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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.”
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.
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.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
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.
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.
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.
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.
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.
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.
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.”
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.
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.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
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.”
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.
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.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCLC 2016
Key clinical point:
Major finding: The concordance weighted kappa coefficient was highest for tests using the SP263 antibody, with an average coefficient of 0.81.
Data source: Forty-one non–small cell lung cancer specimens subjected to a total of 35 different tests.
Disclosures: Funding for the study came from AstraZeneca, Bristol Myers Squibb, Merck Sharp and Dohme, and Roche. Dr. Adam has been a consultant to AstraZeneca, Bristol-Myers Squibb, HalioDx, Merck Sharp and Dohme, and Roche. Dr. Gadgeel has been a speaker on behalf of Eli Lilly, Genentech, and GlaxoSmithKline and has received research funding from AstraZeneca, Eli Lilly, and Genentech. Dr. Brahmer has served on an advisory board for Merck.