Dataset Information

Cardiac Toxicity of Alectinib in Patients With ALK+ Lung Cancer: Outcomes of Cardio-Oncology Follow-Up.

ABSTRACT:

Background

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.

Objectives

This study's aim was to investigate the cardiotoxicity profile and exposure-toxicity relationship of alectinib.

Methods

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.

Results

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 C_trough (728 vs 539 ng/mL, SD = 83 ng/mL; 1-sided P = 0.015).

Conclusions

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.

SUBMITTER: Pruis MA

PROVIDER: S-EPMC9982223 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Cardiac Toxicity of Alectinib in Patients With ALK+ Lung Cancer: Outcomes of Cardio-Oncology Follow-Up.

Pruis Melinda A MA Veerman G D Marijn GDM Hassing H Carlijne HC Lanser Daan A C DAC Paats Marthe S MS van Schaik Ron H N RHN Mathijssen Ron H J RHJ Manintveld Olivier O Dingemans Anne-Marie C AC

JACC. CardioOncology 20230117 1

<h4>Background</h4>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.<h4>Objectives</h4>This study's aim was to investiga ...[more]

PMID: 36875894

Similar Datasets

Project description:BackgroundAlectinib, a next-generation anaplastic lymphoma kinase tyrosine kinase inhibitor (ALK-TKI), has demonstrated noteworthy efficacy in the treatment of non-small cell lung cancer (NSCLC). Unfortunately, 53.3% of untreated patients receiving first-line treatment with alectinib developed resistance to alectinib. However, despite the widespread use of alectinib, studies on the efficacy and safety of continuing alectinib with other necessary therapies after progression of alectinib and possible population of benefit are still limited.MethodsThis retrospective cohort study included fifteen patients with ALK-positive NSCLC from nine institutions in China who experienced disease progression after first- or second-line treatment and continued to receive alectinib treatment between 2019 and 2022. This study aimed to evaluate the median progression-free survival (mPFS), objective response rate (ORR), median overall survival (mOS), and adverse events (AEs) of continuing alectinib combined with other therapies after the emergence of drug resistance.ResultsAmong fifteen patients eligible for this study, all patients started continuing treatment with alectinib after oligoprogression or central nervous system (CNS) progression. The mPFS for the whole cohort receiving continuing alectinib with other necessary therapies was 8 months [95% confidence interval (CI): 4 to not applicable (NA)], with an ORR of 46.7%. The mOS was not reached. During continuing alectinib treatment, only one patient experienced grade 2 elevation of aspartate aminotransferase (AST) and serum glutamic-oxaloacetic transaminase (SGOT).ConclusionsThe continuation of alectinib treatment combined with other necessary therapies demonstrates favorable response and safety in patients with ALK-positive NSCLC who experienced oligoprogression or CNS progression following alectinib in first- or second-line therapy. Instead of immediately switching to another ALK-TKI, continuing alectinib combined with other necessary therapies may offer greater survival benefits to the patients.

Dataset Information

Cardiac Toxicity of Alectinib in Patients With ALK+ Lung Cancer: Outcomes of Cardio-Oncology Follow-Up.

Background

Objectives

Methods

Results

Conclusions

Publications

Cardiac Toxicity of Alectinib in Patients With ALK+ Lung Cancer: Outcomes of Cardio-Oncology Follow-Up.

Similar Datasets

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