Programmed Death Ligand 1 Immunohistochemistry in Triple-Negative Breast Cancer: Evaluation of Inter-Pathologist Concordance and Inter-Assay Variability.

Published on May 26, 2021in Journal of Breast Cancer2.241
· DOI :10.4048/JBC.2021.24.E29
Purpose null The programmed death ligand 1 (PD-L1) SP142 assay with a 1% immune cell (IC) cutoff is approved for the selection of advanced triple-negative breast cancer (TNBC) patients for atezolizumab treatment. We aimed to evaluate the interobserver concordance of PD-L1 scoring and inter-assay variability of various PD-L1 assays in TNBC. null Methods null Thirty patients with primary TNBC were selected, and SP142, SP263, 22C3, and E1L3N assays were performed. PD-L1 staining in ICs and tumor cells (TCs) was scored by 10 pathologists who were blinded to the assay. The interobserver concordance among pathologists and the inter-assay variability of the four PD-L1 assays were analyzed. For SP142, the intraobserver concordance among the six pathologists was analyzed after training. null Results null The adjusted means of PD-L1 IC scoring ranged from 6.2% to 12.9% for the four assays; the intraclass correlations showed moderate (0.584-0.649) reader concordance. The PD-L1 IC scoring with a 1% cutoff resulted in identical scoring in 40.0%-66.7% of cases and a poor to moderate agreement (Fleiss κ statistic [FKS] = 0.345-0.534) for the four assays. The SP142 assay had the widest range of positive rate (56.5%-100.0%), lowest number of cases with identical scoring, and lowest FKS at 1% cutoff. Pairwise comparison of adjusted means showed significantly decreased PD-L1 staining in SP142 compared with the other assays in both ICs and TCs. As for the intraobserver concordance in the SP142 assay, the overall percent agreement was 87.8% with a 1% IC cutoff. After training, the proportion of cases with identical scoring at a 1% IC cutoff increased to 70.0%; the FKS also increased to 0.610. null Conclusion null The concordance of PD-L1 IC scoring among pathologists was low, at the 1% cutoff for the SP142 assay without training. SP142 showed the lowest PD-L1 expression in both IC and TC.
#1Emily S. Reisenbichler (Yale University)H-Index: 5
#2Gang Han (A&M: Texas A&M University)H-Index: 23
Last. David L. Rimm (Yale University)H-Index: 112
view all 24 authors...
The US Food and Drug Administration (FDA) approved the PD-L1 immunohistochemical assay, SP142, as a companion test to determine eligibility for atezolizumab therapy in patients with advanced triple negative breast cancer (TNBC) but data in lung cancer studies suggest the assay suffers from poor reproducibility. We sought to evaluate reproducibility and concordance in PD-L1 scoring across multiple pathologists. Full TNBC sections were stained with SP142 and SP263 assays and interpreted for percen...
28 CitationsSource
#1Paula I. Gonzalez-Ericsson (VUMC: Vanderbilt University Medical Center)H-Index: 11
#2Elisabeth Specht Stovgaard (UCPH: University of Copenhagen)H-Index: 7
Last. Melinda E. Sanders (VUMC: Vanderbilt University Medical Center)H-Index: 57
view all 75 authors...
Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying >/=1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-rea...
43 CitationsSource
#1Eslie Dennis (Hoffmann-La Roche)H-Index: 2
#2Mark M. KockxH-Index: 55
Last. Ehab E ElGabry (Hoffmann-La Roche)H-Index: 1
view all 6 authors...
BACKGROUND: The VENTANA PD-L1 (SP142) Assay (SP142 assay) is the FDA-approved companion diagnostic for the combination of TECENTRIQ (atezolizumab) and nab-paclitaxel for the treatment of patients with unresectable, locally advanced, or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 - defined as PD-L1 stained tumor-infiltrating immune cells (IC) of any intensity covering ≥ 1 percent of the tumor area. Accurate and reproducible assessment of IC PD-L1 staining with the S...
