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Diagnostic assays for identification of anaplastic lymphoma kinase-positive non-small cell lung cancer
Andrew J Weickhardt1, Dara L Aisner, Wilbur A Franklin
1Division of Medical Oncology, University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, Colorado, USA. andrew.weickhardt@ucdenver.edu
Abstract:
In series dominated by adenocarcinoma histology, approximately 5% of non-small cell lung cancers (NSCLCs) harbor an anaplastic lymphoma kinase (ALK) gene rearrangement. Crizotinib, a tyrosine kinase inhibitor with significant activity against ALK, has demonstrated high response rates and prolonged progression-free survival in ALK-positive patients enrolled in phase 1/2 clinical trials. In 2011, crizotinib received accelerated approval from the US Food and Drug Administration (FDA) for the treatment of proven ALK-positive NSCLC using an FDA-approved diagnostic test. Currently, only break-apart fluorescence in situ hybridization testing is FDA approved as a companion diagnostic for crizotinib; however, many other assays are available or in development. In the current review, the authors summarize the diagnostic tests available, or likely to become available, that could be used to identify patients with ALK-positive NSCLC, highlighting the pros and cons of each.
Insights
Anaplastic lymphoma kinase (ALK) gene rearrangements occur in 5% of non-small cell lung cancers (NSCLC). This review summarizes diagnostic tests for identifying ALK-positive NSCLC patients eligible for targeted therapies like crizotinib.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Approximately 5% of non-small cell lung cancers (NSCLC) feature anaplastic lymphoma kinase (ALK) gene rearrangements.
- Crizotinib, an ALK tyrosine kinase inhibitor, shows high efficacy in ALK-positive NSCLC patients.
- FDA approved crizotinib in 2011 for ALK-positive NSCLC, requiring an FDA-approved diagnostic test.
Purpose of the Study:
- To review currently available and emerging diagnostic tests for identifying ALK-positive NSCLC.
- To highlight the advantages and disadvantages of various ALK detection assays.
- To inform clinical practice regarding companion diagnostics for ALK-targeted therapy.
Main Methods:
- Literature review of diagnostic assays for ALK gene rearrangements in NSCLC.
- Analysis of FDA-approved and investigational diagnostic tests.
- Comparative assessment of assay performance characteristics.
Main Results:
- Currently, only break-apart fluorescence in situ hybridization (FISH) is FDA-approved as a companion diagnostic for crizotinib.
- Numerous other diagnostic assays are available or under development for ALK detection.
- Each assay presents unique pros and cons regarding sensitivity, specificity, and practicality.
Conclusions:
- Accurate ALK rearrangement testing is crucial for selecting NSCLC patients for crizotinib therapy.
- The landscape of ALK diagnostic testing is evolving, with new technologies emerging.
- Clinicians should be aware of the available options and their limitations to optimize patient care.
