High incidence and reversible bradycardia events following alectinib initiation

Abstract

Background With the widespread use of alectinib in patients with anaplastic lymphoma kinase (ALK)‐positive non‐small‐cell lung cancer (NSCLC), its cardiotoxicity has gradually emerged, including new‐onset sinus bradycardia (SB). However, the incidence, timing, severity, and risk factors of alectinib‐induced bradycardia remain unknown. Methods From January 2020 to June 2022, 93 patients with ALK‐positive NSCLC treated with alectinib were enrolled in this retrospective analysis. These patients had heart rate (HR) recorded before and after alectinib administration. By reviewing electronic medical records and follow‐up, the HR changes of patients during medication were recorded. The potential risk factors associated with alectinib‐induced SB were explored. Results According to an HR cut‐off of 60 beats per minute (bpm), 47 patients (50.54%) experienced at least one recorded bradycardia. The mean HR of total participants before alectinib administration was 78.32 (standard deviation [SD], 9.48) and after was 64.88 (SD, 12.21). The median maximum change in HR (range) for all patients was 11 (−55, +4) bpm. For the bradycardia subgroup, the HR of most patients (76.60%) hovered around 50–60 bpm, and 61.70% of SB occurred within 3 months after alectinib administration. Multivariate analysis indicated that baseline HR (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.79–0.93, p < 0.001) and history of hypertension (OR 13.71, 95% CI 2.49–76.38, p = 0.003) were independent risk factors for alectinib‐related bradycardia. Conclusions Alectinib‐induced bradycardia had a high incidence, appeared relatively early, and was reversible by dose reduction or withdrawal.

Cardiac Arrhythmias in Oncological Patients—Epidemiology, Risk Factors, and Management within the Context of the New ESC 2022 Guidelines

“…Another group of medicines associated with an increased risk of developing bradycardia is ALK inhibitors, such as crizotinib, ceritinib, or alecitinib widely used in the treatment of NSCLC. A retrospective analysis was made to assess the risk of sinus bradycardia in patients treated with alecitinib [ 37 ]. Between the years 2020 and 2022, 93 patients with ALK-positive NSCLC diagnosis and who were treated with alecitinib were analyzed.…”

Predictors of bradycardia in non-small-cell lung cancer patients receiving anaplastic lymphoma kinase inhibitors in a teaching hospital: A retrospective cohort study

“…Among them, 47 (50.5%) had experienced at least one episode of bradycardia. The average heart rate of the cohort before alectinib administration was 78.3 (standard deviation [SD], 9.5), which decreased to 64.88 (SD, 12.2) after receiving alectinib [10].…”