Elsevier

Journal of Thoracic Oncology

Volume 13, Issue 9, September 2018, Pages 1302-1311
Journal of Thoracic Oncology

Original Article
Translational Oncology
PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project

https://doi.org/10.1016/j.jtho.2018.05.013Get rights and content
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Abstract

Objectives

The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples.

Methods

BP2 were conducted using 81 lung cancer specimens of various histological and sample types, stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10); the slides were evaluated by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by using digital images, and samples prepared for cytological examination. PD-L1 expression was assessed for percentage (tumor proportional score) of tumor cell (TC) and immune cell areas showing PD-L1 staining, with TCs scored continuously or categorically with the cutoffs used in checkpoint inhibitor trials.

Results

The BP2 results showed highly comparable staining by the 22C3, 28-8 and SP263 assays; less sensitivity with the SP142 assay; and higher sensitivity with the 73-10 assay to detect PD-L1 expression on TCs. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient [ICC] = 0.86–0.93), poor reliability in IC PD-L1 scoring (overall ICC = 0.18–0.19), and good agreement in assessing PD-L1 status on cytological cell block materials (ICC = 0.78–0.85).

Conclusion

BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.

Keywords

Immunooncology
Checkpoint inhibitors
Companion diagnostics
Complementary diagnostics
Cytology
Pathology

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Disclosure: Dr. Tsao reports grants and personal fees from AstraZeneca, Merck, and Pfizer and personal fees from Bristol-Myers Squibb and Ventana/Roche outside the submitted work. Dr. Kerr reports personal fees from Bristol-Myers Squibb, Merck Sharp and Dohme, Merck Serono, Roche, and AstraZeneca outside the submitted work. Dr. Beasley reports pathology consulting work from Genentech, Bristol-Myers Squibb, and Merck outside the submitted work. Dr. Botling reports personal fees from AstraZeneca, Merck Sharp and Dohme, Roche, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, and Novartis outside the submitted work. Dr. Bubendorf reports grants and personal fees from Roche and Merck Sharp and Dohme and personal fees from Bristol-Myers Squibb and AstraZeneca during the conduct of the study. Dr. Dacic reports personal fees from Bristol-Myers-Squibb and AstraZeneca outside the submitted work. Dr. Lantuejoul reports grants and personal fees from Bristol-Myers Squibb and personal fees from Merck Sharp and Dohme, Roche, and Novartis outside the submitted work. Dr. Mina-Kenudson reports personal fees from Merrimack Pharmaceuticals, H3 Biomedicine, ACD, and Roche outside the submitted work. Dr. Moreira reports personal fees from Genetech outside the submitted work. Dr. Nicholson reports personal fees from Merck, Boehringer Ingelheim, Novartis, AstraZeneca, Bristol-Myers Squibb, Roche, AstraZeneca, and AbbVie and grants and personal fees from Pfizer outside the submitted work. Dr. Poleri reports personal fees from AstraZeneca, Merck, Roche, and Bristol-Myers Squibb outside the submitted work. Dr. Sauter reports stock ownership in Merck, Thermo Fischer Scientific, and Chemed Corporation outside the submitted work. Dr. Thunnissen reports personal fees from HistoGeneX and Ventana Roche during the conduct of the study. Dr. Wistuba reports grants and personal fees from Genentech/Roche, Bristol-Myers Squibb, Astra Zeneca/Medimmune, Pfizer, HTG Molecular, and Merck; personal fees from Boehringer Ingelheim, Medscape, Asuragen, GlaxoSmithKline, and Bayer; and grants from Oncoplex, DepArray, Adaptive, Adaptimmune, Takeda, Amgen, and EMD Serono outside the submitted work. Dr. Yatabe reports personal fees from Merck Sharp and Dohme, Chugai-pharm, AstraZeneca, Pfizer, and Novartis outside the submitted work. Dr. Hirsch is coinventor of a University of Colorado–owned patent titled: “EGFR IHC and. FISH as Predictive Biomarkers for EGFR Therapy.” Dr. Hirsch has participated in advisory boards for Bristol-Myers Squibb, Genentech/Roche, HTG, Lilly, Merck, Pfizer, and Ventana. Dr. Hirsch's laboratory has received research grants (through the University of Colorado) from Genentech, Bristol-Myers Squibb, Lilly, Bayer, and Clovis. The remaining authors declare no conflict of interest.