What is your preferred first line therapy for ROS1 rearranged metastatic NSCLC without CNS mets?

I would use entrectinib even in the absence of CNS disease. The CNS is the most common site of the progression in crizotinib treated patients. Given the known activity of entrectinib in patients with active CNS mets (intracranial ORR of 55%, median duration of intracranial response of 12.9 months), ...

I think this is a particularly difficult question, but in the end, I generally would lean towards crizotinib. The TRK inhibitor toxicities including lightheadedness/dizziness can be difficult, and overall there does not seem to be a clear benefit of entrectinib over crizotinib (outside of entrectini...

Entrectinib.

Crizotinib.

Updated Answer 6/1/2026

I wrote about this earlier (https://www.themednet.org/v2/question/28820), but with newer ROS1 tyrosine kinase inhibitors such as taletrectinib, repotrectinib, and emerging data with zidesamtinib, I personally don't think there is any role for crizotinib or entrectinib in the m...