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Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.
Aditya Bardia1, Sara A Hurvitz1, Sara M Tolaney1
1From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana-Farber Cancer Institute (S.M.T.) - both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) - all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet-Université Libre de Bruxelles (M.J.P.), Brussels - all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) - all in Barcelona; Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) - both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.).
Sacituzumab govitecan significantly improved progression-free and overall survival in patients with metastatic triple-negative breast cancer compared to chemotherapy. While effective, it was associated with increased risks of neutropenia and diarrhea.
Area of Science:
- Oncology
- Pharmacology
Background:
- Metastatic triple-negative breast cancer (mTNBC) presents a significant clinical challenge with limited treatment options.
- Human trophoblast cell-surface antigen 2 (Trop-2) is a transmembrane glycoprotein overexpressed in most breast cancers, making it a viable therapeutic target.
Purpose of the Study:
- To evaluate the efficacy and safety of sacituzumab govitecan compared to physician's choice of single-agent chemotherapy in patients with relapsed or refractory mTNBC.
Main Methods:
- A randomized, phase 3 trial (ASCENT) involving 468 patients without brain metastases.
- Patients received either sacituzumab govitecan or chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine).
- Primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Main Results:
- Sacituzumab govitecan demonstrated significantly longer median PFS (5.6 months vs. 1.7 months) and overall survival (12.1 months vs. 6.7 months) compared to chemotherapy.
- Objective response rates were higher with sacituzumab govitecan (35% vs. 5%).
- Grade 3 or higher adverse events included neutropenia (51% vs. 33%) and diarrhea (10% vs. <1%).
Conclusions:
- Sacituzumab govitecan offers a substantial survival benefit for patients with mTNBC over standard chemotherapy.
- Increased incidence of myelosuppression and diarrhea are key safety considerations for sacituzumab govitecan treatment.
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