Abstract 4015: A comparative study of PD-L1 IHC 22C3 and 28-8 FDA-approved diagnostic assays in cancer
Authors: Batenchuk Cory , Albitar Maher , Sudarsanam Sucha , Chizhevsky Vladislav , Jin Chelsea , Burns Virginia A. 
Published: July 2017

Abstract
Background: Higher levels of PD-L1 expression at the surface of tumor cells have been associated with increased response to anti-PD-1 therapies (Santabarbara G et al. Ann Transl Med. 2016;4:215; Borghaei H et al. N Engl J Med. 2015;373:1627-1639; Brahmer J et al. N Engl J Med. 2015;373:123-135). The FDA has 2 approved tests associated with the use of these agents. The Dako PD-L1 IHC 22C3 kit is approved as a companion diagnostic for the use of pembrolizumab in the first- and second-line non-small-cell lung cancer (NSCLC) settings, where diagnostic testing is required for its use. The Dako PD-L1 IHC 28-8 kit is approved as a complementary diagnostic for nivolumab therapy in second-line NSCLC, where testing is not required for its use. NeoGenomics Laboratories stained a subset of the samples received for PD-L1 testing with both 22C3 and 28-8 on the same biopsy specimen. This dataset presents an opportunity to explore real-world concordance testing for 22C3 and 28-8 antibodies.
Methods: The analysis was performed on a dataset obtained from Symphony Health Solutions describing the PD-L1 biomarker test results and annotations reported by NeoGenomics Laboratories between Oct 7, 2015, and Aug 31, 2016. A total of 5217 biomarker test results were available for 4528 patients afflicted by diverse malignancies. Concordance testing was performed on 556 unique patients that had a single 22C3/28-8 pairing collected from the same biopsy specimen. All staining was performed using the FDA-approved in vitro diagnostic assay using the 22C3 antibody or the 28-8 antibody on the Dako Link 48. Cases were reviewed and scored randomly across multiple pathologists, who received special training and certification in scoring. All statistical analyses were performed in SAS.
Results: Paired biopsy specimens stained with both 22C3 and 28-8 displayed high degrees of correlation (Spearman’s correlation co-efficient = 0.97). In addition, Bland-Altman analysis revealed that the mean difference in the percentage of tumor cells positively stained for PD-L1 between the paired 22C3 and 28-8 assay findings was 0.48% [95% prediction limit (-12.41% to 13.37%)]. Across expression levels both antibodies displayed a similar probability of being interpreted as greater than one another (43 of 556 where 28-8&gt;22C3 and 40 of 556 where 22C3&gt;28-8), with no clear direction of a single antibody displaying greater sensitivity. When analyzed at the ≥ 1%, ≥ 5%, ≥ 10%, ≥ 25% and ≥ 50% thresholds, the overall rate of agreement was between 96.8% and 98.2% and associated with a level of agreement (Cohen’s kappa) between 0.92 and 0.96.
Conclusion: Both the 22C3 and 28-8 diagnostic assays show strong agreement in a single central laboratory real-world setting. These data, in conjunction with recent findings from analytical comparability studies reported elsewhere, support the potential interchangeability of these assays for diagnostic interpretation.
Citation Format: Cory Batenchuk, Maher Albitar, Sucha Sudarsanam, Vladislav Chizhevsky, Chelsea Jin, Virginia A. Burns. A comparative study of PD-L1 IHC 22C3 and 28-8 FDA-approved diagnostic assays in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4015. doi:10.1158/1538-7445.AM2017-4015