Is it safe to initiate ribociclib (Ribociclib) in a patient with a prolonged QTc (QT corrected) interval of 492 milliseconds?

From the Guidelines

I would not recommend starting ribociclib with a QTc of 492ms, as it is contraindicated in patients with a baseline QTc interval greater than 450ms due to the risk of further QT interval prolongation and potentially life-threatening cardiac arrhythmias, including Torsades de Pointes, as noted in the management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations 1. Your current QTc of 492ms is already significantly prolonged beyond this safety threshold. Before considering ribociclib therapy, you would need cardiac evaluation and correction of the prolonged QTc interval. This might involve:

• Addressing electrolyte abnormalities (particularly potassium and magnesium)
• Discontinuing other QT-prolonging medications
• Treating underlying cardiac conditions. Once your QTc interval is below 450ms and stable, ribociclib could be reconsidered with regular ECG monitoring during treatment, as suggested by the cardio-oncology care in the era of the coronavirus disease 2019 (COVID-19) pandemic: an international cardio-oncology society (ICOS) statement 1. Ribociclib requires baseline ECG assessment, followed by ECG on day 14 of the first cycle, at the beginning of the second cycle, and then as clinically indicated. Alternative CDK4/6 inhibitors with less QT prolongation potential, such as palbociclib or abemaciclib, might be safer options to discuss with your oncologist in this situation, considering the risk of arrhythmia induced by psychotropic medications and the proposal for clinical management 1. It is also essential to follow the european leukemianet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia, which emphasize the importance of ECG monitoring and QT interval assessment before initiating any TKI therapy, including ribociclib 1.

From the FDA Drug Label

Cardiac Electrophysiology A concentration-QT analysis of the data in patients with breast cancer treated with KISQALI at doses ranging from 50 to 1200 mg (0. 083 to 2 times of the approved recommended high dose) suggested that ribociclib causes concentration-dependent increases in QTcF interval [see Warnings and Precautions (5.3,5.4)]. In patients with early breast cancer, the estimated mean QTcF interval change from baseline for the KISQALI 400 mg in combination with non-steroidal aromatase inhibitor (NSAI) was 10.0 ms (90% CI: 8.0,11. 9) at the mean steady-state Cmax [see Warnings and Precautions (5.3,5.4)].

The patient's QTc interval is 492ms, which is already prolonged. Given that ribociclib causes concentration-dependent increases in QTcF interval, starting ribociclib may further prolong the QTc interval, increasing the risk of cardiac arrhythmias. Therefore, it is not recommended to start ribociclib in this patient. 2

From the Research

QTc Interval and Ribociclib

• The QTc interval is a measure of the time it takes for the heart's ventricles to prepare for a new beat, and a prolonged QTc interval can increase the risk of arrhythmic events 3.
• A QTc interval of 492ms is considered prolonged, as normal QTc intervals are typically <450 ms for men and <460 ms for women 3.
• When prescribing drugs associated with QT prolongation, such as ribociclib, it is essential to consider patient-related risk factors, the potential risk and degree of QT prolongation associated with the proposed drug, and co-prescribed medicines that could increase the risk of QT prolongation 3.

Risk Factors for QTc Prolongation

• Several risk factors can contribute to QTc prolongation, including age, female sex, hypokalemia, hypocalcemia, and a history of thyroid disease or myocardial infarction 4, 5.
• The use of QT-prolonging medications, such as antiarrhythmic drugs and diuretics, can also increase the risk of QTc prolongation 4, 5.
• It is crucial to assess these risk factors when considering the initiation of ribociclib or any other medication that may prolong the QTc interval.

Monitoring and Management

• Remote monitoring of the QT interval can help promptly recognize QTc prolongation and allow for life-saving interventions or changes in drug therapy 6.
• Patch monitors recording ECG traces continuously can contribute to effective arrhythmic prevention, especially in patients with a history of QTc prolongation or those taking drugs that may prolong the QT interval 6.
• In patients with a prolonged QTc interval, such as 492ms, it is essential to carefully weigh the benefits and risks of initiating ribociclib and to closely monitor the QTc interval and adjust treatment as needed 3, 7.