Real-world analysis of osimertinib related cardiotoxicity - are we monitoring for this?
D M Noakes, N Letteri, D Griffin, C Bannister, A D'silvaAbstract
Background
Osimertinib is a tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer with an epidermal growth factor receptor (EGFR) mutation. It has been associated with left ventricular systolic dysfunction (LVSD), atrial fibrillation (AF) and QTc prolongation. The European Society of Cardiology (ESC) recommends performing an ECG and transthoracic echocardiogram (TTE) prior to therapy, with consideration of 3-monthly TTEs during treatment and magnesium level monitoring to mitigate the risk of QTc prolongation. Nevertheless, osimertinib remains under-recognised as a cause of cardiotoxicity, resulting in inconsistent cardiac surveillance.
Purpose
Real world data on osimertinib-related cardiotoxicity has predominantly come from East Asian populations. This study aims to assess this in a diverse European metropolitan population. Secondary aims include evaluating compliance of cardiac surveillance with the 2022 ESC Cardio-oncology guidelines.
Methods
A retrospective study of all patients treated with osimertinib at a single university hospital cancer centre between October 2023 and September 2025 was performed. Data on baseline characteristics, cardiac investigations, and outcomes was collected. Cancer therapy-related cardiovascular toxicity (CTR-CVT) was defined as per the 2022 ESC Cardio-Oncology guidelines.
Results
A total of 116 patients received osimertinib during the study period. 79 (68%) were female with a median age of 63 (IQR 56-71) years. Patients represented diverse ethnic backgrounds including 53% White, 12% Black and 8% East Asian. Compliance with ESC guidance was poor (Table 1). Before treatment only 60 (52%) patients had an ECG and 12 (10%) had a TTE performed. During treatment, 62 (53%) had an ECG, 35 (30%) had one TTE, and 13 (11%) had magnesium levels checked. Only 2 patients (2%) underwent post treatment TTE. Twelve (10%) CTR-CVT events occurred (Figure 2) of which 5% were LVSD. Of the six patients with LVSD, two had normal baseline TTEs and met criteria for cancer therapy related cardiac dysfunction (CTRCD). All had elevated NT-proBNP at diagnosis. Four (3%) were hospitalized for cardiovascular (CV) causes and two (2%) CV deaths occurred.
Conclusion
CTR-CVT events in this diverse cohort were higher than in previous studies (10%). This was likely underestimated due to limited cardiac surveillance, meaning asymptomatic CTRCD was not identified. Compliance with ESC Cardio-Oncology guidelines was low, particularly where only 10% had a baseline echocardiogram performed. These findings suggest that osimertinib may be associated with higher rates of CTR-CVT than previously thought, reinforcing the need for improved monitoring through guideline adherence. This is particularly relevant with the expanding use of osimertinib. In resource constrained healthcare systems, NT pro BNP may be useful to stratify those in need of urgent echocardiography during treatment.Table 1 Figure 1