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Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial
BACKGROUND: We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC). METHODS: In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received av...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198369/ https://www.ncbi.nlm.nih.gov/pubmed/30348224 http://dx.doi.org/10.1186/s40425-018-0424-9 |
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author | Le Tourneau, Christophe Hoimes, Christopher Zarwan, Corrine Wong, Deborah J. Bauer, Sebastian Claus, Rainer Wermke, Martin Hariharan, Subramanian von Heydebreck, Anja Kasturi, Vijay Chand, Vikram Gulley, James L. |
author_facet | Le Tourneau, Christophe Hoimes, Christopher Zarwan, Corrine Wong, Deborah J. Bauer, Sebastian Claus, Rainer Wermke, Martin Hariharan, Subramanian von Heydebreck, Anja Kasturi, Vijay Chand, Vikram Gulley, James L. |
author_sort | Le Tourneau, Christophe |
collection | PubMed |
description | BACKGROUND: We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC). METHODS: In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received avelumab at 10 mg/kg intravenously every 2 weeks. Continuation of mitotane was permitted; however, mitotane levels during the study were not recorded. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors v1.1. RESULTS: Fifty patients received avelumab and were followed for a median of 16.5 months. Prior treatment included ≥2 lines in 74.0%; mitotane was continued in 50.0%. The objective response rate (ORR) was 6.0% (95% CI, 1.3% to 16.5%; partial response in 3 patients). Twenty-one patients (42.0%) had stable disease as best response (disease control rate, 48.0%). Median progression-free survival was 2.6 months (95% CI, 1.4 to 4.0), median overall survival (OS) was 10.6 months (95% CI, 7.4 to 15.0), and the 1-year OS rate was 43.4% (95% CI, 27.9% to 57.9%). In evaluable patients with PD-L1+ (n = 12) or PD-L1− (n = 30) tumors (≥5% tumor cell cutoff), ORR was 16.7% vs 3.3% (P = .192). Treatment-related adverse events (TRAEs) occurred in 82.0%; the most common were nausea (20.0%), fatigue (18.0%), hypothyroidism (14.0%), and pyrexia (14.0%). Grade 3 TRAEs occurred in 16.0%; no grade 4 to 5 TRAEs occurred. Twelve patients (24.0%) had an immune-related TRAE of any grade, which were grade 3 in 2 patients (4.0%): adrenal insufficiency (n = 1), and pneumonitis (n = 1). CONCLUSIONS: Avelumab showed clinical activity and a manageable safety profile in patients with platinum-treated mACC. TRIAL REGISTRATION: Clinicaltrials.gov NCT01772004; registered January 21, 2013. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-018-0424-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6198369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61983692018-10-30 Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial Le Tourneau, Christophe Hoimes, Christopher Zarwan, Corrine Wong, Deborah J. Bauer, Sebastian Claus, Rainer Wermke, Martin Hariharan, Subramanian von Heydebreck, Anja Kasturi, Vijay Chand, Vikram Gulley, James L. J Immunother Cancer Research Article BACKGROUND: We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC). METHODS: In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received avelumab at 10 mg/kg intravenously every 2 weeks. Continuation of mitotane was permitted; however, mitotane levels during the study were not recorded. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors v1.1. RESULTS: Fifty patients received avelumab and were followed for a median of 16.5 months. Prior treatment included ≥2 lines in 74.0%; mitotane was continued in 50.0%. The objective response rate (ORR) was 6.0% (95% CI, 1.3% to 16.5%; partial response in 3 patients). Twenty-one patients (42.0%) had stable disease as best response (disease control rate, 48.0%). Median progression-free survival was 2.6 months (95% CI, 1.4 to 4.0), median overall survival (OS) was 10.6 months (95% CI, 7.4 to 15.0), and the 1-year OS rate was 43.4% (95% CI, 27.9% to 57.9%). In evaluable patients with PD-L1+ (n = 12) or PD-L1− (n = 30) tumors (≥5% tumor cell cutoff), ORR was 16.7% vs 3.3% (P = .192). Treatment-related adverse events (TRAEs) occurred in 82.0%; the most common were nausea (20.0%), fatigue (18.0%), hypothyroidism (14.0%), and pyrexia (14.0%). Grade 3 TRAEs occurred in 16.0%; no grade 4 to 5 TRAEs occurred. Twelve patients (24.0%) had an immune-related TRAE of any grade, which were grade 3 in 2 patients (4.0%): adrenal insufficiency (n = 1), and pneumonitis (n = 1). CONCLUSIONS: Avelumab showed clinical activity and a manageable safety profile in patients with platinum-treated mACC. TRIAL REGISTRATION: Clinicaltrials.gov NCT01772004; registered January 21, 2013. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-018-0424-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-22 /pmc/articles/PMC6198369/ /pubmed/30348224 http://dx.doi.org/10.1186/s40425-018-0424-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Le Tourneau, Christophe Hoimes, Christopher Zarwan, Corrine Wong, Deborah J. Bauer, Sebastian Claus, Rainer Wermke, Martin Hariharan, Subramanian von Heydebreck, Anja Kasturi, Vijay Chand, Vikram Gulley, James L. Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial |
title | Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial |
title_full | Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial |
title_fullStr | Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial |
title_full_unstemmed | Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial |
title_short | Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial |
title_sort | avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the javelin solid tumor trial |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198369/ https://www.ncbi.nlm.nih.gov/pubmed/30348224 http://dx.doi.org/10.1186/s40425-018-0424-9 |
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