Osimertinib linked to cardiac events in NSCLC patients

Patients with non-small cell lung cancer (NSCLC) treated with osimertinib have a higher risk of QT prolongation, reduced ejection fraction, and high-grade cardiac failure than those who received placebo or other standard therapies, reports a study.

This finding highlights “the need for careful cardiac monitoring for early recognition and intervention to improve quality of life and clinical outcomes,” said lead study author Dr Zin Win, UC Riverside, Riverside, California, US. [AHA 2025, abstract 4367292]

Zin and colleagues performed a meta-analysis to assess the incidence and relative risk of cardiac adverse events in NSCLC patients treated with osimertinib. They did a comprehensive literature search using the databases of Medline and Embase from inception through 31 May 2025 and included phase III randomized controlled trials (RCTs) that reported cardiac adverse events in patients using osimertinib.

The estimated pooled risk ratio (RR) with 95 percent confidence intervals (CIs) was calculated using the Mantel-Haenszel method. A random effects model was also applied.

Six phase III RCTs (MARIPOSA: n=849; LAURA: n:216; AURA3: n=415; FLAURA: n=556; ADAURA: n=680; NCT02959749: n=147) involving a total of 2,863 patients were included in the analysis.

Significantly more patients receiving osimertinib experienced QT prolongation of any grade than those in control arms (4.83 percent vs 1.50 percent; RR, 3.32, 95 percent CI, 2.06‒5.34; p<0.00001). Moreover, high-grade QT prolongation occurred in 1.24 percent of patients in the osimertinib arm compared with only 0.30 percent of controls (RR, 3.25, 95 percent CI, 1.16‒9.12; p=0.02).

Ejection fraction

Similarly, more cases of decreased ejection fraction of any grade were recorded in the osimertinib arm than the control arm (2.35 percent vs 1.05 percent; RR, 2.25, 95 percent CI, 1.23‒4.11; p=0.008). The same trend was observed in the incidence of high-grade cardiac failure (1.70 percent with osimertinib vs 0.53 percent with control; RR, 3.02, 95 percent CI, 1.32‒6.95; p=0.009).

On the other hand, no statistically significant between-group difference was noted in the incidence of high-grade decreased ejection fraction (0.85 percent vs 0.15 percent; RR, 3.40, 95 percent Ci, 0.95‒12.15; p=0.06) and high-grade pericardial effusion (0.33 percent vs 0.38 percent; RR, 1.01, 95 percent CI, 0.31‒3.28; p=0.98).

These findings supported those of another meta-analysis, which included 2,518 patients receiving osimertinib monotherapy in the single-arm analysis and 1,815 participants in the comparative analysis.

This study demonstrated the association of osimertinib with an increased risk of heart failure, arrhythmias, and left ventricular ejection fraction decline. Such associations call for “proactive cardiac monitoring for patients, especially those with existing cardiovascular risk factors.” [AHA 2025, abstract 4366513]

“Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is crucial in the treatment of EGFR-mutant NSCLC. It exerts its effect by selectively binding to mutant EGFR and inhibiting downstream signalling pathways involved in cell proliferation and survival,” Win said.

“However, emerging evidence has raised concerns about its potential cardiovascular toxicity,” Win added.