Companion Diagnostic Tests for Immunotherapy Could Be Switched

A study presented at the ongoing annual meeting of the American Association for Cancer Research has confirmed that 3 commercially available diagnostic tests that measure the expression of the programmed death ligand 1 (PD-L1) protein in non-small cell lung cancer (NSCLC) could be interchanged.

The comparative study was conducted by scientists at AstraZeneca, who evaluated about 500 biopsy samples from patients diagnosed with NSCLC. The tumor samples were assessed using 3 PD-L1 diagnostic tests:

• Ventana SP263 assay (used in the durvalumab clinical trials)
• Dako 28-8 assay (used in the nivolumab Checkmate 057 trial)
• Dako 22C3 assay (used in the pembrolizumab Keynote 001 trial)

“Before our study, we did not know whether the different assays identified the same patients,” said Marianne Ratcliffe, MA, PhD, diagnostic associate director at AstraZeneca, and lead author on the study, in a statement. Ratcliffe said that the tests were developed on different platforms and use different antibody clones and testing protocols.

“Clearly, for the oncology community, this presents a number of issues, including a lack of confidence in being able to identify appropriate patients for treatment with these targeted therapies,” Ratcliffe said. “Our current study complements the ongoing Blueprint initiative, which is also tackling the issue of PD-L1 assay harmonization.”

All 3 immunohistochemistry tests that were evaluated in this study, assess the percentage of tumor cells whose membranes stain positive for PD-L1 expression. Based on a cut-off point for percentage expression, patients who score above the cut-off are considered highly likely to respond to treatment. According to a press release, the patient population defined by the Ventana test at the 25% cutoff point was similar to the group identified by the Dako 28-8 test at the 10% cutoff. Dako 22C3 showed concordance with the Ventana SP263 assay at the 50% cutoff point for both tests.

According to Ratcliffe, these results prove that results can be extrapolated across these diagnostic tests, as long as the cutoff points are indicated. This could prove useful in comparing results from clinical trials that have used different diagnostic tests.

Reference

Ratcliffe MJ, Sharpe A, Midha A, Barker C, Scorer P, Walker J. A comparative study of PD-L1 diagnostic assays and the classification of patients as PD-L1 positive and PD-L1 negative. Paper presented at: American Association of cancer Research Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=4017&sKey=826269b3-49e3-449d-b2cc-5a95aafb9aa4&cKey=e4bad415-dca3-4c43-99f1-3074111fba83&mKey=1d10d749-4b6a-4ab3-bcd4-f80fb1922267. Accessed April 19, 2016.