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Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Investigation of PD-L1 Biomarker Testing Methods for PD-1 Axis Inhibition in Non-squamous Non-small Cell Lung Cancer
Brandon S Sheffield1, Regan Fulton2, Steve E Kalloger3
1Department of Pathology, Abbotsford Regional Hospital and Cancer Centre, British Columbia, Canada (BSS)
Abstract:
Inhibitors of the programmed cell death 1 (PD-1) signaling axis have recently demonstrated efficacy and are rapidly being incorporated into the treatment of non-small cell lung cancers (NSCLCs). Despite clear benefits to certain patients, the association of these responses with a predictive biomarker remains uncertain. Several different biomarkers have been proposed, with differing results and conclusions. This study compares multiple methods of biomarker testing for treatment of NSCLCs with PD1-axis inhibitors. Tissue microarrays of matched primary and metastatic NSCLCs were used to compare four different PD-1 ligand (PD-L1) IHC techniques, as well as RNA ISH. Additional cases with whole genome and transcriptome data were assessed for molecular correlates of PD-L1 overexpression. Eighty cases were included in the IHC study. Multiple IHC methodologies showed a high rate of agreement (Kappa = 0.67). When calibrated to RNA expression, agreement improved significantly (Kappa = 0.90, p=0.0049). PD-L1 status of primary and metastatic tumors was discordant in 17 (22%) cases. This study suggests that different IHC methodologies for PD-L1 assessment provide slightly different results. There is significant discordance between the PD-L1 status of primary tumors and lymph node metastases. RNA ISH may be a useful adjunct to complement PD-L1 IHC testing.
Insights
Comparing programmed cell death 1 ligand (PD-L1) testing methods for non-small cell lung cancer (NSCLC) revealed significant discordance between primary and metastatic tumors. RNA ISH improved agreement when calibrating immunohistochemistry (IHC) assays.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Research
Background:
- Programmed cell death 1 (PD-1) inhibitors are effective in non-small cell lung cancer (NSCLC) treatment.
- Predictive biomarkers for PD-1 therapy response in NSCLC are still under investigation.
- Various methods exist for assessing PD-1 ligand (PD-L1) expression, a potential predictive biomarker.
Purpose of the Study:
- To compare multiple immunohistochemistry (IHC) techniques for PD-1 ligand (PD-L1) assessment in NSCLC.
- To evaluate the concordance of PD-L1 status between primary and metastatic NSCLC tumors.
- To explore the utility of RNA in situ hybridization (ISH) and molecular data in conjunction with PD-L1 IHC.
Main Methods:
- Utilized tissue microarrays from matched primary and metastatic NSCLC tumors.
- Compared four distinct PD-L1 IHC techniques and RNA ISH.
- Analyzed whole genome and transcriptome data for molecular correlates of PD-L1 expression in a subset of cases.
Main Results:
- High agreement was observed among multiple PD-L1 IHC methodologies (Kappa = 0.67).
- Agreement significantly improved when IHC results were calibrated to RNA expression (Kappa = 0.90, p=0.0049).
- PD-L1 status was discordant between primary and metastatic tumors in 22% of cases (17 out of 80).
Conclusions:
- Different PD-L1 IHC methodologies yield slightly varied results in NSCLC.
- Significant discordance in PD-L1 status exists between primary NSCLC tumors and their metastases.
- RNA ISH may serve as a valuable complementary tool to PD-L1 IHC testing for NSCLC treatment selection.
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