2026-04-30T08:52:24Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/231182024-11-28T15:06:16Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19597col_20.500.12105_16938col_20.500.12105_16927col_20.500.12105_16958col_20.500.12105_16962col_20.500.12105_16970col_20.500.12105_16973col_20.500.12105_16981col_20.500.12105_16987col_20.500.12105_16990
Repisalud
author
Capdevila, J
author
Hernando, J
author
Teule, A
author
Lopez, C
author
Garcia-Carbonero, R
author
Benavent, M
author
Custodio, A
author
Garcia-Alvarez, A
author
Cubillo, A
author
Alonso, V
author
Carmona-Bayonas, A
author
Alonso-Gordoa, T
author
Crespo, G
author
Jimenez-Fonseca, P
author
Blanco, M
author
Viudez, A
author
La Casta, A
author
Sevilla, I
author
Segura, A
author
Llanos, M
author
Landolfi, S
author
Nuciforo, P
author
Manzano, J L
author
García-Carbonero, Rocio
funder
Grupo Espanol de Tumores Neuroendocrinos y Endocrinos (GETNE)
funder
AstraZeneca
2024-09-16T08:17:11Z
2024-09-16T08:17:11Z
2023-05-23
Nat Commun . 2023 ;14(1):2973.
10.1038/s41467-023-38611-5
2041-1723
Nature communications
37221181
https://hdl.handle.net/20.500.12105/23118
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.
eng
Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin
research article