LAUSR

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, ICIs have been linked to serious immune-related cardiovascular adverse events. Pembrolizumab has recently been approved for breast cancer treatment, but data on its impact on immune-related cardiovascular adverse events are limited. We aimed to investigate the incidence and risk of cardiovascular events associated with pembrolizumab use in breast cancer patients. Methods: We conducted a retrospective, propensity score-matched cohort study using the TriNetX Analytics Network database, which includes de-identified electronic health records from over 70 healthcare organizations and 101 million individuals. We included adult female breast cancer patients treated with pembrolizumab from November 2020 to May 2023. Patients who received endocrine or HER2-targeted therapies were excluded. We compared patients who received pembrolizumab and chemotherapy with those who received chemotherapy alone. The primary outcome was major adverse cardiovascular events (MACE), including myocarditis, pericarditis, myocardial infarction, heart failure, ischemic stroke, and cardiac arrest. Secondary outcomes included individual MACE components and other cardiovascular events such as atrial fibrillation and conduction disorders. All outcomes were captured within one year following the start of ICI therapy. Results: We identified 9,913 eligible patients, of whom 1,834 received pembrolizumab and chemotherapy, and 8,079 received chemotherapy alone. After propensity score matching, 1,294 patients in each cohort were well balanced for demographics, cancer therapy, comorbidities, and cardiovascular medication use. The mean age for the pembrolizumab-chemotherapy and chemotherapy-only cohorts were 54.7 ± 13.4 and 54.7 ± 13.2 years, respectively. The background prevalence for hypertension (24.4% vs 23.8%) and hyperlipidemia (19.3% vs 18.0%) were similar between the two groups. Both groups received similar cancer treatments, including mastectomy (5.0% vs. 5.3%), radiation treatment (6.3% vs. 6.2%), taxanes (73.6% vs. 72.5%), platinum compounds (70.4% vs. 69.7%), anthracyclines (22.2% vs. 23.7%), and cyclophosphamide (21.6% vs. 23.2%). Over a median follow-up of 12 months, the incidence of MACE was higher in the pembrolizumab-chemotherapy cohort (9.9 events per 100 patient-years) compared to the chemotherapy-only cohort (4.5 events per 100 patient-years). The pembrolizumab-chemotherapy cohort had an approximately 2.2-fold higher risk of MACE (Hazard ratio (HR), 2.18 [95% CI: 1.60-2.98]). There were five cases of myocarditis in the pembrolizumab-chemotherapy cohort, while no cases were detected in the chemotherapy-only cohort. Furthermore, pembrolizumab was associated with a significantly increased risk of heart failure (HR, 3.58 [95% CI: 1.89-6.78]), atrial fibrillation/flutter (HR, 3.78 [95% CI: 1.82-7.87]), conduction disorders (HR, 2.81 [95% CI: 1.37-5.76]), and cardiac arrest (HR, 4.80 [95% CI: 1.05-21.90]). Patients on pembrolizumab also showed a higher tendency to develop pericarditis (HR, 1.80 [95% CI: 0.96-3.37]) and myocardial infarction (HR, 1.64 [95% CI: 0.75-3.58]). Conclusion: The use of pembrolizumab is associated with more than a two-fold increased risk of MACE among breast cancer patients. Further studies are needed to optimize the detection and management of ICI-associated cardiovascular events in this population. Citation Format: Cho-Han Chiang, Xiaocao “Haze” Xu, Junmin Song, Nutchapon Xanthavanij, Kuan-Yu Chi, Yu-Cheng Chang, Yu Chang, Chieh-Lien Hsiao, Yuan Ping Hsia, Cho-Hung Chiang, Shuwen Lin. The incidence and risk of cardiovascular events associated with pembrolizumab in patients with breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS5-02.