Assay Identifies Crizotinib-Eligible Lung Cancer Patients

An immunohistochemical (IHC) assay for anaplastic lymphoma kinase (ALK) status in non-small cell lung cancer (NSCLC) tumor tissue predicts crizotinib treatment outcomes and offers a rapid and potentially less expensive alternative to older fluorescent in-situ hybridization (FISH) ALK status assays, confirm findings from a validation study published by Ventana Medical Systems, the assay’s manufacturer. The research was reported in the Journal of Thoracic Oncology.

In November 2016, the US Food and Drug Administration (FDA) approved the IHC-based VENTANA ALK (D5F3) CDx Assay which is the only stand-alone companion biomarker predictive for treatment outcome. The study was submitted to the journal in October 2016.

“This automated assay provides an effective option to accurately and rapidly identify patients with ALK-positive NSCLC,” the authors concluded. “The simple binary scoring algorithm results in high reader-to-reader precision. … The assay is highly reproducible and is suitable for use as a stand-alone test to identify NSCLC patients who may benefit from crizotinib treatment.”

A total of 1,018 NSCLC tumor samples that had been prospectively tested for ALK status using FISH as part of the PROFILE 1014 clinical study of crizotinib versus chemotherapy, identifying 179 ALK-positive specimens. These samples were then re-evaluated using the company’s ALK (D5F3) CDx IHC assay and results were analyzed for progression-free survival (PFS) hazard ratios and concordance with FISH ALK assay results.

Of the 1,018 samples, results of both the FISH and ALK (D5G3) CDx IHC assays were available for 933, the authors reported. Overall agreement was 94.3% between the two assays. The IHC assay exhibited a higher rate of “first-pass” interpretation, reducing repeated testing, which should translate to lower overall costs and faster reporting of results to oncologists. It can also use fewer tumor cells than the number required for FISH-based assessments.

“There were 53 discrepant cases of which 25 were ALK^FISH+/IHC- and 28 were ALK^FISH-/IHC+,” the team reported. Inter-reader agreement rates for three independent labs “exceeded 98%” for the ALK IHC assay.

Because the PROFILE 1014 trial had enrolled only patients determined to be ALK-positive using FISH assay, there was no available clinical outcome data for the 28 patients harboring ALK^FISH-/IHC+ tumors, the authors noted. Half of ALK^FISH-/IHC+ tumors exhibited intratumoral heterogeneity.

The objective tumor response rate (ORR) was significantly higher patients with for ALK^FISH-/IHC+ tumors than those with ALK^FISH+/IHC- cancers (86.7% vs 33.3%; P = .0083). Because some ALK^FISH-/IHC+ tumors did not respond to crizotinib, their discordance might represent FISH assay false-negatives rather than false IHC assay-positive results, the authors suggested.

The ALK (D5F3) IHC assay is in use for patient selection in clinical trial settings and findings from those studies will “further evaluate” the assay’s predictive utility, the authors reported.