Does Tagrisso (osimertinib) increase the risk of cardiac disease or cause hyperlipidemia in patients with non-small cell lung cancer, especially those with a history of cardiovascular disease?

Tagrisso and Cardiac Risk

Tagrisso (osimertinib) does cause cardiac disease, specifically cardiomyopathy and heart failure, but does not cause hyperlipidemia. 1

Cardiac Disease Risk with Tagrisso

The FDA label explicitly warns that Tagrisso can cause cardiomyopathy, including cardiac failure, congestive heart failure, pulmonary edema, and decreased ejection fraction, with an incidence of 3.8% in monotherapy and 9% when combined with chemotherapy. 1 Fatal cases have occurred in 0.1% of monotherapy patients and 1.1% of combination therapy patients. 1

Specific Cardiac Manifestations

• Left ventricular ejection fraction (LVEF) decline ≥10 percentage points to <50% occurs in 4.2% of patients on monotherapy and 8% of patients receiving combination therapy. 1

• QTc interval prolongation occurs in 1.1% of monotherapy patients (QTc >500 msec) and 1.8% of combination therapy patients, with 4.3% and 10.5% respectively showing increases from baseline >60 msec. 1

• Real-world data demonstrates severe cardiac adverse events (grade 3 or higher) in 4.9% of patients, including acute myocardial infarction, heart failure with reduced LVEF, and valvular heart disease. 2

• Overall cardiac abnormalities (including heart failure, atrial fibrillation, and prolonged QT) occur in approximately 19.9% of patients on osimertinib. 3

Hyperlipidemia

Tagrisso does not cause hyperlipidemia. This is not listed as an adverse effect in the FDA label 1, and hyperlipidemia is discussed in oncology guidelines only as a pre-existing cardiovascular risk factor that should be managed during cancer treatment, not as a consequence of EGFR-TKI therapy. 4

Risk Factors for Cardiac Toxicity

History of heart disease is the most significant predictor of cancer therapy-related cardiac dysfunction (CTRCD) with osimertinib (odds ratio 4.97). 5

Hypertension is the strongest independent risk factor for new-onset cardiac events with osimertinib, with a hazard ratio of 6.35 in univariate analysis and 5.36 in multivariate analysis. 3

Additional risk factors include: 2

• Pre-existing cardiovascular disease
• History of cardiovascular risk factors (hypertension, diabetes, dyslipidemia)
• Congenital long QTc syndrome 1
• Congestive heart failure 1
• Electrolyte abnormalities 1

Monitoring Requirements

Before Starting Tagrisso

For monotherapy patients: conduct cardiac monitoring including LVEF assessment at baseline only in patients with cardiac risk factors. 1

For combination therapy patients (with pemetrexed and platinum-based chemotherapy): conduct cardiac monitoring including LVEF assessment at baseline in ALL patients. 1

Obtain baseline ECG and assess electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those taking QTc-prolonging medications. 1

During Treatment

Conduct periodic ECG and electrolyte monitoring in high-risk patients (those with congenital long QTc, heart failure, electrolyte abnormalities, or on QTc-prolonging drugs). 1

Assess LVEF during treatment in patients with cardiac risk factors (monotherapy) or in all patients (combination therapy). 1

Immediately assess LVEF in any patient who develops cardiac signs or symptoms (pounding/racing heart, shortness of breath, ankle/feet swelling, dizziness, lightheadedness, or feeling faint). 1

Reversibility of Cardiac Toxicity

Osimertinib-induced cardiac dysfunction is dose-independent and reversible with drug withdrawal in most cases. 5 In one study, 6 out of 8 patients with CTRCD recovered after discontinuation, dose reduction, or switching to another EGFR-TKI. 5

LVEF typically remains low during osimertinib treatment but does not decline further, and recovery occurs with drug modification or cessation. 5

Management Algorithm

For symptomatic congestive heart failure: permanently discontinue Tagrisso. 1

For QTc interval prolongation with signs/symptoms of life-threatening arrhythmia: permanently discontinue Tagrisso. 1

For asymptomatic LVEF decline: consider dose interruption or reduction, with cardiology consultation to optimize heart failure management before potential rechallenge. 6, 5

Critical Caveats

Patients with pre-existing cardiovascular disease require thorough screening before initiating osimertinib, as these patients are at highest risk for severe cardiac events. 6, 2

The median time to cardiac events can be prolonged (median follow-up 477 days in one study), requiring sustained vigilance throughout treatment. 3

Myocardial biopsy findings in osimertinib-associated cardiomyopathy show cardiomyocyte hypertrophy and lipofuscin deposition, suggesting a distinct pathophysiology. 2

Cardiac MRI may demonstrate focal late gadolinium enhancement and myocardial edema in osimertinib-induced cardiomyopathy. 7