Key result
ICI plus TKI therapy carries ~3.2-fold higher MACE risk versus standard therapy despite low incidence.
Why the study?
Combinations of immune checkpoint inhibitors and tyrosine kinase inhibitors can cause major adverse cardiovascular events, but the relative risk of MACEs and hypertension required systematic assessment.
Does combination therapy with immune checkpoint inhibitors and tyrosine kinase inhibitors increase the risk of MACEs and hypertension in patients with solid tumors?
Meta-Analysis (n=5,744)
Does combination therapy with immune checkpoint inhibitors and tyrosine kinase inhibitors increase the risk of MACEs and hypertension in patients with solid tumors?
Odds Ratio: 3.21 (95% CI 1.3–7.95)
Absolute Event Rate: 0.8% vs 0.2%
p-value: p=0.01
Although the addition of TKIs to ICIs significantly increases the relative risk of MACEs and hypertension, the absolute risk of MACEs remains very low (<1%), suggesting routine cardiovascular monitoring is not recommended for asymptomatic patients.
INTRODUCTION: Combinations of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) can be responsible for major adverse cardiovascular events (MACEs). We performed a meta-analysis to assess the relative risk (RR) of MACEs and hypertension in cancer patients treated with ICI+TKI combinations. RESEARCH DESIGN AND METHODS: We selected prospective trials through MEDLINE/PubMed, Cochrane Library, and ASCOMeeting abstracts. We calculated combined ORs, RRs, and 95% CIs using RevMansoftware for meta-analysis (v.5.2.3). RESULTS: = 0.11). CONCLUSIONS: ICI+TKI combinations increase the risk of MACEs compared to controls, although the absolute incidence is eventually low. Routine cardiovascular monitoring in asymptomatic patients is therefore not recommended.
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Ciccarese et al. (2024) conducted a meta-analysis in Solid tumors (n=5,744). Immune checkpoint inhibitors plus tyrosine kinase inhibitors vs. Standard therapy (VEGFR-TKIs monotherapy, single-agent ICI, or chemotherapy) was evaluated on Major adverse cardiovascular events (MACEs) of any-grade (OR 3.21, 95% CI 1.30-7.95, p=0.01). Combination therapy with immune checkpoint inhibitors and tyrosine kinase inhibitors significantly increased the risk of any-grade MACEs compared to controls (OR 3.21), although the absolute incidence was very low at 0.8%.
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