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

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Journal
Nature Medicine
Published
2026-09-01
DOI
https://doi.org/10.1038/s41591-026-04565-6
Primary Topic
Breast Cancer Treatment Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Sabine Seiler, Julia Teply‐Szymanski, Stephani Christensen, P. Sivaramakrishna Rachakonda et al.
Nature Medicine
Breast Cancer Treatment Studies
article

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

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

Abstract

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 .

Nature Medicine
Goethe University Frankfurt (DE), Aurora Health Care (US), Allegheny Health Network (US), Philipps University of Marburg (DE), Sarah Cannon Research Institute (GB), University of Mannheim (DE), Universität Ulm (DE), University of St.Gallen (CH), Heidelberg University (DE), Universitätsklinikum Gießen und Marburg (DE), Jewish General Hospital (CA), Hospital Universitari Arnau de Vilanova (ES), University Hospital Heidelberg (DE), Hospital Clínico San Carlos (ES), Florida Hospital Cancer Institute (US), Hôpital du Saint-Sacrement (CA), Compass Oncology (US), Sarah Cannon (US), Magee-Womens Hospital (US), National Center for Tumor Diseases (DE), Hospital General Universitario de Elche (ES), UPMC Hillman Cancer Center (US), German Breast group (DE), Colorado Permanente Medical Group (US), University Hospital Frankfurt (DE), Sana Klinikum Offenbach (DE), Roche (Portugal) (PT), Kliniken Essen-Mitte (DE), Frankfurt Cancer Institute (DE), NRG Oncology (US), NSABP Foundation (US), GEICAM – Spanish Breast Cancer Group (ES), Comprehensive Cancer Centers of Nevada (US), McGill University (CA)
European Commission, Goethe-Universität Frankfurt am Main, Hector Stiftung, Genentech, Horizon 2020 Framework Programme
Good health and well-being
Openalex Percentile: Top 15%
Breast Cancer Treatment Studies
DOIOpen Access PDFOpenAlex
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