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Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial
PURPOSE: Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain meta...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543189/ https://www.ncbi.nlm.nih.gov/pubmed/28612225 http://dx.doi.org/10.1007/s10549-017-4304-7 |
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author | Cortés, Javier Rugo, Hope S. Awada, Ahmad Twelves, Chris Perez, Edith A. Im, Seock–Ah Gómez-Pardo, Patricia Schwartzberg, Lee S. Diéras, Veronique Yardley, Denise A. Potter, David A. Mailliez, Audrey Moreno-Aspitia, Alvaro Ahn, Jin-Seok Zhao, Carol Hoch, Ute Tagliaferri, Mary Hannah, Alison L. O’Shaughnessy, Joyce |
author_facet | Cortés, Javier Rugo, Hope S. Awada, Ahmad Twelves, Chris Perez, Edith A. Im, Seock–Ah Gómez-Pardo, Patricia Schwartzberg, Lee S. Diéras, Veronique Yardley, Denise A. Potter, David A. Mailliez, Audrey Moreno-Aspitia, Alvaro Ahn, Jin-Seok Zhao, Carol Hoch, Ute Tagliaferri, Mary Hannah, Alison L. O’Shaughnessy, Joyce |
author_sort | Cortés, Javier |
collection | PubMed |
description | PURPOSE: Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. METHODS: The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician’s choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. RESULTS: In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P < 0.01) versus TPC; median OS was 10.0 and 4.8 months, respectively. Improvement in OS was observed in both poorer and better GPA prognostic groups. Survival rates at 12 months were 44.4% for EP versus 19.4% for TPC. Consistent with the overall BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). CONCLUSIONS: The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-017-4304-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5543189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-55431892017-08-17 Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial Cortés, Javier Rugo, Hope S. Awada, Ahmad Twelves, Chris Perez, Edith A. Im, Seock–Ah Gómez-Pardo, Patricia Schwartzberg, Lee S. Diéras, Veronique Yardley, Denise A. Potter, David A. Mailliez, Audrey Moreno-Aspitia, Alvaro Ahn, Jin-Seok Zhao, Carol Hoch, Ute Tagliaferri, Mary Hannah, Alison L. O’Shaughnessy, Joyce Breast Cancer Res Treat Clinical Trial PURPOSE: Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. METHODS: The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician’s choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. RESULTS: In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P < 0.01) versus TPC; median OS was 10.0 and 4.8 months, respectively. Improvement in OS was observed in both poorer and better GPA prognostic groups. Survival rates at 12 months were 44.4% for EP versus 19.4% for TPC. Consistent with the overall BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). CONCLUSIONS: The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-017-4304-7) contains supplementary material, which is available to authorized users. Springer US 2017-06-13 2017 /pmc/articles/PMC5543189/ /pubmed/28612225 http://dx.doi.org/10.1007/s10549-017-4304-7 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 Cortés, Javier Rugo, Hope S. Awada, Ahmad Twelves, Chris Perez, Edith A. Im, Seock–Ah Gómez-Pardo, Patricia Schwartzberg, Lee S. Diéras, Veronique Yardley, Denise A. Potter, David A. Mailliez, Audrey Moreno-Aspitia, Alvaro Ahn, Jin-Seok Zhao, Carol Hoch, Ute Tagliaferri, Mary Hannah, Alison L. O’Shaughnessy, Joyce Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial |
title | Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial |
title_full | Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial |
title_fullStr | Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial |
title_full_unstemmed | Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial |
title_short | Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial |
title_sort | prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase iii beacon trial |
topic | Clinical Trial |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543189/ https://www.ncbi.nlm.nih.gov/pubmed/28612225 http://dx.doi.org/10.1007/s10549-017-4304-7 |
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