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oai: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

00925njm 22002777a 4500 dc 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 author 2023-05-23 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. 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 Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin