PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: This study\'s aim was to investigate the cardiotoxicity profile and exposure-toxicity relationship of alectinib.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: This study\'s aim was to investigate the cardiotoxicity profile and exposure-toxicity relationship of alectinib.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
摘要：
未经证实：转移性非小细胞肺癌中的间变性淋巴瘤激酶（ALK）易位（3％至7％）可预测对ALK抑制剂的反应（例如，阿列替尼,第一行),5年生存率为60%，中位无进展生存期为34.8个月。尽管阿来替尼的总体毒性率是可以接受的，无法解释的不良事件，包括水肿和心动过缓,可能表明潜在的心脏毒性。
非ASSIGNED：本研究的目的是调查阿来替尼的心脏毒性和暴露毒性关系。
UNASSIGNED：在2020年4月至2021年9月之间，纳入了53例接受阿来替尼治疗的ALK阳性非小细胞肺癌患者。在2020年4月之后开始使用alectinib的患者在开始时接受了心脏检查，在心脏肿瘤门诊患者的6个月和1年时。已经接受alectinib>6个月的患者接受1次心脏评估。心动过缓,水肿,收集阿来替尼严重毒性(导致剂量调整的≥3级和≥2级不良事件)数据.阿莱替尼稳态谷浓度用于暴露毒性分析。
UNASSIGNED：所有接受治疗心脏评估的患者的左心室射血分数保持稳定（n=34；中位数为62％；IQR：58％-64％）。22例患者(42%)发生了阿来替尼相关的心动过缓(6例有症状的心动过缓)。一名患者因严重症状性心动过缓而接受了起搏器植入。严重毒性与阿来替尼平均Ctugh高出35%显著相关(728比539ng/mL，SD=83ng/mL；单侧P=0.015）。
未经证实：没有患者出现左心室射血分数降低的迹象。阿莱替尼引起的心动过缓比以前报道的更多（42％），并有一些严重的症状性心动过缓。具有严重毒性的患者通常具有高于治疗阈值的升高的暴露。
非ASSIGNED：本研究的目的是调查阿来替尼的心脏毒性和暴露毒性关系。
UNASSIGNED：在2020年4月至2021年9月之间，纳入了53例接受阿来替尼治疗的ALK阳性非小细胞肺癌患者。在2020年4月之后开始使用alectinib的患者在开始时接受了心脏检查，在心脏肿瘤门诊患者的6个月和1年时。已经接受alectinib>6个月的患者接受1次心脏评估。心动过缓,水肿,收集阿来替尼严重毒性(导致剂量调整的≥3级和≥2级不良事件)数据.阿莱替尼稳态谷浓度用于暴露毒性分析。
UNASSIGNED：所有接受治疗心脏评估的患者的左心室射血分数保持稳定（n=34；中位数为62％；IQR：58％-64％）。22例患者(42%)发生了阿来替尼相关的心动过缓(6例有症状的心动过缓)。一名患者因严重症状性心动过缓而接受了起搏器植入。严重毒性与阿来替尼平均Ctugh高出35%显著相关(728比539ng/mL，SD=83ng/mL；单侧P=0.015）。
未经证实：没有患者出现左心室射血分数降低的迹象。阿莱替尼引起的心动过缓比以前报道的更多（42％），并有一些严重的症状性心动过缓。具有严重毒性的患者通常具有高于治疗阈值的升高的暴露。
