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Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase
PURPOSE: Metastatic breast cancer (mBC) remains incurable and is associated with low survival rates. This study assessed the efficacy and safety of liposomal irinotecan in heavily pretreated patients with mBC, with or without active brain metastases (BM). METHODS: Following the dose escalation phase...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921078/ https://www.ncbi.nlm.nih.gov/pubmed/33201358 http://dx.doi.org/10.1007/s10549-020-05995-7 |
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author | Sachdev, Jasgit C. Munster, Pamela Northfelt, Donald W. Han, Hyo Sook Ma, Cynthia Maxwell, Fiona Wang, Tiffany Belanger, Bruce Zhang, Bin Moore, Yan Thiagalingam, Arunthathi Anders, Carey |
author_facet | Sachdev, Jasgit C. Munster, Pamela Northfelt, Donald W. Han, Hyo Sook Ma, Cynthia Maxwell, Fiona Wang, Tiffany Belanger, Bruce Zhang, Bin Moore, Yan Thiagalingam, Arunthathi Anders, Carey |
author_sort | Sachdev, Jasgit C. |
collection | PubMed |
description | PURPOSE: Metastatic breast cancer (mBC) remains incurable and is associated with low survival rates. This study assessed the efficacy and safety of liposomal irinotecan in heavily pretreated patients with mBC, with or without active brain metastases (BM). METHODS: Following the dose escalation phase and determination of recommended phase 2 dose, the expansion phase of this phase I, open-label, non-randomized study, assigned adult women to cohorts based on mBC subtype: cohort 1, hormone receptor +/human epidermal growth factor receptor 2−; cohort 2, triple-negative breast cancer; or cohort 3, any mBC subtype with active BM. Patients received liposomal irinotecan 50 or 70 mg/m(2) free base every 2 weeks. Here, we report secondary outcomes including best overall response (BOR), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). RESULTS: For non-central nervous system (non-CNS) disease across all cohorts (intent-to-treat population, N = 29), the ORR was 34.5% (95% confidence interval: 17.94–54.33), with a BOR of partial response in 10 patients (34.5%), stable disease in five (17.2%), progressive disease in 10 (34.5%); four patients were unevaluable (13.8%). The ORR for the CNS cohort was 30.0% (95% confidence interval: 6.67–65.25) using modified Response Evaluation Criteria in Solid Tumors. Common grade 3 or higher TEAEs were diarrhea (27.6%), nausea (17.2%), fatigue (13.8%), asthenia (10.3%), and hypokalemia (10.3%). Serious treatment-related TEAEs were reported in six patients (20.7%). No treatment-related TEAEs resulted in death. CONCLUSIONS: Liposomal irinotecan monotherapy demonstrated antitumor activity in heavily pretreated patients with mBC, with or without BM. The observed safety profile was consistent with that in previous studies. Clinical trial registration: Trial registration ID NCT01770353. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-020-05995-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7921078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-79210782021-03-19 Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase Sachdev, Jasgit C. Munster, Pamela Northfelt, Donald W. Han, Hyo Sook Ma, Cynthia Maxwell, Fiona Wang, Tiffany Belanger, Bruce Zhang, Bin Moore, Yan Thiagalingam, Arunthathi Anders, Carey Breast Cancer Res Treat Clinical Trial PURPOSE: Metastatic breast cancer (mBC) remains incurable and is associated with low survival rates. This study assessed the efficacy and safety of liposomal irinotecan in heavily pretreated patients with mBC, with or without active brain metastases (BM). METHODS: Following the dose escalation phase and determination of recommended phase 2 dose, the expansion phase of this phase I, open-label, non-randomized study, assigned adult women to cohorts based on mBC subtype: cohort 1, hormone receptor +/human epidermal growth factor receptor 2−; cohort 2, triple-negative breast cancer; or cohort 3, any mBC subtype with active BM. Patients received liposomal irinotecan 50 or 70 mg/m(2) free base every 2 weeks. Here, we report secondary outcomes including best overall response (BOR), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). RESULTS: For non-central nervous system (non-CNS) disease across all cohorts (intent-to-treat population, N = 29), the ORR was 34.5% (95% confidence interval: 17.94–54.33), with a BOR of partial response in 10 patients (34.5%), stable disease in five (17.2%), progressive disease in 10 (34.5%); four patients were unevaluable (13.8%). The ORR for the CNS cohort was 30.0% (95% confidence interval: 6.67–65.25) using modified Response Evaluation Criteria in Solid Tumors. Common grade 3 or higher TEAEs were diarrhea (27.6%), nausea (17.2%), fatigue (13.8%), asthenia (10.3%), and hypokalemia (10.3%). Serious treatment-related TEAEs were reported in six patients (20.7%). No treatment-related TEAEs resulted in death. CONCLUSIONS: Liposomal irinotecan monotherapy demonstrated antitumor activity in heavily pretreated patients with mBC, with or without BM. The observed safety profile was consistent with that in previous studies. Clinical trial registration: Trial registration ID NCT01770353. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-020-05995-7) contains supplementary material, which is available to authorized users. Springer US 2020-11-17 2021 /pmc/articles/PMC7921078/ /pubmed/33201358 http://dx.doi.org/10.1007/s10549-020-05995-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Clinical Trial Sachdev, Jasgit C. Munster, Pamela Northfelt, Donald W. Han, Hyo Sook Ma, Cynthia Maxwell, Fiona Wang, Tiffany Belanger, Bruce Zhang, Bin Moore, Yan Thiagalingam, Arunthathi Anders, Carey Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase |
title | Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase |
title_full | Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase |
title_fullStr | Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase |
title_full_unstemmed | Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase |
title_short | Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase |
title_sort | phase i study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase |
topic | Clinical Trial |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921078/ https://www.ncbi.nlm.nih.gov/pubmed/33201358 http://dx.doi.org/10.1007/s10549-020-05995-7 |
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