%0 Journal Article
%T Cardiac Toxicity of Alectinib in Patients With ALK+ Lung Cancer: Outcomes of Cardio-Oncology Follow-Up.
%A Pruis MA
%A Veerman GDM
%A Hassing HC
%A Lanser DAC
%A Paats MS
%A van Schaik RHN
%A Mathijssen RHJ
%A Manintveld O
%A Dingemans AC
%J JACC CardioOncol
%V 5
%N 1
%D Feb 2023
%M 36875894
%F 8.422
%R 10.1016/j.jaccao.2022.09.006
%X <B>UNASSIGNED: </B>Anaplastic lymphoma kinase (ALK) translocations in metastatic non-small cell lung cancer (3% to 7%) predict for response to ALK-inhibitors (eg, alectinib, first line), resulting in a 5-year survival rate of ∼60% and median progression-free survival of 34.8 months. Although the overall toxicity rate of alectinib is acceptable, unexplained adverse events, including edema and bradycardia, may indicate potential cardiac toxicity.<BR><B>UNASSIGNED: </B>This study's aim was to investigate the cardiotoxicity profile and exposure-toxicity relationship of alectinib.<BR><B>UNASSIGNED: </B>Between April 2020 and September 2021, 53 patients with ALK-positive non-small cell lung cancer treated with alectinib were included. Patients starting with alectinib after April 2020 underwent a cardiac work-up at start, at 6 months and at 1 year at the cardio-oncology outpatients' clinic. Patients already receiving alectinib >6 months underwent 1 cardiac evaluation. Bradycardia, edema, and severe alectinib toxicity (grade ≥3 and grade ≥2 adverse events leading to dose modifications) data were collected. Alectinib steady-state trough concentrations were used for exposure-toxicity analyses.<BR><B>UNASSIGNED: </B>Left ventricular ejection fraction remained stable in all patients who underwent an on-treatment cardiac evaluation (n = 34; median 62%; IQR: 58%-64%). Twenty-two patients (42%) developed alectinib-related bradycardia (6 symptomatic bradycardia). One patient underwent a pacemaker implantation for severe symptomatic bradycardia. Severe toxicity was significantly associated with a 35% higher alectinib mean Ctrough (728 vs 539 ng/mL, SD = 83 ng/mL; 1-sided P = 0.015).<BR><B>UNASSIGNED: </B>No patients showed signs of a diminished left ventricular ejection fraction. Alectinib caused more bradycardia than previously reported (42%) with some instances of severe symptomatic bradycardia. Patients with severe toxicity generally had an elevated exposure above the therapeutic threshold.