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.

I would absolutely prefer entrectinib for all patients with ROS1 NSCLC without CNS disease. The morbidity from progressive brain metastases cannot be understated and approximately 50% of patients from our institutional series developed CNS progression on crizotinib [Patil et al., PMID 29981925], con...