Real-world effectiveness and safety of brigatinib in advanced ALK-positive NSCLC: a nationwide multicenter study by the Turkish Oncology Group

Abstract

BackgroundBrigatinib, a next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor, has demonstrated efficacy in pivotal trials in both pretreated and treatment-na & iuml;ve patients with ALK-positive non-small-cell lung cancer (NSCLC). However, real-world evidence from large multicenter cohorts remains limited.MethodsWe conducted a retrospective multicenter study including 114 patients with advanced ALK-positive NSCLC treated with brigatinib across 28 centers in Turkey between May 2020 and December 2024. Objective response rate (ORR) was assessed by RECIST v1.1. Median progression-free survival (mPFS) and overall survival (mOS) were estimated by the Kaplan-Meier method, and prognostic factors were analyzed using Cox regression.ResultsThe median age was 55 years. Brigatinib was administered as first-line therapy in 68.4% of cases. In the overall cohort, the mPFS and OS were 24.2 and 44.2 months. The ORR was 70.2%. In the first-line setting, the ORR was 79.5%, with an mPFS of 28.6 months and an mOS of 50.3 months. In contrast, those treated in the second-line or later setting had less-favorable outcomes, which independently correlated with worse OS in multivariate analysis. Patients with baseline brain metastases achieved favorable outcomes, with an mPFS of 26.2 months, an mOS of 46.3 months, and an ORR of 76.5%. Adverse events were reported in 83.3% of patients, most commonly gastrointestinal toxicities, creatine phosphokinase elevation, and liver enzyme abnormalities.ConclusionThis nationwide multicenter study offers comprehensive real-world evidence confirming the effectiveness and tolerability of brigatinib in ALK-positive NSCLC, with especially favorable outcomes in the first-line setting and in patients with brain metastases.