# Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance

Source: https://onco.cc/ideas/idea-tnbc-pd-l1-assay-harmonisation/  
OnCo record `idea-tnbc-pd-l1-assay-harmonisation` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Three PD-L1 tests run on the same tumours called 46, 75 and 73 percent of them positive and agreed only 69 percent of the time. With atezolizumab withdrawn, pembrolizumab's test (22C3, combined positive score of 10) is the only one that matters, yet laboratories still run whichever kit they have. One assay, one score and a proficiency scheme would end answers that vary by postcode.

## Summary

Rugo's IMpassion130 analysis of 614 tumours found PD-L1 immune cell positivity of 46.4 percent by SP142, 74.9 by SP263 and 73.1 by 22C3, concordance of 69 percent, and harmonised cut-offs reaching only about 75 percent; atezolizumab's benefit lay in the tumours all three called positive. KEYNOTE-355 selected on 22C3 combined positive score of 10 or more, which the ASCO 2022 biomarker guideline made the recommended test, and the atezolizumab indication was withdrawn in the United States in 2021. Practice has not caught up: SP142 remains in use where atezolizumab was adopted, laboratories score immune cells and combined positive score interchangeably, and scoring of the combined positive score at the 10 threshold has known inter-observer variation. Digital scoring and external quality assurance schemes exist for HER2 and could be extended.

## Fields

- Kind: Idea
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Hypothesis: Mandating 22C3 combined positive score (or a validated equivalent with demonstrated concordance above 90 percent at the 10 threshold) with participation in an external quality assurance scheme will reduce discordant PD-L1 calls between laboratories to under 10 percent and increase the proportion of eligible patients receiving first-line pembrolizumab.
- Rationale: The test decides access to a survival-prolonging drug and the evidence that assays are not interchangeable is direct; harmonisation costs little because the assay already exists and quality assurance infrastructure exists for other breast biomarkers.
- Proposed test: Ring study of 22C3 combined positive score across national laboratories with a reference panel; before-and-after audit of assay use, discordance rate and pembrolizumab uptake after a national harmonisation directive; a digital scoring validation against the reference panel.
- Maturity: early-clinical
- Actor: regulator

## Sources

- Rugo et al.: PD-L1 assay comparison in IMpassion130 (J Natl Cancer Inst 2021): https://europepmc.org/article/MED/34097070

## Connected records

- cancers: [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Digital pathology & AI](https://onco.cc/technologies/digital-pathology-ai/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [VENTANA PD-L1 (SP142) Assay](https://onco.cc/drugs/ventana-pd-l1-sp142/)
- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [National Institute for Health and Care Excellence](https://onco.cc/institutions/nice/)
- terms: [Combined positive score (CPS)](https://onco.cc/terms/cps/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- trials: [IMpassion130](https://onco.cc/trials/impassion130/), [IMpassion131](https://onco.cc/trials/impassion131/), [KEYNOTE-355](https://onco.cc/trials/keynote-355/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Knowledge reaches practice too slowly](https://onco.cc/bottlenecks/b-knowledge-diffusion/), [Regulatory divergence between regions](https://onco.cc/bottlenecks/b-regulatory-fragmentation/)
- key papers: [Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update](https://onco.cc/key-papers/paper-asco-biomarkers-metastatic-breast-cancer-guideline-jco-2022/), [KEYNOTE-355: pembrolizumab plus chemotherapy for PD-L1-positive advanced triple-negative breast cancer](https://onco.cc/key-papers/paper-keynote-355-nejm-2022/), [PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer](https://onco.cc/key-papers/paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)

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