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
  • 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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