Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors

Strosberg, Jonathan; El-haddad, Ghassan; Wolin, Edward; Hendifar, Andrew; Yao, James; Chasen, Beth; Mittra, Erik; Kunz, Pamela L.; Kulke, Matthew H.; Jacene, Heather; Bushnell, David; O'Dorisio, Thomas M.; Baum, Richard P.; Kulkarni, Harshad R.; Caplin, Martyn; Lebtahi, Rachida; Hobday, Timothy; Delpassand, Ebrahim; Cutsem, Eric Van; Benson, Al; Srirajaskanthan, Rajaventhan; Pavel, Marianne; Mora Salvador, Jaume; Berlin, Jordan; Grande, Enrique; Reed, Nicholas; Seregni, Ettore; Öberg, Kjell; Lopera Sierra, Maribel; Santoro, Paola; Thevenet, Thomas; Erion, Jack L.; Ruszniewski, Philippe; Kwekkeboom, Dik; Krenning, Eric; NETTER-1 Trial Investigators

Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors

BACKGROUND: Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu-177)-Dotatate in patients with ad...

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Autores:	Strosberg, Jonathan, El-haddad, Ghassan, Wolin, Edward, Hendifar, Andrew, Yao, James, Chasen, Beth, Mittra, Erik, Kunz, Pamela L., Kulke, Matthew H., Jacene, Heather, Bushnell, David, O'Dorisio, Thomas M., Baum, Richard P., Kulkarni, Harshad R., Caplin, Martyn, Lebtahi, Rachida, Hobday, Timothy, Delpassand, Ebrahim, Cutsem, Eric Van, Benson, Al, Srirajaskanthan, Rajaventhan, Pavel, Marianne, Mora Salvador, Jaume, Berlin, Jordan, Grande, Enrique, Reed, Nicholas, Seregni, Ettore, Öberg, Kjell, Lopera Sierra, Maribel, Santoro, Paola, Thevenet, Thomas, Erion, Jack L., Ruszniewski, Philippe, Kwekkeboom, Dik, Krenning, Eric, NETTER-1 Trial Investigators
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2017
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/125256
Acceso en línea:	https://hdl.handle.net/2445/125256
Access Level:	acceso abierto
Palabra clave:	Tumors Intestins Intestines

