Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial
Year: 2026
Type: article
Study design: Clinical Trial
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 .
Source: Nature Medicine
Authors: 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
Institutions: Goethe University Frankfurt, University of Pittsburgh, NRG Oncology, German Breast Group, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, NSABP Foundation, Kliniken Essen-Mitte, University Medical Centre Mannheim, Allegheny Health Network, German Cancer Research Center, University Hospital Heidelberg, National Center for Tumor Diseases, Sana Klinikum Offenbach, Magee-Womens Hospital, Genentech, Hospital Clínico San Carlos, GEICAM – Spanish Breast Cancer Group, Compass Oncology, Comprehensive Cancer Centers of Nevada, Hospital Universitari Arnau de Vilanova, Instituto de Investigación Biomédica de Lleida, Universität Ulm, Kantonsspital St. Gallen, Jewish General Hospital, McGill University, Hospital General Universitario de Elche, Hôpital du Saint-Sacrement, Aurora Health Care, Universitätsklinikum Gießen und Marburg, Roche (Portugal), AdventHealth Orlando, AdventHealth
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7204874960