• Aditya Bardia, Sara A Hurvitz, Sara M Tolaney, Delphine Loirat, Kevin Punie, Mafalda Oliveira, Adam Brufsky, Sagar D Sardesai, Kevin Kalinsky, Amelia B Zelnak, Robert Weaver, Tiffany Traina, Florence Dalenc, Philippe Aftimos, Filipa Lynce, Sami Diab, Javier Cortés, Joyce O'Shaughnessy, Véronique Diéras, Cristiano Ferrario, Peter Schmid, Lisa A Carey, Luca Gianni, Martine J Piccart, Sibylle Loibl, David M Goldenberg, Quan Hong, Martin S Olivo, Loretta M Itri, Hope S Rugo, and ASCENT Clinical Trial Investigators.
• From 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.).
• N. Engl. J. Med. 2021 Apr 22; 384 (16): 152915411529-1541.

BackgroundPatients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker.MethodsIn this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases.ResultsA total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years; all the patients had previous use of taxanes. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001). The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P<0.001). The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment.ConclusionsProgression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan. (Funded by Immunomedics; ASCENT ClinicalTrials.gov number, NCT02574455; EudraCT number, 2017-003019-21.).Copyright © 2021 Massachusetts Medical Society.

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