Choosing a First-Line ROS1 Inhibitor Across Practice Settings

Estelamari Rodriguez, MD, MPH, Julia K. Rotow, MD, and Ana I. Velázquez Mañana, MD, MSc, explain how they choose among guideline-preferred ROS1 tyrosine kinase inhibitors (TKIs) for first-line treatment of non-small cell lung cancer (NSCLC), in a discussion moderated by Matthew A. Gubens, MD, MS. Dr. Rodriguez favors starting with the agent offering the best efficacy, brain activity, and coverage of resistance mutations rather than reserving it for later. Dr. Rotow sees no current role for crizotinib or entrectinib as new starts and cites progression-free survival of about 3 years with repotrectinib and approaching 4 years with taletrectinib, which she considers the best to date. She flags off-target tropomyosin receptor kinase (TRK) inhibition, which causes dizziness, balance problems, and memory changes, at higher rates with repotrectinib than with taletrectinib or zidesamtinib. Dr. Velázquez Mañana notes that insurance often constrains choices in community practice and that generalists rarely see ROS1-positive disease, making testing company alerts and drug-matching tools valuable resources.