Approximately one in 20 patients with non-small cell lung carcinoma (NSCLC) has chromosomal aberrations targeting the anaplastic lymphoma kinase (ALK) gene. This has implications for treatment because these patients are highly responsive to ALK-specific kinase inhibitors such as crizotinib. However, current diagnostic tests have limitations. Researchers have now developed and tested a promising new method for screening ALK fusions in NSCLC. This new diagnostic assay offers a cost-effective alternative to existing tests. The study is published in The Journal of Molecular Diagnostics.
Crizotinib is a protein tyrosine kinase inhibitor approved by the FDA for the treatment of locally advanced or metastatic ALK-positive NSCLC as detected by an FDA-approved test and is undergoing phase III clinical trials. The latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology now recommend upfront ALK screening for all patients with NSCLC.
Several clinically validated methodologies are available for the detection of ALK fusions, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcription-polymerase chain reaction (RT-PCR). Crizotinib-centered clinical trials currently utilize a FISH-based test that was recently approved by FDA as the standard companion diagnostic test for crizotinib. However, it is complex and has considerable limitations in terms of cost and throughput, making it difficult to screen large numbers of patients.
In the early phase trial of crizotinib, approximately 1,500 patients were screened by FISH to identify 82 ALK-positive patients. The large number of patients qualifying for screening underscores the need for a high throughput and cost- effective screening modality. To explore alternative screening modalities for detecting ALK fusions, researchers designed a method for detecting ALK fusions by direct, multiplexed transcript profiling using the gene expression platform from NanoString. They tested their assay in 66 archival NSCLC samples which had been independently tested by both FISH and IHC methods in terms of sensitivity, specificity, reproducibility, and concordance to prior FISH and IHC.
The results were highly concordant to previous results obtained by FISH and IHC and the investigators were able to successfully detect low-level ALK fusion transcripts in samples with low tumor cell content. All samples predicted to be positive in the assay responded favorably to crizotinib.??”While further testing on a larger sample size is needed for this assay to be considered in clinical practice, we have demonstrated that it offers a cost-effective, easy to perform, high-throughput, and FFPE-compatible screening alternative for detecting ALK fusions,” conclude the investigators.
[source: Elsevier Health Sciences]