A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
16 02 2023
16 02 2023
Historique:
received:
17
06
2022
revised:
25
08
2022
accepted:
13
10
2022
pubmed:
19
10
2022
medline:
18
2
2023
entrez:
18
10
2022
Statut:
ppublish
Résumé
Treatment options are limited in patients with metastatic neuroendocrine neoplasms (NEN). We present the results for a phase II trial of combination nivolumab and temozolomide in patients with advanced NEN along with results of immune changes in peripheral blood. NCT03728361 is a nonrandomized, phase II study of nivolumab and temozolomide in patients with NEN. The primary endpoint was response rate using RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Immune profiling was performed by mass cytometry to evaluate the effect on peripheral blood immune cell subsets. Among all 28 patients with NEN, the confirmed response rate was 9/28 [32.1%, 95% confidence interval (CI): 15.9-52.4]. Of 11 patients with lung NEN, the response rate was 64% (n = 7); there was a significant difference in responses by primary tumor location (lung vs. others, P = 0.020). The median PFS was 8.8 months (95% CI: 3.9-11.1 months), and median OS was 32.3 months (95% CI: 20.7-not reached months). Exploratory blood immune cell profiling revealed an increase in circulating CD8+ T cells (27.9% ± 13.4% vs. 31.7% ± 14.6%, P = 0.03) and a decrease in CD4+ T cells (59.6% ± 13.1% vs. 56.5% ± 13.0%, P = 0.001) after 2 weeks of treatment. LAG-3-expressing total T cells were lower in patients experiencing a partial response (0.18% ± 0.24% vs. 0.83% ± 0.55%, P = 0.028). Myeloid-derived suppressor cell levels increased during the study and did not correlate with response. Combination nivolumab and temozolomide demonstrated promising activity in NEN. See related commentary by Velez and Garon, p. 691.
Identifiants
pubmed: 36255391
pii: 709808
doi: 10.1158/1078-0432.CCR-22-1552
pmc: PMC9932582
mid: NIHMS1844897
doi:
Substances chimiques
Nivolumab
31YO63LBSN
Temozolomide
YF1K15M17Y
Types de publication
Editorial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Comment
Langues
eng
Sous-ensembles de citation
IM
Pagination
731-741Subventions
Organisme : NCI NIH HHS
ID : K12 CA133250
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Commentaires et corrections
Type : CommentOn
Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
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