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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
PD-L1 expression heterogeneity in non-small cell lung cancer: evaluation of small biopsies reliability
Enrico Munari1,2, Giuseppe Zamboni1, Marcella Marconi1
1Department of Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Italy.
Abstract:
Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay. For the large majority of patients such evaluation is made on small biopsies. However, small tissue samples such as core biopsies might not be representative of tumors and may show divergent results given the possible heterogeneous immunoexpression of the biomarker. We therefore sought to evaluate PD-L1 expression concordance in a cohort of 239 patients using tissue microarrays (TMA) as surrogates of biopsies stained with a validated PD-L1 immunohistochemical assay (SP263) and report the degree of discordance among tissue cores in order to understand how such heterogeneity could affect decisions regarding therapy. We observed a discordance rate of 20% and 7.9% and a Cohen's κ value of 0.53 (moderate) and 0,48 (moderate) for ≥ 1% and ≥ 50% cutoffs, respectively. Our results suggest that caution must be taken when evaluating single biopsies from patients with advanced NSCLC eligible for immunotherapy; moreover, at least 4 biopsies are necessary in order to minimize the risk of tumor misclassification.
Insights
PD-L1 expression in non-small cell lung cancer biopsies can be inconsistent, potentially affecting immunotherapy decisions. At least four biopsies may be needed to accurately classify tumors for treatment eligibility.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Immunotherapy with checkpoint inhibitors, like pembrolizumab, has revolutionized cancer treatment, particularly for non-small cell lung cancer (NSCLC).
- PD-L1 expression levels in tumors guide treatment decisions for NSCLC patients receiving immunotherapy.
- Accurate PD-L1 assessment is crucial, but often relies on small biopsy samples, raising concerns about representativeness due to potential tumor heterogeneity.
Purpose of the Study:
- To evaluate the concordance of PD-L1 expression in advanced non-small cell lung cancer (NSCLC).
- To assess the impact of tumor heterogeneity on PD-L1 assessment using tissue microarrays (TMA) as biopsy surrogates.
- To determine the number of biopsies required to minimize misclassification for immunotherapy eligibility.
Main Methods:
- A cohort of 239 advanced NSCLC patients was analyzed.
- Tissue microarrays (TMA) were used as surrogates for small biopsies.
- PD-L1 immunohistochemical staining was performed using a validated SP263 assay.
Main Results:
- A discordance rate of 20% for the ≥1% PD-L1 expression cutoff and 7.9% for the ≥50% cutoff was observed.
- Moderate agreement (Cohen's κ = 0.53 and 0.48) was found for both cutoffs.
- Analysis suggests that at least four biopsies are necessary to reduce the risk of misclassifying NSCLC patients for immunotherapy.
Conclusions:
- Caution is advised when interpreting PD-L1 expression from single biopsies in advanced NSCLC.
- Tumor heterogeneity can significantly impact PD-L1 assessment and subsequent immunotherapy treatment decisions.
- Utilizing multiple biopsies (at least four) is recommended to improve the accuracy of PD-L1 evaluation and ensure appropriate patient selection for immunotherapy.
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