Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial
Abstract Background In this prospective phase 2 trial, we assessed the efficacy of trastuzumab-emtansine (T-DM1) in HER2-negative metastatic breast cancer (MBC) patients with HER2-positive CTC. Methods Main inclusion criteria for screening were as follows: women with HER2-negative MBC treated with ≥...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-019-1215-z |
| _version_ | 1818419282998984704 |
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| author | William Jacot Paul Cottu Frederique Berger Coraline Dubot Laurence Venat-Bouvet Alain Lortholary Hugues Bourgeois Marc Bollet Veronique Servent Elisabeth Luporsi Marc Espié Severine Guiu Veronique D’Hondt Veronique Dieras Marie-Paule Sablin Etienne Brain Souhir Neffati Jean-Yves Pierga Francois-Clement Bidard |
| author_facet | William Jacot Paul Cottu Frederique Berger Coraline Dubot Laurence Venat-Bouvet Alain Lortholary Hugues Bourgeois Marc Bollet Veronique Servent Elisabeth Luporsi Marc Espié Severine Guiu Veronique D’Hondt Veronique Dieras Marie-Paule Sablin Etienne Brain Souhir Neffati Jean-Yves Pierga Francois-Clement Bidard |
| author_sort | William Jacot |
| collection | DOAJ |
| description | Abstract Background In this prospective phase 2 trial, we assessed the efficacy of trastuzumab-emtansine (T-DM1) in HER2-negative metastatic breast cancer (MBC) patients with HER2-positive CTC. Methods Main inclusion criteria for screening were as follows: women with HER2-negative MBC treated with ≥ 2 prior lines of chemotherapy and measurable disease. CTC with a HER2/CEP17 ratio of ≥ 2.2 by fluorescent in situ hybridization (CellSearch) were considered to be HER2-amplified (HER2 amp ). Patients with ≥ 1 HER2 amp CTC were eligible for the treatment phase (T-DM1 monotherapy). The primary endpoint was the overall response rate. Results In 154 screened patients, ≥ 1 and ≥ 5 CTC/7.5 ml of blood were detected in N = 118 (78.7%) and N = 86 (57.3%) patients, respectively. ≥1 HER2 amp CTC was found in 14 patients (9.1% of patients with ≥ 1 CTC/7.5 ml). Among 11 patients treated with T-DM1, one achieved a confirmed partial response. Four patients had a stable disease as best response. Median PFS was 4.8 months while median OS was 9.5 months. Conclusions CTC with HER2 amplification can be detected in a limited subset of HER2-negative MBC patients. Treatment with T-DM1 achieved a partial response in only one patient. Trial registration NCT01975142, Registered 03 November 2013 |
| first_indexed | 2024-12-14T12:36:06Z |
| format | Article |
| id | doaj.art-eb8133670a8c471b9655035877df2e22 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-14T12:36:06Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-eb8133670a8c471b9655035877df2e222022-12-21T23:01:02ZengBMCBreast Cancer Research1465-542X2019-11-012111910.1186/s13058-019-1215-zActionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trialWilliam Jacot0Paul Cottu1Frederique Berger2Coraline Dubot3Laurence Venat-Bouvet4Alain Lortholary5Hugues Bourgeois6Marc Bollet7Veronique Servent8Elisabeth Luporsi9Marc Espié10Severine Guiu11Veronique D’Hondt12Veronique Dieras13Marie-Paule Sablin14Etienne Brain15Souhir Neffati16Jean-Yves Pierga17Francois-Clement Bidard18Department of Medical Oncology, Institut du Cancer de MontpellierDepartment of Medical Oncology, Institut Curie, PSL Research UniversityBiometry and Clinical Trial Promotion Units, Institut Curie, PSL Research UniversityDepartment of Medical Oncology, Institut Curie, PSL Research UniversityDepartment of Medical Oncology, Centre Hospitalier UniversitaireDepartment of Medical Oncology, Centre Catherine de SienneDepartment of Medical Oncology, Clinique Victor HugoDepartment of Radiation Therapy, Clinique HartmannDepartment of Medical Oncology, Centre Oscar LambretDepartment of Medical Oncology, Institut de Cancérologie de LorraineDepartment of Medical Oncology, Hôpital Saint LouisDepartment of Medical Oncology, Institut du Cancer de MontpellierDepartment of Medical Oncology, Institut du Cancer de MontpellierDepartment of Medical Oncology, Institut Curie, PSL Research UniversityDepartment of Medical Oncology, Institut Curie, PSL Research UniversityDepartment of Medical Oncology, Institut Curie, PSL Research UniversityBiometry and Clinical Trial Promotion Units, Institut Curie, PSL Research UniversityDepartment of Medical Oncology, Institut Curie, PSL Research UniversityDepartment of Medical Oncology, Institut Curie, PSL Research UniversityAbstract Background In this prospective phase 2 trial, we assessed the efficacy of trastuzumab-emtansine (T-DM1) in HER2-negative metastatic breast cancer (MBC) patients with HER2-positive CTC. Methods Main inclusion criteria for screening were as follows: women with HER2-negative MBC treated with ≥ 2 prior lines of chemotherapy and measurable disease. CTC with a HER2/CEP17 ratio of ≥ 2.2 by fluorescent in situ hybridization (CellSearch) were considered to be HER2-amplified (HER2 amp ). Patients with ≥ 1 HER2 amp CTC were eligible for the treatment phase (T-DM1 monotherapy). The primary endpoint was the overall response rate. Results In 154 screened patients, ≥ 1 and ≥ 5 CTC/7.5 ml of blood were detected in N = 118 (78.7%) and N = 86 (57.3%) patients, respectively. ≥1 HER2 amp CTC was found in 14 patients (9.1% of patients with ≥ 1 CTC/7.5 ml). Among 11 patients treated with T-DM1, one achieved a confirmed partial response. Four patients had a stable disease as best response. Median PFS was 4.8 months while median OS was 9.5 months. Conclusions CTC with HER2 amplification can be detected in a limited subset of HER2-negative MBC patients. Treatment with T-DM1 achieved a partial response in only one patient. Trial registration NCT01975142, Registered 03 November 2013http://link.springer.com/article/10.1186/s13058-019-1215-zCirculating tumor cellsMetastatic breast cancerHER2Trastuzumab-emtansineLiquid biopsy |
| spellingShingle | William Jacot Paul Cottu Frederique Berger Coraline Dubot Laurence Venat-Bouvet Alain Lortholary Hugues Bourgeois Marc Bollet Veronique Servent Elisabeth Luporsi Marc Espié Severine Guiu Veronique D’Hondt Veronique Dieras Marie-Paule Sablin Etienne Brain Souhir Neffati Jean-Yves Pierga Francois-Clement Bidard Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial Breast Cancer Research Circulating tumor cells Metastatic breast cancer HER2 Trastuzumab-emtansine Liquid biopsy |
| title | Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial |
| title_full | Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial |
| title_fullStr | Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial |
| title_full_unstemmed | Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial |
| title_short | Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial |
| title_sort | actionability of her2 amplified circulating tumor cells in her2 negative metastatic breast cancer the circe t dm1 trial |
| topic | Circulating tumor cells Metastatic breast cancer HER2 Trastuzumab-emtansine Liquid biopsy |
| url | http://link.springer.com/article/10.1186/s13058-019-1215-z |
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