Central Nervous System Progression in Patients Receiving ALK-Targeted Central Nervous System-Penetrable Tyrosine...

Area of Science:

• Oncology
• Neurology
• Pharmacology

Background:

• Central nervous system (CNS) metastases are frequent in Anaplastic Lymphoma Kinase (ALK)-rearranged Non-Small Cell Lung Cancer (NSCLC).
• Optimal treatment for CNS progression during CNS-penetrable ALK tyrosine kinase inhibitor (TKI) therapy remains unclear.
• This study investigates clinical practice patterns and outcomes for such patients.

Purpose of the Study:

• To characterize treatment strategies and outcomes for patients with ALK-rearranged NSCLC who experience CNS progression while on CNS-penetrable ALK TKIs.
• To evaluate the effectiveness of altering TKI management (dose adjustment or switch) versus maintaining the current TKI or discontinuing it.

Main Methods:

• Retrospective analysis of 98 patients with ALK-rearranged NSCLC who developed CNS progression on alectinib, lorlatinib, brigatinib, or ensartinib.
• Patients were categorized based on TKI management at the time of CNS progression: unaltered, altered (switched or dose increased), or discontinued.
• Intracranial progression-free survival (PFS) was assessed using Kaplan-Meier analysis and compared with the log-rank test.

Main Results:

• 37% (36/98) of patients experienced CNS progression, with most developing parenchymal (92%) versus leptomeningeal (19%) disease.
• At CNS progression, 44% had unaltered TKI, 39% had altered TKI (switch/dose increase), and 17% discontinued TKI.
• Intracranial PFS was not significantly different between TKI-altered and TKI-unaltered groups (p=0.21), though TKI-altered patients had more frequent leptomeningeal/systemic progression.

Conclusions:

• Altering TKI therapy by switching or increasing the dose is a feasible salvage strategy for CNS progression in ALK-rearranged NSCLC.
• This approach may be particularly relevant for patients with leptomeningeal or concurrent systemic progression.
• Further research is warranted to optimize TKI management in this patient population.