Real-World Treatment Patterns and Sequencing of ALK-Inhibitors in ALK-Positive NSCLC Treated with Palliative Intent

Background: ALK-rearranged non-small cell lung cancer (NSCLC) is a molecularly defined subtype that is highly sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors). With multiple generations of ALK inhibitors available, real-world data on treatment patterns and sequencing in routine clinical practice remain limited. Methods: This retrospective multicenter registry analysis included patients with ALK-positive NSCLC treated with palliative intent and enrolled in the LALUCA registry between November 2020 and September 2025 at four lung cancer centers in Vienna. ALK alterations were confirmed by next-generation sequencing. Demographic, clinical, and treatment-related data were analyzed descriptively. Results: Twenty-eight patients were included (median age, 54 years [range, 26–84]; 46.4% female). Most patients had stage IV disease (85.7%) and adenocarcinoma histology (92.9%). Overall, 49 systemic treatment lines were administered, including 41 ALK inhibitor treatment lines (22 second-generation and 19 third-generation). At data cut-off, 39.0% of ALK inhibitor treatment lines were ongoing, with a higher proportion of ongoing treatment observed among third-generation compared with second-generation ALK inhibitors (52.6% vs. 27.3%). The Kaplan–Meier-estimated median treatment duration was 287 days (95% CI, 172-NE) for second-generation and 736 days (95% CI, 376–NE) for third-generation ALK inhibitors. Objective response rates were 77.3% and 73.7%, respectively. Adverse events of any grade occurred in 73.2% of treatment lines, while grade ≥ 3 adverse events occurred in 12.2%. Dose reductions and temporary treatment interruptions were used to manage toxicity and allowed for treatment continuation in most affected treatment lines. Conclusions: This multicenter real-world analysis provides insights into contemporary ALK inhibitor treatment patterns and sequencing in routine clinical practice. Third-generation ALK inhibitors were associated with longer observed treatment durations in this cohort, although these findings should be interpreted cautiously given the small sample size, retrospective analysis, and potential differences in treatment selection and follow-up. Overall, toxicity was generally manageable, with dose modifications and temporary treatment interruptions frequently allowing for continuation of ALK inhibitor therapy.