Activation of ALK (Anaplastic Lymphoma Kinase) through chromosomal rearrangements (inversions and translocations) that fuse various 5’ partners with the 3’ kinase domain of ALK have been described in several malignancies, including Non-Small Cell Lung Cancer (NSCLC). In lung cancer the most common 5’ fusion partner for ALK is EML4 (Echinoderm Microtubule-associated protein-Like 4), but two other fusion partners, KIF5B and TFG, have also been reported. Such fusions cause abnormal ALK kinase activity thought to be oncogenic.
Since the ALK tyrosine kinase activity is necessary for its oncogenicity, several ALK kinase inhibitors have been identified and are being evaluated as potential therapies.
ALK Inhibition in NSCLC
In November 2012, the European Medicines Agency (EMA) approved Xalkori (Crizotinib®, Pfizer) for the treatment of patients with locally advanced or metastatic NSCLC that is positive for ALK translocations.
The approval was based on two single-arm trials, Study A (N = 136 patients) and Study B (N = 119 patients). Crizotinib was administered orally twice daily to a total of 255 patients with locally advanced or metastatic ALK-positive NSCLC.
The primary endpoint of both trials was objective response rate (ORR) as assessed by the investigator. In Study A, the ORR was 50% with a median response duration of 42 weeks. In Study B, the ORR was 61% with a median response duration of 48 weeks. Complete responses were observed in 1 percent of patients.
Information for test processing
To request ALK testing, the first point of contact is the dedicated Lab 21 Customer Services Team who handle:
- Test Requests and Customer Support
- Liaison with Sample Retention Sites for sample retrieval if required
- Reporting of the results
ALK testing by the use of a CE-marked, FDA approved fluorescence in situ hybridization (FISH) method is available from Lab 21. Full requirements for sample preparation can be seen on the sample handling instructions.