Hope S Rugo1, Sherene Loi2, Sylvia Adams3, Peter Schmid4, Andreas Schneeweiss5, Carlos H Barrios6, Hiroji Iwata7, Véronique Diéras8, Eric P Winer9, Mark M Kockx10, Dieter Peeters10, Stephen Y Chui11, Jennifer C Lin11, Anh Nguyen Duc12, Giuseppe Viale13, Luciana Molinero11, Leisha A Emens14. 1. University of California San Francisco Comprehensive Cancer Center, San Francisco, CA. 2. Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC, Australia. 3. New York University Langone Health, Perlmutter Cancer Center, New York, NY. 4. Barts Cancer Institute, Queen Mary University of London, London, UK. 5. National Center for Tumor Diseases (NCT), Heidelberg University Hospital and German Cancer Research Center, Heidelberg, Germany. 6. Centro de Pesquisa Clínica, HSL, PUCRS, Porto Alegre, Brazil. 7. Aichi Cancer Center Hospital, Nagoya, Japan. 8. Department of Medical Oncology, Institut Curie, Paris, and Centre Eugène Marquis, Rennes, France. 9. Dana-Farber Cancer Institute, Boston, MA. 10. CellCarta NV,a Antwerp, Belgium. 11. Genentech, Inc., South San Francisco, CA. 12. Roche, Basel, Switzerland. 13. University of Milan, Milan, Italy, and European Institute of Oncology IRCCS, Milan, Italy. 14. University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA.
Abstract
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.
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 SP142PD-L1 IC ≥ 1% subgroup nested within 22C3 and SP263PD-L1 + (IC ≥ 1%) populations.