How do you approach a patient with good PS and no treatment contraindications who has progressed on a RET inhibitor for NSCLC?

The management approach will be similar to how we approach patients receiving targeted therapy, i.e. oligoprogression vs widespread progression. Multimodality approaches with surgery or radiation to consolidate residual disease or oligoprogressing sites may enable patient to remain on the same targe...

I would usually perform repeat testing on patients who have progressed on a targeted agent and often utilize ctDNA testing. If the ctDNA testing if unrevealing, I discuss with the patient proceeding with tissue biopsy.

With that being said, there is no validated approach to sequencing RET TKIs base...

Generally, I would perform repeat molecular sequencing after progression on targeted therapy though the data regarding mechanisms of resistance to RET inhibitors is limited. Try and obtain both tissue biopsy and liquid biopsy if feasible.