PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab plus nab-Paclitaxel–Treated Advanced Triple-Negative Breast Cancer
Menée à partir d'échantillons tumoraux prélevés sur 614 patientes atteintes d'un cancer du sein triple négatif de stade avancé et incluses dans un essai de phase III évaluant l'atézolizumab en combinaison avec le nab-paclitaxel, cette étude analyse la concordance des résultats de trois tests immunohistochimiques destinés à déterminer le statut PD-L1 des cellules tumorales et des cellules immunitaires ayant infiltré la tumeur
Background : In the Phase III IMpassion130 study, atezolizumab plus nab-paclitaxel (A+nP) showed clinical benefit in advanced/metastatic triple-negative breast cancer (TNBC) patients who were programmed death-ligand 1 (PD-L1) + (tumor-infiltrating immune cells [IC] ≥1%) using the SP142 immunohistochemistry (IHC) assay. Here we evaluate 2 other PD-L1 assays for analytical concordance with SP142 and patient-associated clinical outcomes.
Methods : Samples from 614 patients (68.1% of intention-to-treat population) were centrally evaluated by IHC for PD-L1 status on IC (VENTANA SP142, SP263, Dako 22C3) or as a combined positive score (CPS; 22C3).
Results : Using SP142, SP263, and 22C3 assays, PD-L1 IC ≥ 1% prevalence was 46.4% (95% confidence interval [CI] = 42.5–50.4%), 74.9% (95% CI = 71.5–78.3%), and 73.1% (95% CI = 69.6–76.6%), respectively; 80.9% were 22C3 at CPS ≥1. At IC ≥ 1% (+), the analytical concordance between SP142 and SP263 and 22C3 was 69.2% and 68.7%, respectively. Almost all SP142+ cases were captured by other assays (double positive), but several SP263 + (29.6%) or 22C3 + (29.0%) cases were SP142– (single positive). A+nP clinical activity vs placebo+nP in SP263+ and 22C3+ patients (progression-free survival [PFS] hazard ratios [HRs] = 0.64–0.68; overall survival [OS] HRs = 0.75–0.79) was driven by double-positive (PFS HRs = 0.60–0.61; OS HRs = 0.71–0.75) rather than single-positive cases (PFS HRs = 0.68–0.81; OS HRs = 0.87–0.95). Concordance for harmonized cutoffs for SP263 (IC ≥ 4%) and 22C3 (CPS ≥10) to SP142 IC ≥ 1% was subpar (approximately 75%).
Conclusions : 22C3 and SP263 assays identified more patients as PD-L1 + (IC ≥ 1%) than SP142. No inter-assay analytical equivalency was observed. Consistent improved A+nP efficacy was captured by the SP142 PD-L1 IC ≥ 1% subgroup nested within 22C3 and SP263 PD-L1 + (IC ≥ 1%) populations.
Journal of the National Cancer Institute , article en libre accès, 2020