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Publications

Journal Article Randomized Controlled Trial Clinical Trial, Phase III Multicenter Study Ppublish

PubMed: 40467898 DOI: 10.1038/s41591-025-03725-4

Peri-operative atezolizumab in early-stage triple-negative breast cancer: final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial.

Nat Med 31(7):2397-2404

Authors: Elizabeth A Mittendorf, Zoe June Assaf, Nadia Harbeck, Hong Zhang, Shigehira Saji, Kyung Hae Jung, Roberto Hegg, Andreas Koehler, Joohyuk Sohn, Hiroji Iwata, Melinda L Telli, Cristiano Ferrario, Kevin Punie, Aditi Qamra, Max Dieterich, Yun Xu, Mario Liste-Hermoso, Esther Shearer-Kang, Luciana Molinero, Stephen Y Chui, Carlos H Barrios

Affiliations

  • Department of Surgery, Division of Breast Surgery, Brigham and Women's Hospital, Boston, MA, USA.
  • Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
  • Oncology Biomarker Development, Genentech, South San Francisco, CA, USA.
  • Department of Gynecology and Obstetrics and Comprehensive Cancer Center Munich, Breast Center, Ludwig-Maximilians-University Hospital, Munich, Germany.
  • Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Fukushima Medical University, Fukushima, Japan.
  • Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • University of São Paulo, São Paulo, Brazil.
  • Pérola Centro de Pesquisa em Oncologia, São Paulo, Brazil.
  • Gemeinschaftspraxis für Haematologie und Onkologie Langen, Langen, Germany.
  • Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea.
  • Aichi Cancer Center Hospital, Nagoya, Japan.
  • Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Jewish General Hospital-McGill University, Montréal, Quebec, Canada.
  • Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
  • Data and Statistical Sciences-Oncology, Hoffmann-La Roche Limited, Mississauga, Ontario, Canada.
  • Product Development Oncology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Product Development Safety, Genentech, South San Francisco, CA, USA.
  • Product Development Oncology, Genentech, South San Francisco, CA, USA.
  • Latin American Cooperative Oncology Group (LACOG), Oncoclínicas, Porto Alegre, Brazil.

Abstract

Previously published results demonstrated that the randomized phase 3 IMpassion031 trial met its primary objective: adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate in patients with stage II/III triple-negative breast cancer (TNBC). Here we report the prespecified final analysis of the secondary endpoints with 3 years' follow-up, together with exploratory analyses of circulating tumor (ct)DNA. Patients with previously untreated stage II/III TNBC enrolled in 75 academic and community sites in 13 countries were randomized 1:1 to receive neoadjuvant chemotherapy with either peri-operative atezolizumab (n = 165) or preoperative placebo (n = 168). Descriptive secondary endpoints included event-free, disease-free and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival hazard ratio (HR), 0.76; 95% confidence interval (CI), 0.47-1.21; disease-free survival HR, 0.76; 95% CI, 0.44-1.30; overall survival HR, 0.56; 95% CI, 0.30-1.04). Among patients without pCR, 14 of 70 (20%) atezolizumab-treated and 33 of 99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory biomarker analyses, patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. These data show that adding atezolizumab to chemotherapy for stage II/III TNBC is associated with favorable long-term outcomes, and ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935 .

MeSH

Triple Negative Breast Neoplasms, Disease-Free Survival, Breast Neoplasms, Molecular Biology, Neoplasms, Drug Therapy, Breast, Therapeutics, Chemotherapy

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