Assessment of Immunohistochemistry Assays for PD-L1 Expression in NSCLC
In a study of four immunohistochemistry programmed cell death ligand 1 (PD-L1) expression assays registered with the U.S. Food and Drug Administration (FDA), scoring was highly concordant for expression in tumor cells but poorly concordant for scoring in immune cells in non–small cell lung cancer (NSCLC) samples. These findings were reported by Rimm et al in JAMA Oncology.
Study Details
In the study, 4 serial histologic sections from 90 archival NSCLC samples obtained from January 2008 to December 2010 were distributed to 3 sites that performed the following assays: 28-8 antibody on the Dako Link 48 platform (FDA cleared, used for nivolumab [Opdivo]); 22c3 antibody on the Dako Link 48 platform (FDA cleared, used for pembrolizumab [Keytruda]); SP142 antibody on the Ventana Benchmark platform (investigational use assay; a newer slightly altered assay, now FDA-approved, is used for atezolizumab [Tecentriq]); and a laboratory-developed test using E1L3N antibody on the Leica Bond platform. Slides were scanned and scored by 13 pathologists.
Scoring Results
Results with the SP142 assay differed from the other assays, yielding significantly lower mean scores for PD-L1 expression on both tumor cells (1.99 vs 2.96 using 22c3 antibody, 3.26 using 28-8 antibody, and 3.20 using E1L3N antibody) and immune cells (1.62 vs 2.15 with 22c3, 2.28 with 28-8, and 2.28 with E1L3N). For tumor cells, scores with the 28-8 and E1L3N tests did not significantly differ, but the 22c3 test yielded slightly but significantly lower scores (mean difference = 0.24–0.30) compared with the 28-8 and E1L3N tests.
Concordance
Calculation of intraclass correlation coefficients to measure interassay variability showed high concordance among antibodies for tumor cell scoring (0.813) and low concordance for immune cell scoring (0.277). Assessment of variability among pathologists showed high concordance for each assay (range = 0.832–0.882) for tumor cells and low concordance (0.172–0.229) for immune cells.
The investigators concluded: “The assay using the SP142 antibody is an outlier that detected significantly less PD-L1 expression in tumor cells and immune cells. The assay for antibody 22c3 showed slight yet statistically significantly lower staining than either 28-8 or E1L3N, but this significance was detected only when using the mean of 13 pathologists’ scores. The pathologists showed excellent concordance when scoring tumor cells stained with any antibody but poor concordance for scoring immune cells stained with any antibody. Thus, for tumor cell assessment of PD-L1, 3 of the 4 tests are concordant and reproducible as read by pathologists.”
The study was funded by Bristol-Myers Squibb in collaboration with the National Comprehensive Cancer Network Oncology Research Program.
David L. Rimm, MD, PhD, of Yale University School of Medicine, is the corresponding author of the JAMA Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
