What would you use as next line of treatment for a patient with ROS1+ metastatic NSCLC progressing on first line TKI?

The finding that crizotinib was quite active in ROS1 altered cancers (Shaw et al., PMID 25264305 - confirmed in East Asian patients - Wu et al., PMID 29596029) obviously altered the practice of thoracic oncology, and led to the approval of crizotinib in patients with ROS1 translocations. Moreover, t...

It depends on the genomics of a patient's tumor at the time of progression. Patients progressing on 1st line TKI should have repeat ctDNA or tumor biopsy if possible. About half of patients have secondary ROS mutations, most commonly G2032R. Lorlatinib and repotrectinib both have activity against th...

There is no strong evidence to suggest moving between crizotinib and entrectinib. Using lorlatinib is reasonable, but the response rate is likely lower than with a platinum doublet, so chemotherapy may be the best choice, especially for symptomatic progression.