PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project

doi:10.1016/j.jtho.2016.11.2228

Journal of Thoracic Oncology

Volume 12, Issue 2, February 2017, Pages 208-222

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Abstract

Introduction

The Blueprint Programmed Death Ligand 1 (PD-L1) Immunohistochemistry (IHC) Assay Comparison Project is an industrial-academic collaborative partnership to provide information on the analytical and clinical comparability of four PD-L1 IHC assays used in clinical trials.

Methods

A total of 39 NSCLC tumors were stained with four PD-L1 IHC assays (22C3, 28-8, SP142, and SP263), as used in the clinical trials. Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity. Clinical diagnostic performance was assessed through comparisons of patient classification above and below a selected expression cutoff and by agreement using various combinations of assays and cutoffs.

Results

Analytical comparison demonstrated that the percentage of PD-L1–stained tumor cells was comparable when the 22C3, 28-8, and SP263 assays were used, whereas the SP142 assay exhibited fewer stained tumor cells overall. The variability of immune cell staining across the four assays appears to be higher than for tumor cell staining. Of the 38 cases, 19 (50.0%) were classified above and five (13%) were classified below the selected cutoffs of all assays. For 14 of the 38 cases (37%), a different PD-L1 classification would be made depending on which assay/scoring system was used.

Conclusions

The Blueprint PD-L1 IHC Assay Comparison Project revealed that three of the four assays were closely aligned on tumor cell staining whereas the fourth showed consistently fewer tumor cells stained. All of the assays demonstrated immune cell staining, but with greater variability than with tumor cell staining. By comparing assays and cutoffs, the study indicated that despite similar analytical performance of PD-L1 expression for three assays, interchanging assays and cutoffs would lead to “misclassification” of PD-L1 status for some patients. More data are required to inform on the use of alternative staining assays upon which to read different specific therapy-related PD-L1 cutoffs.

Keywords

Immunotherapy

Lung cancer

PD-L1 assays

Immunohistochemistry

Cited by (0)

: Drs. McElhinny and Stanforth equally contributed to this work.

: Disclosure: Dr. Hirsch has received compensation from Genentech/Roche, Pfizer, Bristol-Myers Squibb, Lilly, Merck & Co., Inc., AstraZeneca, Boehringer-Ingelheim, and Ventana/Roche for participating in advisory boards and has received research funding (through the University of Colorado) from Genetech/Roche, Bristol-Myers Squibb, Lilly, Bayer, Amgen, and Ventana/Roche. Mr. Stanforth is a full-time employee of Dako and owns stock in Dako. Dr. Ranger-Moore is a full-time employee of and owns stock in Roche. Ms. Jansson is a full-time employee of and owns stock in Dako. Dr. Kulangara is a full-time employee of and owns stock in Dako. Mr. Richardson and his spouse are full-time employees of Roche. Ms. Towne is a full-time employee of Ventana Medical Systems, Roche Tissue Diagnostics, and owns stock in Roche Diagnostics. Dr. Hanks is a full-time employee of and owns stock in Dako. Dr. Vennapusa is a full-time employee of Ventana Medical Systems, Roche Tissue Diagnostics. Dr. Mistry is a full-time employee of Ventana Medical Systems, Inc., and owns stock in F. Hoffmann-La Roche Ltd. Dr. Kalamegham is a full-time employee of Genentech Inc. Dr. Averbuch is a full-time employee of Bristol-Myers Squibb. Dr. Novotny is a full-time employee of Bristol-Myers Squibb. Dr. Rubin is a full-time employee of Merck & Co., Inc. Dr. Emancipator is a full-time employee of Merck & Co., Inc. and owns stock in Merck & Co., Inc., Bayer AG, and Johnson and Johnson. Dr. McCaffery's spouse was an employee and stockholder of Genentech/Roche during the writing of this study. Dr. Williams is an employee of Genentech. Dr. Walker is a full-time employee of and owns stock in AstraZeneca. Dr. Longshore has performed contract research for Agilent Technologies and Ventana; has received compensation from Ventana, AstraZeneca, Bristol-Myers Squibb, and Genentech for participating in advisory boards; and has received consultancy fees and/or honoraria from Ventana, AstraZeneca, Bristol-Myers Squibb, Genentech, and Merck & Co., Inc. Dr. Tsao has received compensation from AstraZeneca, Merck & Co., Inc., Ventana/Roche, and Bristol-Meyers Squibb for participating in advisory boards and has received research funding (through the University Health Network) from Merck & Co., Inc., Canada. Mr. Kerr has received consultancy fees and/or honoraria from Roche/Genentech, AstraZeneca, Bristol-Myers Squibb, Merck & Co., Inc., and Ventana. The remaining author declares no conflict of interest.