Cargando…

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

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: NCT03...

Descripción completa

Detalles Bibliográficos
Autores principales: Owen, Dwight H., Benner, Brooke, Wei, Lai, Sukrithan, Vineeth, Goyal, Ashima, Zhou, Ye, Pilcher, Carly, Suffren, Sheryl-Ann, Christenson, Gwen, Curtis, Nancy, Jukich, Megan, Schwarz, Emily, Savardekar, Himanshu, Norman, Ruthann, Ferguson, Sarah, Kleiber, Barbara, Wesolowski, Robert, Carson, William E., Otterson, Gregory A., Verschraegen, Claire F., Shah, Manisha H., Konda, Bhavana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932582/
https://www.ncbi.nlm.nih.gov/pubmed/36255391
http://dx.doi.org/10.1158/1078-0432.CCR-22-1552
_version_ 1784889485913227264
author Owen, Dwight H.
Benner, Brooke
Wei, Lai
Sukrithan, Vineeth
Goyal, Ashima
Zhou, Ye
Pilcher, Carly
Suffren, Sheryl-Ann
Christenson, Gwen
Curtis, Nancy
Jukich, Megan
Schwarz, Emily
Savardekar, Himanshu
Norman, Ruthann
Ferguson, Sarah
Kleiber, Barbara
Wesolowski, Robert
Carson, William E.
Otterson, Gregory A.
Verschraegen, Claire F.
Shah, Manisha H.
Konda, Bhavana
author_facet Owen, Dwight H.
Benner, Brooke
Wei, Lai
Sukrithan, Vineeth
Goyal, Ashima
Zhou, Ye
Pilcher, Carly
Suffren, Sheryl-Ann
Christenson, Gwen
Curtis, Nancy
Jukich, Megan
Schwarz, Emily
Savardekar, Himanshu
Norman, Ruthann
Ferguson, Sarah
Kleiber, Barbara
Wesolowski, Robert
Carson, William E.
Otterson, Gregory A.
Verschraegen, Claire F.
Shah, Manisha H.
Konda, Bhavana
author_sort Owen, Dwight H.
collection PubMed
description 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
format Online
Article
Text
id pubmed-9932582
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Association for Cancer Research
record_format MEDLINE/PubMed
spelling pubmed-99325822023-02-17 A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms Owen, Dwight H. Benner, Brooke Wei, Lai Sukrithan, Vineeth Goyal, Ashima Zhou, Ye Pilcher, Carly Suffren, Sheryl-Ann Christenson, Gwen Curtis, Nancy Jukich, Megan Schwarz, Emily Savardekar, Himanshu Norman, Ruthann Ferguson, Sarah Kleiber, Barbara Wesolowski, Robert Carson, William E. Otterson, Gregory A. Verschraegen, Claire F. Shah, Manisha H. Konda, Bhavana Clin Cancer Res Clinical Trials: Immunotherapy 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 American Association for Cancer Research 2023-02-16 2022-10-18 /pmc/articles/PMC9932582/ /pubmed/36255391 http://dx.doi.org/10.1158/1078-0432.CCR-22-1552 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
spellingShingle Clinical Trials: Immunotherapy
Owen, Dwight H.
Benner, Brooke
Wei, Lai
Sukrithan, Vineeth
Goyal, Ashima
Zhou, Ye
Pilcher, Carly
Suffren, Sheryl-Ann
Christenson, Gwen
Curtis, Nancy
Jukich, Megan
Schwarz, Emily
Savardekar, Himanshu
Norman, Ruthann
Ferguson, Sarah
Kleiber, Barbara
Wesolowski, Robert
Carson, William E.
Otterson, Gregory A.
Verschraegen, Claire F.
Shah, Manisha H.
Konda, Bhavana
A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms
title A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms
title_full A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms
title_fullStr A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms
title_full_unstemmed A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms
title_short A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms
title_sort phase ii clinical trial of nivolumab and temozolomide for neuroendocrine neoplasms
topic Clinical Trials: Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932582/
https://www.ncbi.nlm.nih.gov/pubmed/36255391
http://dx.doi.org/10.1158/1078-0432.CCR-22-1552
work_keys_str_mv AT owendwighth aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT bennerbrooke aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT weilai aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT sukrithanvineeth aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT goyalashima aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT zhouye aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT pilchercarly aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT suffrensherylann aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT christensongwen aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT curtisnancy aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT jukichmegan aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT schwarzemily aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT savardekarhimanshu aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT normanruthann aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT fergusonsarah aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT kleiberbarbara aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT wesolowskirobert aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT carsonwilliame aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT ottersongregorya aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT verschraegenclairef aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT shahmanishah aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT kondabhavana aphaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT owendwighth phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT bennerbrooke phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT weilai phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT sukrithanvineeth phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT goyalashima phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT zhouye phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT pilchercarly phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT suffrensherylann phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT christensongwen phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT curtisnancy phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT jukichmegan phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT schwarzemily phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT savardekarhimanshu phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT normanruthann phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT fergusonsarah phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT kleiberbarbara phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT wesolowskirobert phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT carsonwilliame phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT ottersongregorya phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT verschraegenclairef phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT shahmanishah phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms
AT kondabhavana phaseiiclinicaltrialofnivolumabandtemozolomideforneuroendocrineneoplasms