Association Between ALK Tyrosine Kinase Inhibitor and the Risk of Interstitial Lung Disease and Pneumonitis in Non-Small Cell Lung Cancer Patients: A Systematic Review
Author(s)
Jiaxing Zhang, Doctor Degree.
Guizhou Provincial People's Hospital, Guiyang, China.
Guizhou Provincial People's Hospital, Guiyang, China.
OBJECTIVES: Interstitial lung disease (ILD) and pneumonitis are specific adverse events of anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs). This study aims to investigate the association between ALK-TKIs and the risks of ILD and pneumonitis in patients with NSCLC.
METHODS: We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) from inception to April 2024 that reported the event of ILD or pneumonitis. We performed pairwise and network meta-analyses with a frequentist fixed effects model. Outcomes were overall/serious ILD and pneumonitis.
RESULTS: A total of 14 RCTs involving 3859 participants (7 ALK-TKIs and chemotherapy) were included. Results from the pairwise meta-analysis showed that ALK-TKIs significantly increased the risks of both overall ILD (RD=0.01, 95%CI: 0.00 to 0.02, P=0.048) and overall pneumonitis (RD=0.01, 95%CI: 0.00 to 0.02, P=0.039) compared to chemotherapy, while no significant difference existed in the risks of both serious ILD (RD=0.01, 95%CI: -0.00 to 0.02, P=0.130) and serious pneumonitis (RD=0.01, 95%CI: -0.00 to 0.02, P =0.109) between ALK-TKIs and chemotherapy. In the network meta-analysis (NMA), brigatinib was associated with significantly higher risks of both overall ILD and overall pneumonitis than crizotinib (OR=8.87, 95%CI: 1.07 to 73.29; OR=3.43, 95%CI: 1.00 to 11.71, respectively), alectinib (OR=12.78, 95%CI: 1.56 to 104.98; OR=6.09, 95%CI:1.57 to 23.68, respectively) and ceritinib (OR=32.50, 95%CI: 1.05 to 1005.95; OR=21.88, 95%CI: 1.78 to 268.53, respectively). Furthermore, the NMA revealed that brigatinib was associated with a significantly higher risk of serious pneumonitis compared to ceritinib (OR=27.26, 95%CI: 1.33 to 558.33). According to P-score results, brigatinib presented the highest risk ranks of both overall/serious ILD and serious pneumonitis.
CONCLUSIONS: ALK-TKIs increase the risks of both ILD and pneumonitis in NSCLC patients, with brigatinib posing the highest risks among ALK-TKIs.
METHODS: We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) from inception to April 2024 that reported the event of ILD or pneumonitis. We performed pairwise and network meta-analyses with a frequentist fixed effects model. Outcomes were overall/serious ILD and pneumonitis.
RESULTS: A total of 14 RCTs involving 3859 participants (7 ALK-TKIs and chemotherapy) were included. Results from the pairwise meta-analysis showed that ALK-TKIs significantly increased the risks of both overall ILD (RD=0.01, 95%CI: 0.00 to 0.02, P=0.048) and overall pneumonitis (RD=0.01, 95%CI: 0.00 to 0.02, P=0.039) compared to chemotherapy, while no significant difference existed in the risks of both serious ILD (RD=0.01, 95%CI: -0.00 to 0.02, P=0.130) and serious pneumonitis (RD=0.01, 95%CI: -0.00 to 0.02, P =0.109) between ALK-TKIs and chemotherapy. In the network meta-analysis (NMA), brigatinib was associated with significantly higher risks of both overall ILD and overall pneumonitis than crizotinib (OR=8.87, 95%CI: 1.07 to 73.29; OR=3.43, 95%CI: 1.00 to 11.71, respectively), alectinib (OR=12.78, 95%CI: 1.56 to 104.98; OR=6.09, 95%CI:1.57 to 23.68, respectively) and ceritinib (OR=32.50, 95%CI: 1.05 to 1005.95; OR=21.88, 95%CI: 1.78 to 268.53, respectively). Furthermore, the NMA revealed that brigatinib was associated with a significantly higher risk of serious pneumonitis compared to ceritinib (OR=27.26, 95%CI: 1.33 to 558.33). According to P-score results, brigatinib presented the highest risk ranks of both overall/serious ILD and serious pneumonitis.
CONCLUSIONS: ALK-TKIs increase the risks of both ILD and pneumonitis in NSCLC patients, with brigatinib posing the highest risks among ALK-TKIs.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO20
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Clinician Reported Outcomes, Comparative Effectiveness or Efficacy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology, Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)