2. Academic Validation
  3. Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer

Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer

  • Ann Oncol. 2021 Sep;32(9):1148-1156. doi: 10.1016/j.annonc.2021.06.002.
A Bardia 1,  S M Tolaney 2,  K Punie 3,  D Loirat 4,  M Oliveira 5,  K Kalinsky 6,  A Zelnak 7,  P Aftimos 8,  F Dalenc 9,  S Sardesai 10,  E Hamilton 11,  P Sharma 12,  S Recalde 13,  E C Gil 14,  T Traina 15,  J O'Shaughnessy 16,  J Cortes 17,  M Tsai 18,  L Vahdat 19,  V Diéras 20,  L A Carey 21,  H S Rugo 22,  D M Goldenberg 23,  Q Hong 24,  M Olivo 24,  L M Itri 24,  S A Hurvitz 25
Affiliations

Affiliations

  • 1 Massachusetts General Hospital, Harvard Medical School, Boston, USA.
  • 2 Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
  • 3 Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
  • 4 Medical Oncology Department and D3i, Institut Curie, Paris, France.
  • 5 Hospital Universitari Vall d'Hebron, Barcelona, Spain.
  • 6 Columbia University Irving Medical Center, New York, USA; Winship Cancer Institute, Emory University, Atlanta, USA.
  • 7 Northside Hospital, Atlanta, USA.
  • 8 Institut Jules Bordet - Université Libre de Bruxelles, Brussels, Belgium.
  • 9 Institut Claudius Regaud, Toulouse, France.
  • 10 The Ohio State University Wexner Medical Center, Columbus, USA.
  • 11 Sarah Cannon Research Institute/Tennessee Oncology, Nashville, USA.
  • 12 University of Kansas Medical Center, Westwood, USA.
  • 13 Institut Catala d'Oncologia Hospitalet, Barcelona, Spain.
  • 14 Hospital Universitario 12 de Octubre, Madrid, Spain.
  • 15 Memorial Sloan Kettering Cancer Center, New York, USA.
  • 16 Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, USA.
  • 17 International Breast Cancer Center (IBCC), Quiron Group, Madrid & Barcelona, Spain.
  • 18 VPCI Oncology Research, Minneapolis, USA.
  • 19 MSK-Norwalk Hospital Partnership, Norwalk, USA.
  • 20 Centre Eugène Marquis, Rennes, France.
  • 21 University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, USA.
  • 22 University of California San Francisco Comprehensive Cancer Center, San Francisco, USA.
  • 23 Immunomedics, Inc., Morris Plains, USA; Center for Molecular Medicine and Immunology, Mendham, USA.
  • 24 Immunomedics, Inc., Morris Plains, USA; Department of Clinical Development, Gilead Sciences, Inc., Morris Plains, USA.
  • 25 Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, USA. Electronic address: [email protected].
PMID: 34116144 DOI: 10.1016/j.annonc.2021.06.002
Abstract

Background: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast Cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor TROP-2 expression and germline BRCA1/2 mutation status with clinical outcomes.

Patients and methods: Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine TROP-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline.

Results: Of 468 assessable patients, 290 had TROP-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low TROP-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low TROP-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations.

Conclusions: SG benefits patients with previously treated mTNBC expressing high/medium TROP-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low TROP-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.

Keywords

BRCA; triple-negative breast cancer; trophoblast cell-surface antigen 2.

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