Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ adverse effects
Antigens, Neoplasm
Antineoplastic Agents
/ adverse effects
Camptothecin
/ adverse effects
Cell Adhesion Molecules
/ antagonists & inhibitors
Drug Resistance, Neoplasm
Female
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Immunoconjugates
/ adverse effects
Male
Middle Aged
Neoplasm Recurrence, Local
/ drug therapy
Progression-Free Survival
Survival Analysis
Triple Negative Breast Neoplasms
/ drug therapy
Tumor Burden
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
22 04 2021
22 04 2021
Historique:
entrez:
21
4
2021
pubmed:
22
4
2021
medline:
28
4
2021
Statut:
ppublish
Résumé
Patients 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. In 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. A 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. Progression-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.).
Sections du résumé
BACKGROUND
Patients 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.
METHODS
In 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.
RESULTS
A 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.
CONCLUSIONS
Progression-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.).
Identifiants
pubmed: 33882206
doi: 10.1056/NEJMoa2028485
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antigens, Neoplasm
0
Antineoplastic Agents
0
Cell Adhesion Molecules
0
Immune Checkpoint Inhibitors
0
Immunoconjugates
0
TACSTD2 protein, human
0
sacituzumab govitecan
M9BYU8XDQ6
Camptothecin
XT3Z54Z28A
Banques de données
ClinicalTrials.gov
['NCT02574455']
EudraCT
['2017-003019-21']
Types de publication
Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1529-1541Investigateurs
Foluso Ademuyiwa
(F)
Philippe Aftimos
(P)
Anne Armstrong
(A)
Aditya Bardia
(A)
Frédéric Bigot
(F)
Adam Brufsky
(A)
Lourdes Calvo Martînez
(L)
Lisa A Carey
(LA)
Eva Ciruelos Gil
(E)
Alison Conlin
(A)
Javier Cortés
(J)
Florence Dalenc
(F)
Brooke Daniel
(B)
Michael Danso
(M)
Jorge Darcourt
(J)
Sami Diab
(S)
Jennifer Diamond
(J)
Véronique Diéras
(V)
Anne Favret
(A)
Mariía Fernaández Abad
(M)
Cristiano Ferrario
(C)
Nelly Firmin
(N)
Christel Fontaine
(C)
Jean-Sebastien Frenel
(JS)
Luca Gianni
(L)
Stephanie Graff
(S)
Erika Hamilton
(E)
Eric Harris
(E)
Lowell Hart
(L)
Susanna Hegewisch-
(S)
Becker Becker
(B)
Stéphanie Henry
(S)
Christie Hilton
(C)
Sara A Hurvitz
(SA)
Sharad Jain
(S)
Kevin Kalinsky
(K)
Pinelopi Kechagioglou
(P)
Leonard Klein
(L)
Roberto Leon-Ferre
(R)
Florence Lerebours
(F)
Sibylle Loibl
(S)
Delphine Loirat
(D)
Rafael López
(R)
Filipa Lynce
(F)
Zulfiqar Malik
(Z)
Laura Mansi
(L)
María Martínez García
(M)
Ingrid Mayer
(I)
Michael Meshad
(M)
Judith Meza-Junco
(J)
Rebecca Moroose
(R)
Rita Nanda
(R)
Petros Nikolinakos
(P)
Joyce O'Shaughnessy
(J)
Mafalda Oliveira
(M)
Coral Omene
(C)
Felicity Paterson
(F)
Alejandra Perez
(A)
José Manuel Perez Garcia
(JM)
Martine Piccart
(M)
Kevin Punie
(K)
Daniel Rayson
(D)
Sabela Recalde
(S)
Donald Richards
(D)
Paul Richards
(P)
Hope Rugo
(H)
Manuel Ruiz-Borrego
(M)
Mahasti Saghatchian
(M)
Sagar R Sardesai
(SR)
Peter Schmid
(P)
Lowell Schnipper
(L)
Lee Schwartzberg
(L)
Priyanka Sharma
(P)
Amna Sheri
(A)
Saiqa Spensley
(S)
Christopher Stokoe
(C)
Jun Sun
(J)
Karen Tedesco
(K)
Sara M Tolaney
(SM)
Tiffany Traina
(T)
Olivier Tredan
(O)
Michaela Tsai
(M)
Linda Vahdat
(L)
Tanya Wahl
(T)
Grace Wang
(G)
Robert Weaver
(R)
Rudolf Weide
(R)
Robyn Young
(R)
Amelia Zelnak
(A)
Commentaires et corrections
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Informations de copyright
Copyright © 2021 Massachusetts Medical Society.