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Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial

Sibylle Loibl, Gong Tang, Valentina Nekljudova, Priya Rastogi, Sivaramakrishna Rachakonda, Mattea Reinisch, Joshua Acosta, Andreas Schneeweiss, Christie Hilton, Sabine Seiler, Rohit Bhargava, Thomas Karn, Patricia Cortazar, Fernando Moreno, Jay Andersen, Stephani Christensen, Peter Klare, Sujatha Murali, Serafín Morales, Jens Huober, Jean-François Boileau, Álvaro Rodríguez-Lescure, Dominique Boudreau, Peter J. Polewski, Julia Teply-Szymanski, João Mouta, Eleftherios P. Mamounas, Carsten Denkert, Norman Wolmark, Charles E. Geyer

Nature Medicine · 2026

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype with an activated tumor immune microenvironment. The multicenter, multinational, double-blinded NSABP B-59/GeparDouze trial evaluated the addition of atezolizumab (atezo) (773 patients randomized) or placebo (777 patients) to sequential taxane–carboplatin–anthracycline-based neoadjuvant chemotherapy in stage II–III TNBC. The addition of atezo did not significantly improve the primary endpoint of event-free survival (EFS) (HR, 0.80 (95% CI, 0.062–1.03); stratified log-rank P = 0.083, 4-year EFS rates difference 3.3%). The HR for overall survival was 0.86 (95% CI, 0.62–1.19), with a 4-year benefit of 0.7%. Prespecified subgroup analyses suggested heterogeneity in EFS, with benefit of atezo in patients presenting with clinical lymph node involvement ( P interaction = 0.039). Treatment-emergent adverse events with grades ≥3 were reported in 75.3% (atezo) versus 73.4% (placebo), and immune-related adverse events were reported in 27.6% (atezo) versus 11.4% (placebo). A total of 196 (25.5%) patients discontinued atezo and 143 (18.8%) patients discontinued placebo in the neoadjuvant phase. In an exploratory mRNA-based subset analysis, patients with basal-like immune-activated tumors may have benefited from atezo. TNBC subtyping to identify basal-like immune-activated tumors and quantification of tumor-infiltrating lymphocytes to identify tumors with high tumor-infiltrating lymphocyte counts could be a promising strategy to identify patients who benefit from the addition of immune checkpoint inhibitors to neoadjuvant chemotherapy. ClinicalTrials.gov registration: NCT03281954 .

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Autor:innen
Sibylle Loibl, Gong Tang, Valentina Nekljudova, Priya Rastogi, Sivaramakrishna Rachakonda, Mattea Reinisch, Joshua Acosta, Andreas Schneeweiss, Christie Hilton, Sabine Seiler, Rohit Bhargava, Thomas Karn, Patricia Cortazar, Fernando Moreno, Jay Andersen, Stephani Christensen, Peter Klare, Sujatha Murali, Serafín Morales, Jens Huober, Jean-François Boileau, Álvaro Rodríguez-Lescure, Dominique Boudreau, Peter J. Polewski, Julia Teply-Szymanski, João Mouta, Eleftherios P. Mamounas, Carsten Denkert, Norman Wolmark, Charles E. Geyer
Quelle
Nature Medicine
Publikation
2026-01-01
Band / Ausgabe
Nicht angegeben
Seiten
Nicht angegeben
ISSN / ISBN
1078-8956, 1546-170X
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Sibylle Loibl, Gong Tang, Valentina Nekljudova, Priya Rastogi, Sivaramakrishna Rachakonda, Mattea Reinisch, Joshua Acosta, Andreas Schneeweiss, Christie Hilton, Sabine Seiler, Rohit Bhargava, Thomas Karn, Patricia Cortazar, Fernando Moreno, Jay Andersen, Stephani Christensen, Peter Klare, Sujatha Murali, Serafín Morales, Jens Huober, Jean-François Boileau, Álvaro Rodríguez-Lescure, Dominique Boudreau, Peter J. Polewski, Julia Teply-Szymanski, João Mouta, Eleftherios P. Mamounas, Carsten Denkert, Norman Wolmark, Charles E. Geyer (2026). Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial. Nature Medicine. https://doi.org/10.1038/s41591-026-04565-6
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