A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms.

Autor:	Owen DH; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Benner B; Division of Surgical Oncology, Department of Surgery, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Wei L; Department of Biomedical Informatics and Center for Biostatistics, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Sukrithan V; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Goyal A; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Zhou Y; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Pilcher C; Clinical Trials Office, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Suffren SA; Clinical Trials Office, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Christenson G; Clinical Trials Office, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Curtis N; Clinical Trials Office, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Jukich M; Clinical Trials Office, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Schwarz E; Division of Surgical Oncology, Department of Surgery, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Savardekar H; Division of Surgical Oncology, Department of Surgery, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Norman R; Division of Surgical Oncology, Department of Surgery, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Ferguson S; Clinical Trials Office, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Kleiber B; Clinical Trials Office, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Wesolowski R; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Carson WE; Division of Surgical Oncology, Department of Surgery, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Otterson GA; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Verschraegen CF; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Shah MH; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio., Konda B; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, Ohio.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Feb 16; Vol. 29 (4), pp. 731-741.
DOI:	10.1158/1078-0432.CCR-22-1552
Abstrakt:	Purpose: 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. Patients and Methods: 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. Results: 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. Conclusions: Combination nivolumab and temozolomide demonstrated promising activity in NEN. See related commentary by Velez and Garon, p. 691. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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