Central Nervous System Progression in Patients Receiving ALK-Targeted Central Nervous System-Penetrable Tyrosine Kinase Inhibitors: Treatment Patterns and Outcomes.

Abstract

Central nervous system (CNS) metastases are common in ALK-rearranged NSCLC. The optimal treatment strategy for patients who develop CNS progression during treatment with CNS-penetrable ALK tyrosine kinase inhibitors (TKIs) is unknown. Here, we characterized practice patterns and outcomes for patients who developed CNS progression during treatment with CNS-penetrable TKI.This retrospective study included patients who developed CNS progression (time 0, [T0]) on alectinib, lorlatinib, brigatinib, or ensartinib. Patients were characterized according to TKI management (i.e., TKI unaltered, TKI-altered [switched TKI or increased TKI dose], TKI discontinued) at T0. Intracranial progression-free survival was evaluated using Kaplan-Meier and compared using the log-rank test.Among 98 patients treated with a CNS-penetrable TKI, 36 (37%) experienced CNS progression. Overall, 33 (92%) developed parenchymal and seven (19%) developed leptomeningeal progression, respectively. At T0, 16 (44%) had TKI unaltered, 14 (39%) had TKI altered (eight switched TKI, six increased TKI dose), and six (17%) discontinued TKI. Patients with TKI-altered tended to have more frequent leptomeningeal disease or concurrent systemic progression at T0. Intracranial radiation was given at T0 in 14 (88%) of TKI-unaltered and three (21%) of TKI-altered patients. The median intracranial progression-free survival from T0 was not significantly different between the TKI-altered versus unaltered groups (p = 0.21).For patients with ALK-rearranged NSCLC with leptomeningeal progression or concurrent systemic progression, TKI change or dose increase was a feasible salvage strategy for CNS progression during treatment with CNS-penetrable TKI.

View details for DOI 10.1016/j.jtocrr.2025.100914

View details for PubMedID 41256965

View details for PubMedCentralID PMC12621429