Abstract
BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality worldwide. Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) presents unique clinical challenges, including frequent central nervous system (CNS) metastases. At present, comparative real-world data on ALK inhibitors remain limited. This study aimed to compare real-world progression-free survival (PFS) and overall survival (OS) among patients with ALK-positive NSCLC treated with first-line alectinib or brigatinib using nationwide South Korean data. METHODS: This retrospective cohort study analyzed anonymized data from South Korea's Health Insurance Review and Assessment Service, covering January 2007 to December 2023. Patients diagnosed with ALK-positive NSCLC (ICD-10: C34x) and treated with either alectinib or brigatinib as first-line monotherapy were included. Patients with prior lung surgery or other malignancies were excluded. Baseline demographics and comorbidities were collected. The primary outcomes were PFS and OS, as measured from ALK inhibitor initiation. RESULTS: The final cohort included 1,009 patients with ALK-positive NSCLC. The mean age was 61.6 years, and 49.5% were male. Alectinib was associated with a significantly longer PFS. Brigatinib showed a higher OS in the unadjusted analysis; however, this difference was not statistically significant after multivariable adjustment. Transition to lorlatinib was associated with extended survival in both groups, reflecting its use as a later-line therapy following resistance. CONCLUSIONS: In this real-world cohort of ALK-positive NSCLC patients, both alectinib and brigatinib were associated with extended survival, with alectinib showing longer PFS. Findings should be interpreted descriptively. Alectinib demonstrated superior disease control in terms of PFS. Further research is warranted to optimize treatment sequence strategies for ALK inhibitors.