1891P - The effects of glucagon-like peptide 1 agonists on immune checkpoint inhibitor-associated cardiotoxicity

Background

Immune checkpoint inhibitors (ICIs) have improved the survival outcomes of cancer but are also associated with major adverse cardiovascular events (MACE). Glucagon-like peptide 1 agonists (GLP1a) have been shown to reduce MACE in the non-cancer population; however, there is no data testing whether GLP1a reduces the risk for MACE associated with ICIs.

Methods

We conducted a retrospective, propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included all adult cancer patients with type 2 diabetes mellitus (T2DM) who were treated with an ICI. We matched patients on a GLP1a with patients on non-GLP1a diabetes medications, respectively. We excluded patients with a history of MACE to focus on the role of GLP1a in the primary prevention of MACE. The primary efficacy outcome was MACE, defined as a composite of heart failure, myocardial infarction, and myocarditis and individual components of MACE. The safety outcomes included all-cause mortality and adverse events of special interest that have been associated with the use of GLP1a.

Results

We matched 392 patients on a GLP1a with patients on non-GLP1a diabetes medications. The most common indication for an ICI was lung cancer (24%) and the most commonly used ICI was pembrolizumab (51%). In Cox proportional hazards analyses, GLP1a were associated with a lower risk of MACE (Hazard ratio (HR), 0.33 [95% CI: 0.18-0.63]) and heart failure (HR, 0.38 [95% CI: 0.18-0.79]). Patients on a GLP1a also had a lower rate of all-cause mortality than those on a non-GLP1a (HR, 0.49 [95% CI: 0.36-0.66]) without an increase in safety events. Table: 1891P

Conclusions

The use of GLP1a was associated with a reduction in MACE, heart failure, and all-cause mortality among cancer patients receiving ICIs without an increase in adverse events.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T.G.N. Neilan: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Genentech, Roivant, Roche, Sanofi, Race Oncology, C4 Therapeutics, CardiolRx, and CRC Oncology; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Abbott, and AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: National Institutes of Health/NHLBI. All other authors have declared no conflicts of interest.