How do you manage end-organ toxicity such as hepatotoxicity or pulmonary toxicity in a patient receiving RET-inhibitors for NSCLC?

For liver toxicity, I would hold the TKI for grade 3 of higher elevations in the transaminases, and monitor 3-5 days thereafter and then weekly. If the LFTs resolve, I would resume the TKI at a dose reduction. If the LFTS remain normal a couple weeks after resolution, I might even consider dose re-e...

Usually with drug hold. If the toxicity is low grade rechallenge the patient at a lower dose. If it is grade 3 or 4 switch RET inhibitors or switch to chemotherapy.

Standard approaches (drug withdrawal, steroids, IVIG, etc) in management are typically employed. As there are two agents in the market, the question of whether switching from one drug to another arises. There is sufficient structural similarity between selpercatinib and pralsetinib that raises conce...