Loading
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.
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.
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that PD-L1 positive in triple-negative breast cancer means different things depending on the kit; with atezolizumab withdrawn, pembrolizumab's 22C3 combined positive score of 10 is the surviving standard, and roughly a quarter of patients get a different answer depending on which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.
Shares Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance, Combined positive score (CPS), Biomarkers are not validated or standardised, PD-L1 and the tag tnbc-evidence.
Shares JNCI: Journal of the National Cancer Institute, Immunohistochemistry (IHC), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Immunohistochemistry (IHC), Biomarkers are not validated or standardised, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Hazard ratio (HR), Biomarkers are not validated or standardised, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Hazard ratio (HR), Biomarkers are not validated or standardised, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Immunohistochemistry (IHC), Biomarkers are not validated or standardised, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Hazard ratio (HR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares JNCI: Journal of the National Cancer Institute, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.