2713 - Cardiac Events and Dynamic Echocardiogram Changes in Low Cardiovascular Risk Patients with Triple Negative Breast Cancer Treated with Immunotherapy

J. P. Nesseler¹, K. Silos¹, O. Peony¹, A. Singh¹, P. Belen¹, M. Seok², J. Steers¹, M. Kamrava¹, A. J. Mirhadi¹, M. Burnison¹, J. K. Jang¹, S. L. Shiao¹, R. H. Mak³, A. Nikolova⁴, and K. M. Atkins¹; ¹Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, ²Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, ³Department of Radiation Oncology, Brigham and Womens Hospital/Dana-Farber Cancer Institute, Boston, MA, ⁴Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA

Purpose/Objective(s): While increased cardiovascular (CV) toxicity has been observed with chemotherapy, immunotherapy, and radiotherapy (RT), the cumulative CV risk in the setting of novel multi-modality treatment regimens remains incompletely understood. Our objective was to characterize early CV toxicity in patients with triple negative breast cancer (TNBC) treated with immunotherapy. Materials/

Methods: Retrospective analysis of 85 women with early TNBC treated from 2018-2024 with chemotherapy-pembrolizumab (chemo-IO) and =1 transthoracic echocardiogram (TTE). Coronary artery calcium (CAC) was measured from baseline CT scans. Grade =2 cardiac common terminology criteria for adverse events (CTCAE) cumulative incidence estimates and Fine and Gray regressions (non-cardiac death as competing risk) were calculated. TTE and electrocardiogram (ECG) parameters from during vs after systemic therapy (vs baseline) were compared using descriptive statistics.
Results: The median age was 50 years (interquartile range [IQR] 38-61), 19% had hypertension, 17% hyperlipidemia, and 0% known cardiovascular disease. Most (97%) received neoadjuvant chemo-IO, 79% received RT (53% breast/chest wall only; 47% included regional nodes; 8% intensity-modulated RT; 82% with boost; 69% standard fractionation, 81% deep inspiration breath-hold; median mean heart and left anterior descending [LAD] coronary artery doses of 1.5 Gy and 3.0 Gy, respectively). 82% had baseline CAC of 0, while only 4% had CAC >100. The median follow up was 19 months (IQR, 14-39). The 1-year cumulative incidence of grade =2 cardiac CTACE was 9.6% with a median time to event of 16 months (IQR 13-34). Most (7/9) were grade 2 (n=5 ejection fraction [EF] decline, n=1 heart failure, n=1 pericarditis); n=2 were grade =3 (myocarditis, urgent percutaneous coronary intervention). Among those treated with RT and dose plans available (n=53), adjusting for age and CAC score, mean LAD dose was associated with an increased risk of cardiac events (adjusted hazard ratio [aHR] 1.16/Gy, 95% confidence interval [CI] 1.01-1.35; p=.041). Of n=30 with TTE at a median 23 months post chemo-IO start, there was an increased frequency of moderate diastolic dysfunction vs baseline (13% vs 2%, respectively; p=.013). Among the 5 patients with grade 2 EF decline, 3/5 ultimately had recovery in EF, though 2/5 did not have further evaluation. On ECG evaluation, there was increased frequency of QTc prolongation >450 ms on post-treatment ECG vs baseline (39% vs 15%; p=.031).
Conclusion: Early CV toxicity related to chemo-IO based TNBC treatment (including RT) was observed, even in young patients with low CV risk profiles, highlighting the importance of early CV surveillance. Longer follow-up is warranted to identify moderate- or late-term cardiac changes, as later effects of treatment (i.e., LAD radiation exposure) may not yet be fully accounted for.