2 CitationsSource
#1Michelle R Downes (U of T: University of Toronto)H-Index: 6
#2Elzbieta Slodkowska (U of T: University of Toronto)H-Index: 15
Last. Bin Xu (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 25
view all 5 authors...
AIMS: Programmed death-ligand 1 (PD-L1) expression by tumour cells (TC) is a mechanism for tumour immune escape through down-regulation of antitumour T cell responses and is a target for immunotherapy. PD-L1 status as a predictor of treatment response has led to the development of multiple biomarkers with different reference cut-offs. We assessed pathologist consistency in evaluating PD-L1 immunopositivity by examining the inter- and intraobserver agreement using various antibody clones and diff...
17 CitationsSource
#1Hope S. Rugo (UCSF: University of California, San Francisco)H-Index: 107
#2Sherene LoiH-Index: 85
Last. Leisha A. Emens (University of Pittsburgh)H-Index: 54
view all 17 authors...
49 CitationsSource
#1Aurelia Noske (TUM: Technische Universität München)H-Index: 41
#2Johannes Ammann (Hoffmann-La Roche)H-Index: 4
Last. Wilko Weichert (TUM: Technische Universität München)H-Index: 79
view all 13 authors...
Abstract Background Atezolizumab (an anti–PD-L1 antibody) has shown clinical activity alone or in combination with nab-paclitaxel in patients (pts) with first-line metastatic TNBC who have PD-L1 expression on their tumour-infiltrating immune cells (IC). We analysed the performance of 4 PD-L1 IHC assays for PD-L1 IC expression in TNBC. Methods Thirty archival TNBC tissue specimens were selected from a set of 107 based on PD-L1 IC expression per VENTANA SP142 ( 5%: 8 cases), to represent the distr...
5 CitationsSource
#1Kristina Schwamborn (TUM: Technische Universität München)H-Index: 22
#2Johannes Ammann (Hoffmann-La Roche)H-Index: 4
Last. Wilko Weichert (TUM: Technische Universität München)H-Index: 79
view all 12 authors...
Programmed death-ligand 1 (PD-L1) expression on tumor cells (TC) or tumor-infiltrating immune cells (IC) correlated in several studies with PD-L1/programmed death-1 (PD-1) checkpoint inhibitor efficacy. Since June 2018, a positive PD-L1 status is required for atezolizumab or pembrolizumab treatment of patients with advanced or metastasized urothelial bladder cancer, who are ineligible for cisplatin-containing therapy. We examined technical comparability and inter-reader agreement of four clinica...
18 CitationsSource
#1Leonie Voorwerk (NKI-AVL: Netherlands Cancer Institute)H-Index: 6
#2Maarten Slagter (NKI-AVL: Netherlands Cancer Institute)H-Index: 9
Last. Marleen Kok (NKI-AVL: Netherlands Cancer Institute)H-Index: 23
view all 34 authors...
The efficacy of programmed cell death protein 1 (PD-1) blockade in metastatic triple-negative breast cancer (TNBC) is low1–5, highlighting a need for strategies that render the tumor microenvironment more sensitive to PD-1 blockade. Preclinical research has suggested immunomodulatory properties for chemotherapy and irradiation6–13. In the first stage of this adaptive, non-comparative phase 2 trial, 67 patients with metastatic TNBC were randomized to nivolumab (1) without induction or with 2-we...
218 CitationsSource
#1M. Scott (AstraZeneca)H-Index: 6
#2Paul Scorer (AstraZeneca)H-Index: 9
Last. H. Al-MasriH-Index: 2
view all 4 authors...
15 CitationsSource
#1Bharathi Vennapusa (Ventana Medical Systems)H-Index: 6
#2Brian Baker (Ventana Medical Systems)H-Index: 2
Last. Zachary BoydH-Index: 11
view all 20 authors...
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non–small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohist
65 CitationsSource
Cited By0