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PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays
Harriet Evans1, Brendan O'Sullivan1, Frances Hughes1
1Molecular Pathology Diagnostic Service, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.
Abstract:
Immune checkpoint blockade (ICB) drugs are a novel, effective treatment for advanced urothelial carcinoma. Worldwide, several different ICB drugs are approved, each developed and clinically validated with a specific PD-L1 compound diagnostic assay. As a result, PD-L1 testing workflows in routine practice are complex: requiring multiple assays across two platforms, with each assay having a different method of interpretation. Our service tested 1,401 urothelial carcinoma cases for PD-L1 expression, using both the 22C3 PharmDx assay (required prior to Pembrolizumab therapy) and SP142 assay (required prior to Atezolizumab therapy). Of the 1,401 cases tested, 621 cases (44%) were tested with both the 22C3 PharmDx and SP142 assays, 492 cases (35%) with 22C3 PharmDx only, and 288 cases (21%) with SP142 only. Each assay was used and interpreted according to the manufacturer's guidelines. The rate of positivity we observed was 26% with the 22C3 assay and 31% with the SP142 assay, similar to the pre-licensing studies for both drugs. The discrepancy observed between the assays was 11%, which reinforces the requirement for utilisation of the correct assay for each agent, and limits potential cross-utility of assays. This aspect must be considered when setting up a PD-L1 testing strategy in laboratories where both Pembrolizumab and Atezolizumab are available for the treatment of urothelial carcinoma but also has broader implications for testing of other cancers where multiple ICB drugs and their respective assays are approved.
Insights
Immune checkpoint blockade (ICB) drugs for urothelial carcinoma require specific PD-L1 testing. This study found significant discrepancies between the 22C3 and SP142 assays, highlighting the need for correct assay selection in clinical practice.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Immune checkpoint blockade (ICB) drugs represent a significant advancement in treating advanced urothelial carcinoma.
- Multiple ICB drugs are approved globally, each validated with a distinct PD-L1 companion diagnostic assay.
- This necessitates complex PD-L1 testing workflows in clinical practice, involving multiple assays and interpretation methods.
Purpose of the Study:
- To evaluate PD-L1 expression in urothelial carcinoma using two distinct companion diagnostic assays: 22C3 PharmDx and SP142.
- To assess the concordance and discrepancy rates between these assays in a real-world clinical setting.
- To underscore the importance of appropriate assay selection for specific ICB therapies.
Main Methods:
- Retrospective analysis of 1,401 urothelial carcinoma cases tested for PD-L1 expression.
- Utilized both the 22C3 PharmDx assay (for Pembrolizumab) and the SP142 assay (for Atezolizumab) according to manufacturer guidelines.
- Cases were tested with one or both assays, with interpretation following established protocols.
Main Results:
- PD-L1 positivity rates were 26% for the 22C3 assay and 31% for the SP142 assay.
- An 11% discrepancy rate was observed between the two assays.
- A significant proportion of cases (44%) were tested with both assays, while others were tested with only one.
Conclusions:
- The observed discrepancies between the 22C3 and SP142 assays confirm their limited cross-utility.
- Accurate PD-L1 testing requires strict adherence to the specific assay recommended for each ICB drug.
- This finding has critical implications for laboratory testing strategies, particularly in institutions offering multiple ICB treatment options.
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