From the Guidelines
Ribociclib should be discontinued if the QTc interval exceeds 500 ms or if QTc prolongation is more than 60 ms above baseline, as recommended by the European Society of Cardiology 1. When considering the management of QTc interval prolongation in patients treated with ribociclib, it's essential to prioritize the risk of torsade de pointes and other severe cardiac arrhythmias.
- The European Society of Cardiology recommends monitoring the QTc interval at baseline, 7-15 days after initiation or changes in dose, monthly during the first 3 months, and then periodically during treatment depending on the chemotherapy drug and patient status 1.
- If QTc prolongation occurs, dose interruption is recommended until the QTc returns to a safe level, and treatment can then be resumed at a reduced dose once the QTc normalizes 1.
- Patients with existing cardiac conditions, electrolyte abnormalities, or those taking other QT-prolonging medications are at higher risk for this adverse effect, and maintaining normal electrolyte levels (particularly potassium and magnesium) and avoiding other QT-prolonging medications when possible can help reduce this risk 1.
- In cases where no alternative therapy exists, the frequency of ECG monitoring of the QT interval should be increased, and the frequency of monitoring should be individualized depending on the patient’s characteristics and the causative drug 1.
From the FDA Drug Label
Permanently discontinue KISQALI if QTcF interval prolongation is either > 500 ms or > 60 ms change from baseline AND associated with any of the following: Torsades de Pointes, polymorphic ventricular tachycardia, syncope, or signs/symptoms of serious arrhythmia. If QTcF > 500 ms recurs, discontinue KISQALI.
You should discontinue ribociclib at a QTc > 500 ms that recurs, or if the QTcF interval prolongation is > 500 ms or > 60 ms change from baseline and is associated with serious arrhythmias 2.
From the Research
QTc Prolongation and Ribociclib Discontinuation
- The decision to discontinue ribociclib due to QTc prolongation should be based on the severity of the prolongation and the individual patient's risk factors for cardiac arrhythmias 3, 4, 5.
- According to the study by 3, patients with a QTc interval >450ms were initially excluded from receiving ribociclib, but when the QTc interval was recalculated using the Fridericia formula, 17 of 19 patients were able to receive the treatment without any arrhythmogenic effects.
- The study by 4 found that ribociclib was associated with a higher risk of QTc prolongation compared to other CDK4/6 inhibitors, with a relative risk of 3.12 (95% CI = 2.09 to 4.65, P < .001).
- The FDA-approved label for ribociclib recommends monitoring QTc intervals and discontinuing the drug if the QTc interval exceeds 480ms or if the patient experiences symptoms of QTc prolongation, such as syncope or arrhythmias 5.
- In general, QTc prolongation is a concern when the QTc interval exceeds 500ms, as this is associated with an increased risk of torsades de pointes and sudden cardiac death 6.
- However, the exact QTc value at which to discontinue ribociclib may vary depending on the individual patient's risk factors and medical history, and should be determined on a case-by-case basis 7.
Risk Factors for QTc Prolongation
- Patients with pre-existing cardiac conditions, such as congenital long QT syndrome or heart failure, may be at increased risk for QTc prolongation and should be monitored closely while receiving ribociclib 3, 5.
- Other risk factors for QTc prolongation include the use of other medications that can prolong the QTc interval, such as anti-arrhythmics or antipsychotics, and electrolyte disturbances, such as hypokalemia or hypomagnesemia 6.
- Patients with these risk factors should be monitored closely for signs of QTc prolongation, and the decision to discontinue ribociclib should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 4, 7.