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ALK rearrangement in advanced NSCLC: alectinib (ALEX, Peters 2017) and lorlatinib (CROWN,...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDBMA-ALK-FUSION-NSCLC
TypeActionability
Statusreviewed 2026-04-27 | pending_clinical_signoff | actionability review required
DiseasesDIS-NSCLC
SourcesSRC-CIVIC SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025

Actionability Facts

BiomarkerBIO-ALK-FUSION
Variantfusion (gene-level, TKI-naive)
DiseaseDIS-NSCLC
ESCAT tierIA
Recommended combinationsalectinib monotherapy (1L), lorlatinib monotherapy (1L, preferred for CNS disease), brigatinib monotherapy (1L)
Contraindicated monotherapycrizotinib (inferior to 2nd/3rd-gen ALK-TKIs, no longer 1L)
Evidence summaryALK rearrangement in advanced NSCLC: alectinib (ALEX, Peters 2017) and lorlatinib (CROWN, Solomon 2024 — 5-yr PFS 60%) outperform crizotinib 1L. Lorlatinib has the highest CNS activity. Adjuvant alectinib improves DFS post-resection (ALINA, Solomon 2024).

Notes

ESCAT IA. OncoKB Level 1. ~5% NSCLC adenocarcinoma. Detection by RNA-NGS / FISH / IHC (D5F3). EML4-ALK most common partner; variant type (v1 vs v3) influences resistance pattern and TKI selection.

Used By

No reverse references found in the YAML corpus.