles and abstracts of all records retrieved in above electronic databases independently to find potentially eligible reviews. Data will be extracted by 2 reviewers independently using a pre-designed data extraction form. The other reviewer will validate data. I-square (I2) test, substantial heterogeneity, sensitivity analysis and publication bias assessment will be performed accordingly. For our network meta-analysis, we will use Stata 15.0 and WinBUGS 1.4.3. Ethics and dissemination: Ethics approval and patient consent would be not required because the data of this network meta-analysis mainly are obtained from existing resources. This network meta-analysis will be published in a peer-reviewed journal. PROSPERO number: CRD42019142865

Cardiotoxicity associated with immune checkpoint inhibitors: Current status and future challenges

“…Some of these complications can develop and progress rapidly within a few days or weeks after ICI treatment. However, several complications, such as chronic diseases, can increase the risk of cardiovascular disease-associated morbidity and mortality in the long term ( Han et al, 2020 ).…”

“…Therefore, combination medication is the clearest risk factor for ICI-related myocarditis, and combined conduction diseases have the highest mortality rate ( Varricchi et al, 2017a ; Chen et al, 2018 ). Immune-mediated myocarditis is characterized by fulminant progression ( Han et al, 2020 ), and the early stage of combination medication, especially the first course of treatment, is considered a high-risk period that causes explosive myocardial damage and death. Although combination drugs have a stronger anti-tumor effect than single drugs, they are double-edged swords, and a trade-off is often faced when using combination therapy.…”