Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and sa...

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Autores: Capdevila, J, Hernando, J, Teule, A, Lopez, C, Garcia-Carbonero, R, Benavent, M, Custodio, A, Garcia-Alvarez, A, Cubillo, A, Alonso, V, Carmona-Bayonas, A, Alonso-Gordoa, T, Crespo, G, Jimenez-Fonseca, P, Blanco, M, Viudez, A, La Casta, A, Sevilla, I, Segura, A, Llanos, M, Landolfi, S, Nuciforo, P, Manzano, J L, García-Carbonero, Rocio
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/23118
Acceso en línea:https://hdl.handle.net/20.500.12105/23118
Access Level:acceso abierto
Palabra clave:Neuroendocrine Tumors
Carcinoid Tumor
Humans
B7-H1 Antigen
Lung
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spelling Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung originCapdevila, JHernando, JTeule, ALopez, CGarcia-Carbonero, RBenavent, MCustodio, AGarcia-Alvarez, ACubillo, AAlonso, VCarmona-Bayonas, AAlonso-Gordoa, TCrespo, GJimenez-Fonseca, PBlanco, MViudez, ALa Casta, ASevilla, ISegura, ALlanos, MLandolfi, SNuciforo, PManzano, J LGarcía-Carbonero, RocioNeuroendocrine TumorsCarcinoid TumorHumansB7-H1 AntigenLungSingle immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.Nature Publishing GroupGrupo Espanol de Tumores Neuroendocrinos y Endocrinos (GETNE)AstraZeneca20242024-09-1620232023-05-2320232023-05-23research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttps://hdl.handle.net/20.500.12105/23118reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/231182026-06-12T12:43:37Z
dc.title.none.fl_str_mv Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
title Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
spellingShingle Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
Capdevila, J
Neuroendocrine Tumors
Carcinoid Tumor
Humans
B7-H1 Antigen
Lung
title_short Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
title_full Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
title_fullStr Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
title_full_unstemmed Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
title_sort Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
dc.creator.none.fl_str_mv Capdevila, J
Hernando, J
Teule, A
Lopez, C
Garcia-Carbonero, R
Benavent, M
Custodio, A
Garcia-Alvarez, A
Cubillo, A
Alonso, V
Carmona-Bayonas, A
Alonso-Gordoa, T
Crespo, G
Jimenez-Fonseca, P
Blanco, M
Viudez, A
La Casta, A
Sevilla, I
Segura, A
Llanos, M
Landolfi, S
Nuciforo, P
Manzano, J L
García-Carbonero, Rocio
author Capdevila, J
author_facet Capdevila, J
Hernando, J
Teule, A
Lopez, C
Garcia-Carbonero, R
Benavent, M
Custodio, A
Garcia-Alvarez, A
Cubillo, A
Alonso, V
Carmona-Bayonas, A
Alonso-Gordoa, T
Crespo, G
Jimenez-Fonseca, P
Blanco, M
Viudez, A
La Casta, A
Sevilla, I
Segura, A
Llanos, M
Landolfi, S
Nuciforo, P
Manzano, J L
García-Carbonero, Rocio
author_role author
author2 Hernando, J
Teule, A
Lopez, C
Garcia-Carbonero, R
Benavent, M
Custodio, A
Garcia-Alvarez, A
Cubillo, A
Alonso, V
Carmona-Bayonas, A
Alonso-Gordoa, T
Crespo, G
Jimenez-Fonseca, P
Blanco, M
Viudez, A
La Casta, A
Sevilla, I
Segura, A
Llanos, M
Landolfi, S
Nuciforo, P
Manzano, J L
García-Carbonero, Rocio
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
dc.contributor.none.fl_str_mv Grupo Espanol de Tumores Neuroendocrinos y Endocrinos (GETNE)
AstraZeneca
dc.subject.none.fl_str_mv Neuroendocrine Tumors
Carcinoid Tumor
Humans
B7-H1 Antigen
Lung
topic Neuroendocrine Tumors
Carcinoid Tumor
Humans
B7-H1 Antigen
Lung
description Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-05-23
2023
2023-05-23
2024
2024-09-16
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/23118
url https://hdl.handle.net/20.500.12105/23118
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
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
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
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414749795516416
score 15,811543

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