Abstract
PURPOSE: To assess the possible effect of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) on the health-related quality of life (HRQoL) in patients with ALK-positive non-small cell lung cancer (NSCLC). METHODS: A systematic search was performed in PubMed, Web of Science, Embase, and ClinicalTrials.gov to identify literature published between January 2010 and January 2025. Publications reported quantitative assessments of HRQoL in ALK-positive NSCLC patients treated with ALK-TKIs were included. Meta-analyses were performed using random effect models. RESULTS: A total of 805 records were identified, of which 21 were analyzed in the meta-analysis. Compared to crizotinib, next-generation ALK-TKIs showed statistically significant delayed time to deterioration (TTD) in global health status measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.67 to 0.96). Brigatinib and alectinib demonstrated superior TTD in fatigue symptom score of EORTC QLQ-C30 compared to crizotinib (HR: 0.71; 95% CI: 0.54 to 0.92). Regarding between-arm comparisons from baseline, brigatinib and lorlatinib outperformed crizotinib in global health status, physical and emotional functioning, and symptoms scores of nausea and vomiting, fatigue, constipation, and appetite loss using EORTC QLQ-C30. CONCLUSIONS: This study is by far the most comprehensive systematic review and meta-analysis on HRQoL among ALK-positive NSCLC patients treated with ALK-TKIs. These findings extended prior literature by conducting a granular comparison of all available ALK-TKIs across multiple endpoints and highlighted the improved performance of next-generation ALK-TKIs in enhancing HRQoL for ALK-positive NSCLC patients.