Key result
PD-1 plus CTLA-4 inhibitor combined therapy increased the risk of grade 5 arrhythmology compared with monotherapy.
Why the study?
To evaluate the risks of cardiac adverse events in solid tumor patients treated with immune checkpoint inhibitor monotherapy or combined therapy with chemotherapy.
Do immune checkpoint inhibitors (alone or in combination) increase the risk of cardiac adverse events in patients with solid tumors compared to chemotherapy or ICI monotherapy?
Meta-Analysis (n=20,244)
Do immune checkpoint inhibitors (alone or in combination) increase the risk of cardiac adverse events in patients with solid tumors compared to chemotherapy or ICI monotherapy?
Answers are grounded in this paper and cite their sources.
Combination immune checkpoint inhibitor therapy (PD-1 plus CTLA-4) or PD-1 plus chemotherapy increases the risk of specific cardiac adverse events like arrhythmology and myocardial disease compared to monotherapy or chemotherapy alone.
BACKGROUND: We performed a systematic review and meta-analysis to evaluate the risks of cardiac adverse events in solid tumor patients treated with monotherapy of immune checkpoint inhibitors (ICIs) or combined therapy of ICIs plus chemotherapy. METHODS: Eligible studies were selected through the following databases: PubMed, Embase and clinical trials (https://clinicaltrials.gov.) and included phase III/IV randomized controlled trials (RCTs) involving patients with the solid tumor treated with ICIs. The data was analyzed by using Review Manager (version5.3), Stata (version 15.1). RESULTS: Among 2,551 studies, 25 clinical trials including 20,244 patients were qualified for the meta-analysis. Compared with PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy showed significant increase in grade 5 arrhythmology (OR 3.90, 95% CI: 1.08-14.06, p = 0.603). PD-1 inhibitor plus chemotherapy show significant increase in grades 1-5 myocardial disease (OR 5.09, 95% CI: 1.11-23.32, p = 1.000). Compared with chemotherapy, PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy show significant increase in grades 1-5 arrhythmology (OR 2.49, 95% CI: 1.30-4.78, p = 0.289). CONCLUSIONS: Our meta-analysis demonstrated that PD-1 inhibitor plus CTLA-4 inhibitor can result in a higher risk of grade 5 arrhythmology in comparison with PD-1/CTLA-4 inhibitor alone, and a higher risk of grade 5 arrhythmology in comparison with chemotherapy. PD-1 inhibitor plus chemotherapy treatment could increase the risk of all-grade myocardial disease compared with chemotherapy. However, in most cases, there was no significant increase of risks of cardiovascular toxicity in PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor plus chemotherapy compared with chemotherapy alone.
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Hu et al. (2021) conducted a meta-analysis in solid tumor (n=20,244). PD-1 inhibitor plus CTLA-4 inhibitor vs. PD-1 inhibitor or CTLA-4 inhibitor monotherapy was evaluated on grade 5 arrhythmology (OR 3.90, 95% CI 1.08-14.06, p=0.603). PD-1 plus CTLA-4 inhibitor combined therapy increased the risk of grade 5 arrhythmology compared with monotherapy.
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