{"entity":{"id":"paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021","kind":"paper","name":"PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer","aka":[],"tldr":"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.","asOf":"2026-09-24","links":[{"label":"J Natl Cancer Inst 2021","url":"https://doi.org/10.1093/jnci/djab108"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34097070/"},{"label":"ClinicalTrials.gov NCT02425891","url":"https://clinicaltrials.gov/study/NCT02425891"}],"tags":["tnbc-evidence"],"related":["pd-l1-ic-score","pd-l1-cps"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pdl1"],"drugs":["atezolizumab","nab-paclitaxel","ventana-pd-l1-sp142","ventana-pd-l1-sp263","dako-pd-l1-22c3-pharmdx"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["cps","ihc","hazard-ratio"],"trials":["impassion130","keynote-355"],"people":["hope-rugo","peter-schmid","loi-sherene","eric-winer"],"bottlenecks":["b-biomarker-validation","b-regulatory-fragmentation"],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"Journal of the National Cancer Institute","year":2021,"doi":"10.1093/jnci/djab108","pmid":"34097070","authors":"Rugo HS, Loi S, Adams S, et al.","paperType":"translational","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."],"whatItMeans":"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."],"changedPractice":false,"participants":614},"route":"/key-papers/paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021/","neighbours":{"biomarker":[{"id":"pd-l1-cps","kind":"biomarker","name":"PD-L1 CPS (combined positive score)","route":"/biomarkers/pd-l1-cps/"},{"id":"pd-l1-ic-score","kind":"biomarker","name":"PD-L1 IC score (immune-cell score, SP142)","route":"/biomarkers/pd-l1-ic-score/"}],"cancer":[{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nab-paclitaxel","kind":"drug","name":"Nab-paclitaxel","route":"/drugs/nab-paclitaxel/"},{"id":"dako-pd-l1-22c3-pharmdx","kind":"drug","name":"PD-L1 IHC 22C3 pharmDx","route":"/drugs/dako-pd-l1-22c3-pharmdx/"},{"id":"ventana-pd-l1-sp142","kind":"drug","name":"VENTANA PD-L1 (SP142) Assay","route":"/drugs/ventana-pd-l1-sp142/"},{"id":"ventana-pd-l1-sp263","kind":"drug","name":"VENTANA PD-L1 (SP263) Assay","route":"/drugs/ventana-pd-l1-sp263/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"},{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"pd-l1-assay-discordance","kind":"term","name":"PD-L1 assay discordance (SP142, SP263 and 22C3 in breast cancer)","route":"/terms/pd-l1-assay-discordance/"}],"trial":[{"id":"impassion130","kind":"trial","name":"IMpassion130","route":"/trials/impassion130/"},{"id":"keynote-355","kind":"trial","name":"KEYNOTE-355","route":"/trials/keynote-355/"}],"person":[{"id":"eric-winer","kind":"person","name":"Eric P. Winer","route":"/people/eric-winer/"},{"id":"hope-rugo","kind":"person","name":"Hope S. Rugo","route":"/people/hope-rugo/"},{"id":"peter-schmid","kind":"person","name":"Peter Schmid","route":"/people/peter-schmid/"},{"id":"loi-sherene","kind":"person","name":"Sherene Loi","route":"/people/loi-sherene/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-regulatory-fragmentation","kind":"bottleneck","name":"Regulatory divergence between regions","route":"/bottlenecks/b-regulatory-fragmentation/"}],"journal":[{"id":"jnci","kind":"journal","name":"JNCI: Journal of the National Cancer Institute","route":"/journals/jnci/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"idea":[{"id":"idea-tnbc-pd-l1-assay-harmonisation","kind":"idea","name":"Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance","route":"/ideas/idea-tnbc-pd-l1-assay-harmonisation/"}]}}