High incidence and reversible bradycardia events following alectinib initiation

Abstract

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.

Keywords

• anaplastic lymphoma kinase
• alectinib
• bradycardia
• non‐small‐cell lung cancer