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spelling	Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine TumorsStrosberg, JonathanEl-haddad, GhassanWolin, EdwardHendifar, AndrewYao, JamesChasen, BethMittra, ErikKunz, Pamela L.Kulke, Matthew H.Jacene, HeatherBushnell, DavidO'Dorisio, Thomas M.Baum, Richard P.Kulkarni, Harshad R.Caplin, MartynLebtahi, RachidaHobday, TimothyDelpassand, EbrahimCutsem, Eric VanBenson, AlSrirajaskanthan, RajaventhanPavel, MarianneMora Salvador, JaumeBerlin, JordanGrande, EnriqueReed, NicholasSeregni, EttoreÖberg, KjellLopera Sierra, MaribelSantoro, PaolaThevenet, ThomasErion, Jack L.Ruszniewski, PhilippeKwekkeboom, DikKrenning, EricNETTER-1 Trial InvestigatorsTumorsIntestinsIntestinesBACKGROUND: Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu-177)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. METHODS: We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either Lu-177-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (Lu-177-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. RESULTS: At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the Lu-177-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the Lu-177-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the Lu-177-Dotatate group and 26 in the control group (P = 0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the Lu-177-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. CONCLUSIONS: Treatment with Lu-177-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the Lu-177-Dotatate group.Massachusetts Medical Society2018201820172018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfhttps://hdl.handle.net/2445/125256Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1056/NEJMoa1607427New England Journal of Medicine, 2017, vol. 376, num. 2, p. 125-135https://doi.org/10.1056/NEJMoa1607427(c) Massachusetts Medical Society, 2017info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1252562026-05-29T05:05:01Z
dc.title.none.fl_str_mv	Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors
title	Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors
spellingShingle	Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors Strosberg, Jonathan Tumors Intestins Intestines
title_short	Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors
title_full	Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors
title_fullStr	Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors
title_full_unstemmed	Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors
title_sort	Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors
dc.creator.none.fl_str_mv	Strosberg, Jonathan El-haddad, Ghassan Wolin, Edward Hendifar, Andrew Yao, James Chasen, Beth Mittra, Erik Kunz, Pamela L. Kulke, Matthew H. Jacene, Heather Bushnell, David O'Dorisio, Thomas M. Baum, Richard P. Kulkarni, Harshad R. Caplin, Martyn Lebtahi, Rachida Hobday, Timothy Delpassand, Ebrahim Cutsem, Eric Van Benson, Al Srirajaskanthan, Rajaventhan Pavel, Marianne Mora Salvador, Jaume Berlin, Jordan Grande, Enrique Reed, Nicholas Seregni, Ettore Öberg, Kjell Lopera Sierra, Maribel Santoro, Paola Thevenet, Thomas Erion, Jack L. Ruszniewski, Philippe Kwekkeboom, Dik Krenning, Eric NETTER-1 Trial Investigators
author	Strosberg, Jonathan
author_facet	Strosberg, Jonathan El-haddad, Ghassan Wolin, Edward Hendifar, Andrew Yao, James Chasen, Beth Mittra, Erik Kunz, Pamela L. Kulke, Matthew H. Jacene, Heather Bushnell, David O'Dorisio, Thomas M. Baum, Richard P. Kulkarni, Harshad R. Caplin, Martyn Lebtahi, Rachida Hobday, Timothy Delpassand, Ebrahim Cutsem, Eric Van Benson, Al Srirajaskanthan, Rajaventhan Pavel, Marianne Mora Salvador, Jaume Berlin, Jordan Grande, Enrique Reed, Nicholas Seregni, Ettore Öberg, Kjell Lopera Sierra, Maribel Santoro, Paola Thevenet, Thomas Erion, Jack L. Ruszniewski, Philippe Kwekkeboom, Dik Krenning, Eric NETTER-1 Trial Investigators
author_role	author
author2	El-haddad, Ghassan Wolin, Edward Hendifar, Andrew Yao, James Chasen, Beth Mittra, Erik Kunz, Pamela L. Kulke, Matthew H. Jacene, Heather Bushnell, David O'Dorisio, Thomas M. Baum, Richard P. Kulkarni, Harshad R. Caplin, Martyn Lebtahi, Rachida Hobday, Timothy Delpassand, Ebrahim Cutsem, Eric Van Benson, Al Srirajaskanthan, Rajaventhan Pavel, Marianne Mora Salvador, Jaume Berlin, Jordan Grande, Enrique Reed, Nicholas Seregni, Ettore Öberg, Kjell Lopera Sierra, Maribel Santoro, Paola Thevenet, Thomas Erion, Jack L. Ruszniewski, Philippe Kwekkeboom, Dik Krenning, Eric NETTER-1 Trial Investigators
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Tumors Intestins Intestines
topic	Tumors Intestins Intestines
description	BACKGROUND: Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu-177)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. METHODS: We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either Lu-177-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (Lu-177-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. RESULTS: At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the Lu-177-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the Lu-177-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the Lu-177-Dotatate group and 26 in the control group (P = 0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the Lu-177-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. CONCLUSIONS: Treatment with Lu-177-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the Lu-177-Dotatate group.
publishDate	2017
dc.date.none.fl_str_mv	2017 2018 2018 2018
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/125256
url	https://hdl.handle.net/2445/125256
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1056/NEJMoa1607427 New England Journal of Medicine, 2017, vol. 376, num. 2, p. 125-135 https://doi.org/10.1056/NEJMoa1607427
dc.rights.none.fl_str_mv	(c) Massachusetts Medical Society, 2017 info:eu-repo/semantics/openAccess
rights_invalid_str_mv	(c) Massachusetts Medical Society, 2017
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	11 p. application/pdf
dc.publisher.none.fl_str_mv	Massachusetts Medical Society
publisher.none.fl_str_mv	Massachusetts Medical Society
dc.source.none.fl_str_mv	Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Phase 3 Trial Of Lu-177-dotatate For Midgut Neuroendocrine Tumors

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