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This algorithm covers systemic therapy for stage IV non-small cell lung cancer with a confirmed ALK rearrangement. All first-line options are CNS-penetrant ALK tyrosine kinase inhibitors. Lorlatinib is the preferred first-line agent (CROWN) and is noted to have the deepest intracranial activity. Alectinib (ALEX) and brigatinib (ALTA-1L) are shown as first-line alternatives.
At progression, the later-line branch offers lorlatinib as a next-generation ALK inhibitor for patients who did not receive it first-line, and platinum plus pemetrexed as the cytotoxic option after TKI therapy. The chart notes that immunotherapy is ineffective in ALK-positive disease, so checkpoint inhibitors do not appear on either branch. The overall sequence is therefore ALK inhibition first, ideally with the most CNS-active agent, followed by a next-generation inhibitor if available and then platinum-pemetrexed chemotherapy. This is a simplified board-review scaffold that should be checked against current guidelines and primary literature.
Background reading: NSCLC (Part 2): Stage IV, Targeted and Systemic Therapy board review notes.
First-line ALK TKIs (CNS-penetrant) then later-line options. Starting point: Stage IV NSCLC ALK rearrangement confirmed. Full background: NSCLC (Part 2): Stage IV, Targeted and Systemic Therapy notes.
Simplified board-prep scaffold; verify against current guidelines and primary literature. ALK TKIs are CNS-penetrant: lorlatinib has the deepest intracranial activity; immunotherapy is ineffective in ALK-positive disease.