Approximately one in 20 patients with non-small cell lung carcinoma (NSCLC) has chromosomal aberrations targeting the anaplastic lymphoma kinase (ALK) gene. This has considerable 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 and easy-to-perform 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. It is crucial to the clinical success of ALK inhibitors to identify those patients most likely to benefit from ALK inhibition. The latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology now recommend upfront ALK screening for all patients with NSCLC.
There are several clinically validated methodologies currently 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.
"The FISH assay has undergone extensive validation in clinical setting and is currently the gold standard for ALK fusion detection," say lead investigators Dong-Wan Kim, MD, PhD, Seoul National University Hospital, Seoul, South Korea, and Mao Mao, MD, PhD, Pfizer Oncology, California. "A disadvantage of this diagnostic assay, however, lies in the fact that the signal can be subtle and consequently hard to interpret, requiring specialized technical expertise. It is also considerably more expensive compared with IHC and RT-PCR."