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

J. Capdevila (), J. Hernando, A. Teule, C. Lopez, R. Garcia-Carbonero, M. Benavent, A. Custodio, A. Garcia-Alvarez, A. Cubillo, V. Alonso, A. Carmona-Bayonas, T. Alonso-Gordoa, G. Crespo, P. Jimenez-Fonseca, M. Blanco, A. Viudez, A. Casta, I. Sevilla, A. Segura, M. Llanos, S. Landolfi, P. Nuciforo and J. L. Manzano
Additional contact information
J. Capdevila: Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VHIO)
J. Hernando: Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VHIO)
A. Teule: Institut Català d’Oncologia (ICO) - IDIBELL L’Hospitalet del Llobregat
C. Lopez: Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL
R. Garcia-Carbonero: Hospital Universitario 12 de Octubre, Imas12, UCM, CNIO
M. Benavent: University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)
A. Custodio: Hospital Universitario La Paz
A. Garcia-Alvarez: Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VHIO)
A. Cubillo: Hospital Universitario HM Sanchinarro
V. Alonso: Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISA)
A. Carmona-Bayonas: Hospital Universitario Morales Meseguer, UMU, IMIB
T. Alonso-Gordoa: Hospital Universitario Ramón y Cajal
G. Crespo: Complejo Asistencial Universitario de Burgos
P. Jimenez-Fonseca: Hospital Universitario Central de Asturias, ISPA
M. Blanco: Hospital Universitario Gregorio Marañon
A. Viudez: Hospital Universitario de Navarra
A. Casta: Hospital Universitario Donostia
I. Sevilla: Investigación Clínica y Traslacional en Cáncer/Instituto de Investigaciones Biomédicas de Málaga (IBIMA)/Hospitales Universitarios Regional y Virgen de la Victoria de Málaga
A. Segura: Hospital Universitario y Politécnico La Fe
M. Llanos: Hospital Universitario de Canarias
S. Landolfi: Vall Hebron University Hospital, CIBERONC
P. Nuciforo: Molecular Oncology Group. Vall Hebron Institute of Oncology (VHIO)
J. L. Manzano: Institut Català d’Oncologia (ICO) - Badalona, Hospital Germans Trias i Pujol

Nature Communications, 2023, vol. 14, issue 1, 1-8

Abstract: Abstract 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.

Date: 2023
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38611-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38611-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38611-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().