EML4-ALK variant 3 is associated with shorter PFS on 2nd-gen ALK-TKIs (crizotinib/alectin...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-ALK-EML4-V3-NSCLC |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-NSCLC |
| Sources | SRC-CIVIC SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Actionability Facts
| Biomarker | BIO-ALK-FUSION |
|---|---|
| Variant | EML4-ALK variant 3 (E6;A20) |
| Disease | DIS-NSCLC |
| ESCAT tier | IA |
| Recommended combinations | lorlatinib monotherapy (preferred for v3), alectinib monotherapy (alternative) |
| Evidence summary | EML4-ALK variant 3 is associated with shorter PFS on 2nd-gen ALK-TKIs (crizotinib/alectinib) and a higher rate of acquired G1202R resistance. CROWN (Solomon 2024) showed lorlatinib 1L delivers uniformly long PFS regardless of variant — making lorlatinib the preferred 1L choice for v3. |
Notes
ESCAT IA. v3 + co-occurring TP53 has worst prognosis — strongest case for lorlatinib 1L. Variant identification requires RNA-NGS; not detectable by IHC alone.
Used By
No reverse references found in the YAML corpus.