Phase 3 Trial of 177Lu-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 (177Lu)-Dotatate in patients with adv...

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Autores: Strosberg, Jonathan, El-Haddad, Ghassan, Wolin, Edward, Grande, Enrique, Krenning, Eric
Formato: artículo
Fecha de publicación:2017
País:España
Recursos:Universidad Francisco de Vitoria
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/3933
Acesso em linha:https://hdl.handle.net/10641/3933
Access Level:acceso abierto
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spelling Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.Strosberg, JonathanEl-Haddad, GhassanWolin, EdwardGrande, EnriqueKrenning, EricBackground: 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 (177Lu)-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 177Lu-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) (177Lu-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 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-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 177Lu-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 177Lu-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 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).20172017-01-0120172017-01-01journal articlehttp://purl.org/coar/resource_type/c_6501SMURhttp://purl.org/coar/version/c_71e4c1898caa6e32info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10641/3933reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad Francisco de VitoriaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-SinDerivadas 3.0 Españahttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/39332026-06-11T12:44:57Z
dc.title.none.fl_str_mv Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
title Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
spellingShingle Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
Strosberg, Jonathan
title_short Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
title_full Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
title_fullStr Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
title_full_unstemmed Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
title_sort Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
dc.creator.none.fl_str_mv Strosberg, Jonathan
El-Haddad, Ghassan
Wolin, Edward
Grande, Enrique
Krenning, Eric
author Strosberg, Jonathan
author_facet Strosberg, Jonathan
El-Haddad, Ghassan
Wolin, Edward
Grande, Enrique
Krenning, Eric
author_role author
author2 El-Haddad, Ghassan
Wolin, Edward
Grande, Enrique
Krenning, Eric
author2_role author
author
author
author
dc.contributor.none.fl_str_mv
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 (177Lu)-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 177Lu-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) (177Lu-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 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-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 177Lu-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 177Lu-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 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
SMUR
http://purl.org/coar/version/c_71e4c1898caa6e32
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10641/3933
url https://hdl.handle.net/10641/3933
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-SinDerivadas 3.0 España
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-SinDerivadas 3.0 España
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
instname:Universidad Francisco de Vitoria
instname_str Universidad Francisco de Vitoria
reponame_str DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
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