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An ALK fusion, usually EML4::ALK, is a swapped piece of chromosome 2 that turns the ALK kinase on permanently in about 4 percent of lung adenocarcinomas. Seven ALK inhibitors are approved for it, including alectinib after surgery.
ALK rearrangements are detected by break-apart FISH (Vysis), immunohistochemistry (Ventana D5F3), or DNA and RNA sequencing; the FDA list carries all three routes as companion diagnostics. Crizotinib, ceritinib, alectinib, brigatinib, lorlatinib and ensartinib are labelled for ALK-positive metastatic NSCLC 'as detected by an FDA-approved test', and alectinib for adjuvant treatment after resection of tumours 4 cm or larger or node-positive (ALINA). Crizotinib is also labelled for ALK-positive anaplastic large cell lymphoma and inflammatory myofibroblastic tumour. Alectinib's label allows selection on tumour tissue or plasma.
In plain words · ALK is a gene fusion driver in about 4 to 5% of non-small-cell lung cancers that responds to a succession of ALK inhibitor pills. Lorlatinib kept about 60% of patients progression-free at five years, alectinib is approved after surgery, and neladalkib targets compound resistance mutations.
ALK-positive lung cancer is treated first with an ALK tablet, usually alectinib or lorlatinib, instead of chemotherapy or immunotherapy, and responses often last years. After surgery, two years of alectinib is on label for larger or node-positive tumours. If one ALK tablet stops working, others are approved after it.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
An ALK gene rearrangement or fusion by break-apart FISH (15 percent or more of cells with split or isolated 3' signals on the Vysis kit), ALK protein expression by the Ventana D5F3 IHC assay, or a fusion transcript or rearrangement by sequencing of tissue or plasma.
“ALK rearrangements”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| ALK-positive (adjuvant, tumours >= 4 cm or node positive) | Alectinib | Non-small-cell lung cancer | FDA | label |
| ALK-positive | Lorlatinib | Non-small-cell lung cancer | FDA | label |
| ALK-positive or ROS1-positive | Crizotinib | Non-small-cell lung cancer | FDA | label |
| ALK-positive | Brigatinib | Non-small-cell lung cancer | FDA | label |
| ALK-positive, ALK inhibitor-naive | Ensartinib | Non-small-cell lung cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| Vysis ALK Break Apart FISH Probe Kit | Abbott Molecular | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Crizotinib | P110012 (08/26/2011) |
| Vysis ALK Break Apart FISH Probe Kit | Abbott Molecular | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Ensartinib | P110012/S022 (08/05/2025) |
| Ventana ALK (D5F3) CDx Assay | Ventana Medical Systems (Roche) | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Alectinib | P140025/S006 (11/06/2017) |
| Ventana ALK (D5F3) CDx Assay | Ventana Medical Systems (Roche) | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Lorlatinib | P140025/S014 (03/03/2021) |
| FoundationOne CDx | Foundation Medicine | Non-Small Cell Lung Cancer (NSCLC) - Tissue | AlectinibCrizotinibCeritinib | P170019 (11/30/2017) |
| FoundationOne Liquid CDx | Foundation Medicine | Non-Small Cell Lung Cancer (NSCLC) - Plasma | Alectinib | P200006 (10/26/2020) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
It turned the laboratory prediction into a clinical rule: after a second-generation ALK inhibitor, genotype the tumour, and treat the absence of an ALK mutation as evidence that the cancer has stopped depending on ALK.
It is the document that defines what a complete lung cancer molecular report looks like, and its asymmetry about plasma, rule in but never rule out, is the single most useful sentence in it.
ALK is the reason young, KRAS wild-type patients should have fusion testing even though the overall rate is one in six hundred.
It made repeat biopsy and genotyping at progression the standard in ALK-positive lung cancer, because after a second-generation inhibitor the presence or absence of an ALK mutation is what separates patients who should receive a third-generation inhibitor from those who should not.
It is the cleanest demonstration in oncology that resistance is a property of a particular drug bound to a particular protein rather than a property of the tumour, and that genotyping at every progression can reopen an option that looked closed.
It is the study that made multiplex testing standard practice in lung adenocarcinoma, by showing both that most tumours have a driver and that finding it changes what patients receive.
The second driver in lung cancer, and the one that proved the first was not a special case. It also established mutual exclusivity as a working assumption: a tumour usually has one driver, so finding it tells you what to give.
Shares ROS1 fusion (ROS1-positive), RET fusion and RET mutation, NTRK1/2/3 gene fusion, Gene fusion and the tags biomarker, fusion.
Shares Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors, FoundationOne CDx / Liquid CDx, Non-small-cell lung cancer and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Gene fusion and the tag biomarker.
Shares Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma, FoundationOne CDx / Liquid CDx, Pancreatic ductal adenocarcinoma, Non-small-cell lung cancer and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Gene fusion and the tag biomarker.
Shares Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors, FoundationOne CDx / Liquid CDx, Non-small-cell lung cancer and the tag biomarker.
Shares Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors, Non-small-cell lung cancer and the tag biomarker.
Shares Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs, Pancreatic ductal adenocarcinoma, Non-small-cell lung cancer and the tag biomarker.