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Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. METHODS: In a phase 1 trial (JAV...

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Autores principales: Dirix, Luc Y., Takacs, Istvan, Jerusalem, Guy, Nikolinakos, Petros, Arkenau, Hendrik-Tobias, Forero-Torres, Andres, Boccia, Ralph, Lippman, Marc E., Somer, Robert, Smakal, Martin, Emens, Leisha A., Hrinczenko, Borys, Edenfield, William, Gurtler, Jayne, von Heydebreck, Anja, Grote, Hans Juergen, Chin, Kevin, Hamilton, Erika P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807460/
https://www.ncbi.nlm.nih.gov/pubmed/29063313
http://dx.doi.org/10.1007/s10549-017-4537-5
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author Dirix, Luc Y.
Takacs, Istvan
Jerusalem, Guy
Nikolinakos, Petros
Arkenau, Hendrik-Tobias
Forero-Torres, Andres
Boccia, Ralph
Lippman, Marc E.
Somer, Robert
Smakal, Martin
Emens, Leisha A.
Hrinczenko, Borys
Edenfield, William
Gurtler, Jayne
von Heydebreck, Anja
Grote, Hans Juergen
Chin, Kevin
Hamilton, Erika P.
author_facet Dirix, Luc Y.
Takacs, Istvan
Jerusalem, Guy
Nikolinakos, Petros
Arkenau, Hendrik-Tobias
Forero-Torres, Andres
Boccia, Ralph
Lippman, Marc E.
Somer, Robert
Smakal, Martin
Emens, Leisha A.
Hrinczenko, Borys
Edenfield, William
Gurtler, Jayne
von Heydebreck, Anja
Grote, Hans Juergen
Chin, Kevin
Hamilton, Erika P.
author_sort Dirix, Luc Y.
collection PubMed
description PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. METHODS: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). RESULTS: A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). CONCLUSION: Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.
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spelling pubmed-58074602018-02-13 Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study Dirix, Luc Y. Takacs, Istvan Jerusalem, Guy Nikolinakos, Petros Arkenau, Hendrik-Tobias Forero-Torres, Andres Boccia, Ralph Lippman, Marc E. Somer, Robert Smakal, Martin Emens, Leisha A. Hrinczenko, Borys Edenfield, William Gurtler, Jayne von Heydebreck, Anja Grote, Hans Juergen Chin, Kevin Hamilton, Erika P. Breast Cancer Res Treat Clinical Trial PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. METHODS: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). RESULTS: A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). CONCLUSION: Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC. Springer US 2017-10-23 2018 /pmc/articles/PMC5807460/ /pubmed/29063313 http://dx.doi.org/10.1007/s10549-017-4537-5 Text en © The Author(s) 2017 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.
spellingShingle Clinical Trial
Dirix, Luc Y.
Takacs, Istvan
Jerusalem, Guy
Nikolinakos, Petros
Arkenau, Hendrik-Tobias
Forero-Torres, Andres
Boccia, Ralph
Lippman, Marc E.
Somer, Robert
Smakal, Martin
Emens, Leisha A.
Hrinczenko, Borys
Edenfield, William
Gurtler, Jayne
von Heydebreck, Anja
Grote, Hans Juergen
Chin, Kevin
Hamilton, Erika P.
Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study
title Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study
title_full Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study
title_fullStr Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study
title_full_unstemmed Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study
title_short Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study
title_sort avelumab, an anti-pd-l1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b javelin solid tumor study
topic Clinical Trial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807460/
https://www.ncbi.nlm.nih.gov/pubmed/29063313
http://dx.doi.org/10.1007/s10549-017-4537-5
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