Newly Approved NSCLC Diagnostic Assay Accurately Assesses for Treatment Options

An immunohistochemistry (IHC) test for rearrangements of the gene for anaplastic lymphoma kinase (ALK) receptor performed more accurately than another commonly used IHC assay, including reducing the rate of false positives. The test was recently approved by the US Food and Drug Administration to identify patients with non-small cell lung cancer (NSCLC) who are eligible for treatment with tyrosine kinase inhibitors of ALK.1

In approximately 3% to 5% of patients with NSCLC, ALK rearrangements can be detected. Most of these cases are adenocarcinomas. For patients with adenocarcinoma NSCLC, screening for ALK rearrangements is routine and necessary to determine eligibility for ALK tyrosine kinase inhibitor therapy.

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Researchers, led by Antonio Marchetti, MD, PhD, University of Chieti, Italy, compared the Ventana ALK (D5F3) CDx assay with OptiView Amplification Kit (Ventana Medical Systems; Tucson, Arizona) with a standard IHC test with the clone 5A4 in more than 1,000 NSCLC adenocarcinoma samples. All tests were also assessed with fluorescence in situ hybridization (FISH). Any discrepancies between IHC and FISH results were resolved with next-generation sequencing.

The Ventana ALK (D5F3) CDx IHC assay had a sensitivity of 90.9% ± 2.6%, and a specificity of 99.8% ± 0.6%, when FISH was used as a reference. Its positive predictive value was 93.8% ± 2.1% and its negative predictive value was 99.7% ± 0.6%.

The commonly used clone 5A4-based IHC test had a sensitivity of 90.9% ± 2.6% and a specificity of 98.3% ± 1.3%, when FISH was used as a reference. Its positive predictive value was 63.8% ± 4.2% and its negative predictive value was 99.7% ± 0.6%.

This study indicated a response rate to ALK inhibitors in 100% of FISH-negative/IHC-positive cases (n=7) and in 46% of FISH-positive/IHC-negative cases (n=13 of 28 cases). This study supported performing a direct diagnosis in approximately 90% of patients by the Ventana ALK (D5F3) CDx assay in the absence of a confirmatory FISH test.

"The large consecutive series examined in this study, unlike several other studies conducted on limited number of cases selected by FISH, highlighted this Achilles heel of the standard IHC test with the 5A4 antibody and showed the possibility of overcoming the problem with the Ventana system that completely ruled out these false positive results," stated the authors.

"These data indicate the important role of IHC in the selection of patients for anti-ALK treatment. However, in order to ensure no ALK-positive patients are left behind, it may be worth considering additional diagnostic tests for equivocal cases."

REFERENCE

1. Marchetti A, Di Lorito A, Pace MV, et al. ALK protein analysis by IHC staining after recent regulatory changes: a comparison of two widely used approaches, revision of the literature, and a new testing algorithm. J Thorac Oncol. doi:10.1016/j.jtho.2015.12.111.

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