Intracranial Activity and Brain Surveillance With ROS1 Inhibitors

Matthew A. Gubens, MD, MS, Julia K. Rotow, MD, and Estelamari Rodriguez, MD, MPH, discuss how intracranial activity shapes treatment in ROS1-positive non-small cell lung cancer (NSCLC), a disease with tropism for the brain. Dr. Rotow notes that modern agents achieve central nervous system response rates that mirror systemic rates, and she starts systemic therapy first for brain metastases that are not large, symptomatic, or in a concerning location, adding radiation later if needed. She prefers taletrectinib in the first-line setting and monitors with interval brain magnetic resonance imaging (MRI). Dr. Rodriguez repeats imaging at 6 to 8 weeks, then images every 3 months for patients with baseline brain metastases and at least every 6 months for others. She avoids repotrectinib in patients with brain metastases because its neurologic toxicity can mimic metastatic symptoms, and she works with radiation oncologists to spare young patients brain radiation. Dr. Gubens questions whether repotrectinib dose reductions compromise intracranial activity.