From the Guidelines
Osimertinib should be held if the QTc interval exceeds 500 milliseconds or increases by more than 60 milliseconds from baseline. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of monitoring QTc intervals in patients receiving osimertinib, a tyrosine kinase inhibitor used for non-small cell lung cancer 1. The study suggests that treatment should be temporarily interrupted if the QTc is ≥500 ms (or QTc prolongation is ≥60 ms above baseline), and electrolyte abnormalities corrected and cardiac risk factors for QT prolongation controlled before resuming treatment at a reduced dose. Regular electrocardiogram monitoring is recommended for patients with risk factors for QT prolongation, including electrolyte abnormalities, congenital long QT syndrome, or concurrent use of medications known to prolong the QT interval. Patients should also be educated about symptoms of arrhythmias such as palpitations, dizziness, or syncope, which should prompt immediate medical attention.
Key considerations for managing QTc prolongation in patients receiving osimertinib include:
- Correcting predisposing factors such as concomitant electrolyte abnormalities or QT-prolonging drugs
- Temporarily interrupting treatment if QTc is ≥500 ms or QTc prolongation is ≥60 ms above baseline
- Resuming treatment at a reduced dose once the QTc normalizes
- Increasing the frequency of ECG monitoring of the QT interval if no alternative therapy exists
- Individualizing the frequency of monitoring based on the patient’s characteristics and the causative drug.
It is essential to weigh the benefits of osimertinib treatment against the risk of torsade de pointes, particularly in patients with substantial morbidity and mortality associated with malignancy 1. By prioritizing QTc interval monitoring and management, healthcare providers can minimize the risk of potentially life-threatening ventricular arrhythmias and optimize patient outcomes.
From the FDA Drug Label
QTc interval greater than 500 msec on at least 2 separate ECGs‡ Withhold TAGRISSO until QTc interval is less than 481 msec or recovery to baseline if baseline QTc is greater than or equal to 481 msec, then resume at 40 mg dose.
Osimertinib needs to be held when the QTc interval is greater than 500 msec on at least 2 separate ECGs. It should be withheld until the QTc interval is less than 481 msec or recovery to baseline if the baseline QTc is greater than or equal to 481 msec, then resumed at a 40 mg dose 2.
From the Research
Osimertinib and QTc Interval
- The studies 3, 4, 5, 6, 7 discuss the relationship between osimertinib and QTc interval prolongation, but do not provide a specific QTc value at which osimertinib needs to be held.
- However, the studies suggest that osimertinib can cause QTc interval prolongation, which can lead to ventricular arrhythmias and torsade de pointes 3, 4, 5, 6.
- The management of QTc interval prolongation in patients taking osimertinib is crucial, and discontinuation of the drug may be necessary in some cases 4, 6, 7.
- It is recommended to monitor patients taking osimertinib for QTc interval prolongation, especially those with risk factors for cardiotoxicity 6, 7.
- The studies do not provide a clear consensus on the specific QTc value at which osimertinib needs to be held, and the decision to discontinue the drug should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history.