Conference Coverage

PD-L1 testing in NSCLC patients shows high concordance

Publish date: January 17, 2017
By
Mitchel L. Zoler, PhD
MDedge News

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NSCLC treatment needs PD-L1 test harmonization

Researchers have developed several different antibodies for measuring levels of PD-L1 in tumor cells and the antibodies can be used in several different testing platforms. Although most laboratories focus on using one specific immunohistochemical platform, the overall status of real-world PD-L1 testing is messy.

In the results reported by Dr. Adam, concordance weighted kappa coefficients of 0.8 or higher show extremely good concordance, and coefficients of 0.6-0.79 show good concordance. Several of the tests and testing sites reported by Dr. Adam showed concordance coefficients within these ranges. In certain other cases the concordance coefficients were very low, which prompts concern about the reliability of these low-scoring tests. The results show that the results you see in one laboratory with a specific antibody and platform test may not always remain consistent with the same antibody and platform used elsewhere.

Dr. Michael Boyer speaks during the World Conference on Lung Cancer Mitchel L. Zoler/Frontline Medical News

Dr. Michael Boyer

Testing for PD-L1 is important because right now it is how we identify patients with metastatic non–small cell lung cancer who are candidates for first-line pembrolizumab treatment. Knowing how individual laboratories perform PD-L1 testing and having confidence in the results is very important for managing these patients. We need to understand what individual laboratories do and what their results mean. A close collaboration between clinicians and pathologists is needed to optimize patient care.

Michael Boyer, MD, is a professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from AstraZeneca, Bristol-Myers Squibb, Clovis, Eli Lilly, Pfizer, and Roche. He made these comments as designated discussant for the report.


 

AT WCLC 2016

VIENNA – Several different tests for PD-L1 levels in tumor cells of patients with metastatic non–small cell lung cancer showed high concordance when run at seven French centers, boosting confidence in the clinical utility of this testing to guide first-line pembrolizumab treatment of patients with this cancer.

Among 27 laboratory-developed tests for PD-L1 (programmed death–ligand 1) levels in tumor cells that used any one of three prespecified testing platforms (made by Dako, Ventana, or Leica), 14 (52%) had “similar” concordance when compared with reference assays, Julien Adam, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer. “These results will provide the basis for making national recommendations for PD-L1 testing in patients with non–small cell lung cancer [NSCLC]” in France, added Dr. Adam, a pathologist at Gustave Roussy Cancer Center in Paris. “We expect to produce recommendations by the second half of 2017.”

Dr. Julien Adam speaks during the World Conference on Lung Cancer Mitchel L. Zoler/Frontline Medical News

Dr. Julien Adam

Several single-center studies had examined harmonization of several different PD-L1 tests, but the new, multicenter study examined several different antibodies and platforms systematically, he noted.

Although the results came entirely from French centers, the results will also likely influence U.S. practice, predicted Shirish M. Gadgeel, MD, a thoracic oncologist at the Karmanos Cancer Institute in Detroit. The approval pembrolizumab (Keytruda) received from the Food and Drug Administration in October specified that patients with metastatic NSCLC had to show PD-L1 expression in the tumor using a FDA-approved test to receive pembrolizumab as first-line treatment.

“Before pembrolizumab’s approval there was no incentive to do PD-L1 testing,” but now it is becoming routine, he said. “It has been challenging to U.S. laboratories to decide which platform and antibody to use. Harmonization gives us confidence that if you have a platform and appropriate antibody you should be able to use the results clinically. I think the French results can be extrapolated” to U.S. practice because the results “came from multiple labs using multiple antibodies and platforms,” Dr. Gadgeel said.

Dr. Julie R. Brahmer speaks during the World Conference on Lung Cancer Mitchel L. Zoler/Frontline Medical News

Dr. Julie R. Brahmer

The new French study “is unique by being very real-world, in one country across multiple institutions,” commented Julie R. Brahmer, MD, director of thoracic oncology at the Johns Hopkins Kimmel Cancer Center in Baltimore. “It behooves every physician [caring for advanced NSCLC patients] to know what a PD-L1 test means when they get a result.” An ongoing effort to assess performance of PD-L1 testing at U.S. centers began in late 2015 by the National Comprehensive Cancer Network.

The French study arranged for PD-L1 testing of NSCLC specimens from 41 patients selected as broadly representative of PD-L1 expression levels. The seven participating centers used a Dako (three centers), Ventana (two centers), or Leica (two centers) testing platform and one of five available antibodies that bind PD-L1. Every center ran tests that depended on different antibodies, and tests occurred on both tumor cells and immune cells. In total the seven testing sites collectively performed 35 stainings on each specimen for a total of 1,435 slides. In tumor cells, the overall, weighted kappa coefficient for concordance was 0.81 for tests that used the SP263 antibody and 0.78 for those using the E1L3N antibody, both high enough to make them potential candidates for routine use, said Dr. Adam. The 28-8 and 22C3 antibodies also showed high concordance levels. In contrast, some antibodies used at certain centers produced unacceptable results with concordance coefficients of less than 0.5. The best performing antibody overall was SP263.

No test measuring PD-L1 level in immune cells had an acceptable concordance rate, Dr. Adam also reported.

On Twitter @mitchelzoler

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