Summary of ALK testing recommendations from major international guidelines1-4

Please refer to the full guidelines as necessary for more information.1-4

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ESMO1
Testing for ALK rearrangement biomarkers should be systematically carried out for patients with advanced non-squamous NSCLC.1

IHC has become the accepted equivalent alternative to FISH for ALK testing and the recommended approach to determine primary targeted therapy, provided this method is validated against another independent test, such as FISH.1

NGS is an emerging technology that has been rapidly and widely implemented to screen patients with NSCLC.1,2 This testing method enables the sequencing of a high number of nucleotides in a short timeframe and at an affordable cost.2 However, NGS does not address ALK at the protein level as seen with FISH and IHC.1 The question remains as to whether the ALK fusion genes detected by NGS require validation against another independent test.1

Based on current evidence, the routine use of NGS is recommended to identify ALK rearrangements in patients with advanced non-squamous NSCLC.1,2

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NCCN3
Molecular testing for ALK rearrangements is recommended in patients with advanced and metastatic squamous and non-squamous NSCLC to determine targeted TKI therapy.3

FISH, IHC and NGS tests are recommended methods for detecting ALK gene fusions. IHC can be used for rapid pre-screening for ALK fusions.3 One IHC assay (ALK [D5F3] CDx Assay) is an FDA-approved test that does not require confirmation by FISH.3

NGS can also be used to assess for ALK fusions, provided they are appropriately designed and validated for detection of ALK fusions.3 Targeted real-time PCR tests are also recommended but unlikely to detect novel ALK fusion partners.3

Patients with NSCLC should not be selected for testing based on clinicopathologic features associated with ALK rearrangement, such as smoking status and histology.3

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CAP/IASLC/AMP4
All patients with advanced non-squamous NSCLC with an adenocarcinoma component should be tested for ALK rearrangements.4

The FISH test is recommended to detect ALK rearrangement and novel fusion partners. IHC is recommended as an equivalent alternative to FISH.4

RT-PCR and NGS tests have shown comparable performance with IHC when designed to detect the majority of ALK gene fusions and are standard practice in many countries.4

The excellent sensitivity of NGS relative to single-gene tests has been demonstrated in multiple studies. NGS also enables simultaneous assessment of ALK, EGFR and ROS1 fusion genes, and hundreds to thousands of other genes that could play a role in cancer development.4 

NGS is the recommended testing alternative to FISH and IHC to identify ALK rearrangements and inform targeted therapy decisions1-4

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ALK: anaplastic lymphoma kinase; AMP: Association for Molecular Pathology; CAP: College of American Pathologists; ESMO: European Society for Medical Oncology; FDA: Food & Drug Administration; FISH: fluorescence in situ hybridization; IHC: immunohistochemistry; IASLC: International Association for the Study of Lung Cancer; NCCN: National Comprehensive Cancer Network; NGS: next generation sequencing; NSCLC: non-small-cell lung cancer; PCR: polymerase chain reaction; RT-PCR: reverse transcription-polymerase chain reaction; TKI: tyrosine kinase inhibitor.