# PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer

Source: https://onco.cc/key-papers/paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021/  
OnCo record `paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Three different PD-L1 tests run on the same 614 IMpassion130 tumours called 46, 75 and 73 percent of them positive and agreed with each other only about 69 percent of the time; the benefit of atezolizumab was concentrated in the tumours all three called positive.

## Summary

Rugo, Loi, Adams, Schmid and colleagues centrally tested samples from 614 patients (68.1 percent of the IMpassion130 population) for PD-L1 on immune cells by VENTANA SP142, SP263 and Dako 22C3, and as 22C3 combined positive score. Prevalence of immune cell PD-L1 of 1 percent or more was 46.4 percent (SP142), 74.9 percent (SP263) and 73.1 percent (22C3); 80.9 percent had 22C3 combined positive score of 1 or more. Analytical concordance of SP263 and 22C3 with SP142 was 69.2 and 68.7 percent; almost all SP142-positive cases were positive on the others, but 29.6 percent of SP263-positive and 29.0 percent of 22C3-positive cases were SP142-negative. Atezolizumab benefit in SP263- and 22C3-positive patients (progression-free survival hazard ratios 0.64 to 0.68; overall survival 0.75 to 0.79) was driven by double-positive cases (0.60 to 0.61; 0.71 to 0.75) rather than single-positive cases (0.68 to 0.81; 0.87 to 0.95). Harmonised cut-offs (SP263 immune cells 4 percent or more; 22C3 combined positive score 10 or more) reached only about 75 percent concordance with SP142.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: Journal of the National Cancer Institute
- Year: 2021
- DOI: 10.1093/jnci/djab108
- Authors: Rugo HS, Loi S, Adams S, et al.
- Findings: PD-L1 positivity (immune cells 1 percent or more): SP142 46.4 percent, SP263 74.9 percent, 22C3 73.1 percent; 22C3 combined positive score 1 or more 80.9 percent.; Concordance with SP142: SP263 69.2 percent, 22C3 68.7 percent; harmonised cut-offs about 75 percent.; Benefit concentrated in double-positive cases; single-positive cases showed overall survival hazard ratios of 0.87 to 0.95.
- What it means: The clearest demonstration that PD-L1 positive in triple-negative breast cancer means different things depending on the kit; with atezolizumab withdrawn, pembrolizumab's 22C3 combined positive score of 10 is the surviving standard, and roughly a quarter of patients get a different answer depending on which assay their laboratory runs.
- Caveats: Retrospective, in 68 percent of the trial population.; Atezolizumab's breast cancer indication has since been withdrawn in the United States, so the clinical anchor is historical.

## Sources

- J Natl Cancer Inst 2021: https://doi.org/10.1093/jnci/djab108
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34097070/
- ClinicalTrials.gov NCT02425891: https://clinicaltrials.gov/study/NCT02425891

## Connected records

- biomarkers: [PD-L1 CPS (combined positive score)](https://onco.cc/biomarkers/pd-l1-cps/), [PD-L1 IC score (immune-cell score, SP142)](https://onco.cc/biomarkers/pd-l1-ic-score/)
- cancers: [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Nab-paclitaxel](https://onco.cc/drugs/nab-paclitaxel/), [PD-L1 IHC 22C3 pharmDx](https://onco.cc/drugs/dako-pd-l1-22c3-pharmdx/), [VENTANA PD-L1 (SP142) Assay](https://onco.cc/drugs/ventana-pd-l1-sp142/), [VENTANA PD-L1 (SP263) Assay](https://onco.cc/drugs/ventana-pd-l1-sp263/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [Combined positive score (CPS)](https://onco.cc/terms/cps/), [Hazard ratio (HR)](https://onco.cc/terms/hazard-ratio/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [PD-L1 assay discordance (SP142, SP263 and 22C3 in breast cancer)](https://onco.cc/terms/pd-l1-assay-discordance/)
- trials: [IMpassion130](https://onco.cc/trials/impassion130/), [KEYNOTE-355](https://onco.cc/trials/keynote-355/)
- people: [Eric P. Winer](https://onco.cc/people/eric-winer/), [Hope S. Rugo](https://onco.cc/people/hope-rugo/), [Peter Schmid](https://onco.cc/people/peter-schmid/), [Sherene Loi](https://onco.cc/people/loi-sherene/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Regulatory divergence between regions](https://onco.cc/bottlenecks/b-regulatory-fragmentation/)
- journals: [JNCI: Journal of the National Cancer Institute](https://onco.cc/journals/jnci/)
- 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/)
- ideas: [Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance](https://onco.cc/ideas/idea-tnbc-pd-l1-assay-harmonisation/)

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