Meta-analysis of the incidence and risks of interstitial lung disease and QTc prolongation in non-small-cell lung cancer patients treated with ALK inhibitors.

Liping Lin,Xiaolong Cao,Yan He,Ning Kong,Jiazhu Hu,Juanjuan Zhao,Jianjun Han,Fuxi Huang

doi:10.18632/oncotarget.18283

Abstract

BackgroundTo conduct a systematic review and meta-analysis to assess the overall incidence and risk of interstitial lung disease (ILD) and QTc prolongation associated with anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (-TKIs) in non-small-cell lung cancer (NSCLC) patients.ResultsA total of 1,770 patients from 8 clinical trials were included. The incidences of high-grade ILD and QTc prolongation was 2.5% (95% CI 1.7-3.6%), and 2.8% (95% CI 1.8-4.3%), respectively. Meta-analysis demonstrated that the use of ALK-TKIs in NSCLC patients significantly increased the risk of developing high-grade ILD (Peto OR, 3.27, 95%CI: 1.18–9.08, p = 0.023) and QTc prolongation (Peto OR 7.51, 95% CI, 2.16–26.15; p = 0.002) in comparison with chemotherapy alone.Materials and MethodsA systematic literature search was performed to identify related citations up to January 31, 2017. Data were extracted, and summary incidence rates, Peto odds ratios (Peto ORs), and 95% confidence intervals (CIs) were calculated.ConclusionsThe use of ALK-TKIs significantly increases the risk of developing high-grade ILD and QTc prolongation in lung cancer patients. Clinicians should pay attention to the risks of severe ILD and QTc prolongation with the administration of these drugs.

Highlights

Lung cancer remains the most commonly diagnosed cancer and the leading cause of cancer mortalities globally [1]
Meta-analysis demonstrated that the use of anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients significantly increased the risk of developing highgrade interstitial lung disease (ILD) (Peto odds ratios (ORs), 3.27, 95%confidence intervals (CIs): 1.18–9.08, p = 0.023) and QTc prolongation (Peto OR 7.51, 95% CI, 2.16–26.15; p = 0.002) in comparison with chemotherapy alone
The use of ALK-TKIs significantly increases the risk of developing high-grade ILD and QTc prolongation in lung cancer patients

Summary

Introduction

Lung cancer remains the most commonly diagnosed cancer and the leading cause of cancer mortalities globally [1]. The majority of lung cancer (about 85%) are classified as non-small cell lung cancer (NSCLC) [2]. Many genomic abnormalities, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangements, have been identified in NSCLC. Crizotinib, an oral small-molecule tyrosine kinase inhibitor against ALK, MET and ROS1 kinases, is the first approved ALKinhibitor (ALK-i) by Food and Drug Administration (FDA) as first-line treatment for ALK-positive advanced NSCLC [8]. The development of effective next-generation ALK inhibitors www.impactjournals.com/oncotarget for the advanced NSCLC is desperately needed. To conduct a systematic review and meta-analysis to assess the overall incidence and risk of interstitial lung disease (ILD) and QTc prolongation associated with anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (-TKIs) in non-small-cell lung cancer (NSCLC) patients

Methods

Results

Discussion

Conclusion