How do you determine your next line of therapy In ALK+ metastatic NSCLC patients who have widespread progression on first-line lorlatinib?

In general, with TKIs, it is critical to consider mechanisms of resistance. Broadly speaking, these can be categorized as on-target (e.g., ALK G1202R), off-target (e.g., MET gene amplification), or histologic/EMT changes (e.g., small cell transformation). Lorlatinib has excellent coverage of many on...

Biopsy (both liquid and tissue) can be informative - especially to ensure there is no histologic transformation to small cell or squamous cell - so I try this when feasible. If a specific mechanism of resistance is identified, it can guide treatment decisions. ALK-resistant mutations make next-gener...